key: cord- -oatjcmy authors: arata, andrew a. title: old and new pestilences date: journal: understanding the global dimensions of health doi: . / - - - _ sha: doc_id: cord_uid: oatjcmy a. “any fatal epidemic disease, affecting man or beast, and destroying many victims.” the oxford universal dictionary, (rd) edition, , oxford press, pp. b. “a contagious or infectious epidemic disease that is virulent and devastating.” webster’s seventh new collegiate dictionary, . g. & c. merriam co., springfield, mass., pp. accordingly, a pestilence should be an infectious disease, devastating (killing) a large number of people (or animals). there has been much popular interest in, as well as technical concern over, newly emerging diseases, and there is a fear that heretofore unknown virulent pathogens will create new, global epidemics. at the time of this writing, two such pathogens are active, warranting such concern: a) cases of sars (severe acute respiratory syndrome, caused by a coronavirus) appeared in china in november, , and has spread to western and central europe and north america; b) a strain of avian influenza virus (n h ), first identified in hong kong in , reemerged in in southeast asia. other avian flu strains found simultaneously in poultry in north america have underscored the concern of local and international health authorities. both sars and avian flu demonstrate high mortality rates, but, to date, the number of cases has been only in the hundreds. so, are these pestilences? what constitutes a pestilence? is the term synonymous with newly emerging diseases? two definitions of pestilence have near unanimity, but are not very specific: a) "any fatal epidemic disease, affecting man or beast, and destroying many victims." the oxford universal dictionary, rd edition, , oxford press, pp. b) "a contagious or infectious epidemic disease that is virulent and devastating." webster' s seventh new collegiate dictionary, . g. & c. merriam co., springfield, mass., pp. accordingly, a pestilence should be an infectious disease, devastating (killing) a large number of people (or animals). the truly epidemic diseases are usually of viral or bacterial origin (although we will make a case for some other types of pestilences). the classification of that may have been bubonic plague continuing until a.d. ). the "black death" of the fourteenth century, which continued to appear in chronic pockets of europe and the middle and near east for centuries thereafter, is by far the best-known plague, and the one that produced the greatest mortality and social impact on the affected populations. consider that as a conservative estimate, − % of the european population died, and maybe more. this death rate reduced the available work force so that, for the first time, peasants and landless people could sell their labor, which introduced freedom of movement and resulted in economic changes that eventually contributed to the decline of the feudal system. the rd pandemic of plague began in the s and continues to this date, although reduced in more recent years. a major characteristic of this epidemic has been the dissemination of plague from its traditional homes in africa and asia into areas previously plague free, especially north and south america, by the inadvertent transport of rats and their fleas by boat. the infection is now well established in africa (gerbils); central asia (gerbils, ground squirrels or "susliks," and marmots); southeast asia (various rattus species); north america (ground squirrels and some native field mice); and south america (introduced rattus). the last major urban outbreak was in surat, india in : more than , cases and deaths were reported. however, the impact of this outbreak was also seen in the number of people who fled the plague zone, and the over two billion dollar loss that ensued. only a few outbreaks are reported to who each year. indochina and burma frequently report, as well as sites in africa (ovamboland on the frontier between namibia and angola); the united states has a vast infected area in the west of the country, but only - cases per year are reported, with - deaths on average every years. many other sites of infection are known and should be monitored, as some rodent species are highly susceptible to serving as effective amplifying reservoirs, whereas others maintain low-level infections for long periods of time, allowing much time to pass between outbreaks. environmental measures (rat-proofing, rodent and flea control, etc.,) are the first measures of control. surveillance, prompt diagnosis, and treatment with antibiotics (e.g., streptomycin and tetracycline) are recommended. yellow fever is the best known of the arboviral (arthropod-borne virus) diseases. there are some known arboviruses, of which about , produce disease in man. both the yellow fever virus and the primary mosquito vector, aedes aegypt, are of african origin -the species name, 'aegypti,' refers to classical africa in general, not, specifically, modern egypt. most cases in africa occur east to west along the transition zone (ecotone) between the savannas and the rain forests inhabited by numerous aedine vectors as well as a. aegypti. the disease has two cycles: a 'jungle' cycle involving various tree dwelling mosquitoes and nonhuman primates as reservoirs, and an 'urban' cycle, with a. aegypti as the vector and humans as reservoirs. the last reported major african outbreak vectored by a. aegypti occurred in nigeria and involved some , cases and over , deaths between and . yellow fever was introduced into the americas one or more times most likely during the age of sail: the virus can be transmitted vertically (transovarian passage) in a. aegypti. the mosquito' s eggs can easily be laid in water barrels and withstand desiccation for months, only to hatch and develop when submersed at a later date. epidemics of yf raged throughout the caribbean and tropical america until the end of the s, when the transmission cycle was elucidated by the team led by walter reed, confirming the role of a. aegypti which had been proposed by, but not confirmed by, carlos finlay. epidemics occurred as far north as philadelphia in the united states and the last epidemic in north america occurred in new orleans as late as , with over , deaths. cases (with - %) mortality continue to occur sporadically in brazil and in the foothills of several andean countries (bolivia, peru, ecuador, and colombia) . often the victims are young, indigenous males from the highlands who were temporarily working in the coca processing plants in the forests. these infected areas are only kilometers from large cities (with populations of more than million people) such as santa cruz, bolivia, which are accessible by public transportation and are heavily infested with a. aegypti. although the yf vaccine is one of the oldest, safest, and most effective available, and immunological protection is rated for at least years, vaccination coverage in many of the affected areas of africa and south america is low. the cholera pathogen, vibrio cholera, originally described by robert koch, was one of the first human pathogens (along with anthrax and tuberculosis) to be identified, in the late s, shortly after pasteur' s publication of the "germ theory." koch and his students studied material they collected in alexandria, egypt, during an outbreak. it was difficult to determine the origin of cholera and/or to distinguish it historically from other diarrhetic diseases except by the severity and rapidity of onset. health historians such as mcneill suggest an origin on the indian sub-continent, associated with dense populations, poor hygiene, and certain religious practices such as communal bathing; thus the term "asiatic cholera," by which the disease became known in europe in the s. the disease' s appearance in europe and the americas (london and new york in , and again in ) were clearly associated with intercontinental traffic. it was during the epidemic in london that a physician, john snow, noted the clustering of cases and deaths in people using the same water source, and proposed what turned out to be the correct action to stop the epidemic ("take the handle off the broad street pump!!"), although he had no idea of the actual cause of the disease. however, it was such observations, along with structural, hygienic, and administrative changes in major cities, particularly in europe and north america, that established the public health measures that we tend to take for granted in this early part of the st century. cholera is still with us: various serotypes of the vibrio have spread since the early s, affecting over countries in asia, in the americas, and into the west pacific. in , approximately , cases and , deaths from cholera were reported. in , the el tor strain of cholera was reported in lima, peru; by , almost a million cases had been reported in the western hemisphere. measles is one of the oldest known and most widespread infections of man: epidemics ascribed to measles appear in the oldest literature, although they are often confused with smallpox. however, in a.d., ad ahrun, a christian priest living in alexandria, egypt, described the pox lesion, and in a.d. the arab physician al-razi distinguished between the two diseases. prior to widespread immunization, measles was common in childhood-more than % of people were infected by age . although endemic in large communities, measles became epidemic every several years, with the severity of infection decreasing with the frequency of the epidemics. in his study of the history of plagues, mcneill makes mention of the importance of animal husbandry and zoonotic diseases in the area. measles, he claims is probably related to both rinderpest (in hoofed-mammals) and canine distemper. because dogs, sheep, and goats have been domesticated for at least , years, measles may have been among the first viral diseases to have "jumped the species barrier." as we will see, most, if not all, of the new pestilences are, or may be, derived from animal wild or domesticated reservoirs. measles was responsible for (or contributed to, along with smallpox) the decimation of the indigenous amerindian populations, first in central and south america at the time of the spanish conquest ( s), and later ( s and s), in north america. amerindian populations lacked immunological protection from these and other imported infectious diseases. some attribute this immunological naïveté to the comparatively small number of domesticated animal species-dogs, ducks and turkeys, guinea pigs, and cameloids (llamas and relatives) in the andes, and few, if any, in large number prior to the european invasion. in any case, the attack and mortality rates were staggering. by one estimate, a pre-conquest amerindian population of perhaps thirty million by was reduced by %, down to only million. this catastrophe occurred in less than years after the spanish entered the american mainland. influenza is another viral disease that has many unstable varieties infecting a host of mammalian and avian species, both wild (sylvatic) and domestic. epidemics with symptoms similar to modern influenza were noted by hippocrates as early as b.c., and later, in rome, by livy. various medieval and renaissance writings describe influenza-like illnesses. robert johnson of philadelphia is credited with the first "modern" description of an influenza epidemic, which occurred in that city in . his description was applied to subsequent epidemics in , , , - , and . antigenic shifts in the structure of the influenza virus may change the virulence of the strains, increasing the likelihood of epidemics. the most severe flu epidemic ever recorded ( ) ( ) -also known as the spanish flu (although it did not originate there)-first struck world war i troops of all combatant nations while in northern france, and it continued on to become a global pandemic. conservative estimates of mortality range between twenty and forty million persons, and other estimates more than double these figures. the ease with which the various influenza strains infect domestic mammals, pigs, and poultry (chickens and ducks) producing huge reservoirs of potentially infectious material, often proximate to human habitations, is a major public health concern. especially worrisome are the conditions under which millions of such animals are raised and brought to market. the 'old' diseases examined above are only a few of those which might be used as examples of the old pestilences: others might prefer to include schistosomiasis, typhus (murine and/or louse-borne), and several of the classic childhood diseases (diptheria, pertussis, tetanus, rubella), as well as leprosy, yaws, the leishmaniases, and, certainly, smallpox. fortunately many of those mentioned here (schisto and others) are being controlled rather well in some areas by vaccines, specific drugs, and/or antibiotics when applicable, at least in the more developed countries. even polio, which had been a major epidemic threat for centuries, has been virtually eliminated as a threat in areas where the politics and health infrastructure allow the efficient application of this very effective vaccine. much of the fear engendered by specific diseases depends on the time, place, and severity of the local outbreaks, as well as the knowledge and perception of the community. for example, i was raised in new orleans, in the southeast of the united states, during the s. although i and my brothers were normal, well nourished children, our parents were fearful of dogs (rabies), cuts on unshod feet (tetanus), and any summer colds or stiffness/weakness of the extremities (polio), and they preached cleanliness as a means to prevent anything bad happening. these diseases are old, but at present each has developed certain new characteristics that make their modern expression different from their historic ones, and decreases our ability to control them. in the last years, malaria parasites have developed resistance to chloroquine, the most common, globally used anti-malarial drug; at the same time, the anopheline mosquito vectors of malaria have progressively developed a parallel resistance to the insecticides used to control them. dengue, and dengue hemorrhagic fever (dhf), have spread globally, infecting vast new areas, especially urban areas where the human living conditions are substandard, but readily suited for vector breeding. finally, tuberculosis, whose incidence was slowly reduced in the late s and early s by improved public health, housing conditions, and nutrition, has again surfaced as a secondary infection to immuno-compromised persons, especially those suffering from hiv infections. at the same time, the causative agent, mycobacterium tuberculosis, continues to develop resistance to the most economic and readily available antibiotics. malaria is caused by blood parasites of the genus plasmodium and vectored by anopheline mosquitoes. there are four species of human malaria parasites: p. falciparum, p. malariae, p. vivax, and p. ovale, as well as a number of related species infecting other mammals (non-human primates, rodents, etc.). historians note that malaria-like symptoms were discussed in the chinese canon of medicine ( b.c.) and malaria-like illnesses were described in th -century b.c. cuneiform literature from nineveh (now part of iraq). hippocrates made a connection between stagnant water and fevers in the local population. it is estimated that there are still several hundred million unreported cases each year resulting in - million deaths per annum, mostly children. although malaria is still endemic in asia, latin america, and africa, % of the cases are found in africa, where p. falciparum is the most common malaria parasite. such huge figures mask the focal, and sometimes epidemic, nature of malaria, which may be brought about by natural or man-made environmental conditions. some of the human activities that may enhance malaria transmission may be development projects for agriculture (e.g., irrigation schemes), other water and land use projects (as in the amazon basin, converting forest areas through resource extraction such as mining and logging) into marginal livestock and farming areas. often such environmental changes bring about changes in malaria transmission from 'stable' (endemic) to 'unstable' (epidemic). in highly endemic areas, severe malaria and death is concentrated in the younger age groups, whereas in the areas of unstable (epidemic) transmission, severe malaria and death is more evenly distributed throughout all age groups. needless to say, prevention and /or case control strategies must be different for each transmission type. in many parts of the world the anopheline vectors of malaria have developed resistance to the insecticides used for their control. frequently, this is due to the use, often excessive, of the same or similar insecticides for control of agricultural pests in the same geographic areas. such resistance not only hinders control operations directly, but also indirectly, by increasing the need for greater quantities and/or more costly insecticides. broadscale usage of insecticides has also become limited on environmental grounds, because some donors have reduced funding insecticide purchases. by far the most serious setback to malaria control in recent decades has been the emergence and spread of chloroquine-resistant strains of p. falciparum, the causative agent of the most severe form of malaria, and the most common in africa. emerging in the s in southeast asia and south america, resistance spread rapidly from these focal points. it was not noted in africa until - but spread rapidly in the ensuing ten-fifteen years. chloroquine-resistant strains of p. vivax have been identified in some areas of southeast asia, new guinea, and indonesia. efforts to produce a malaria vaccine(s) have been under way for over years. a number of candidate vaccines have been produced, but none are operational in humans as yet. like yellow fever, described earlier, dengue and dengue hemorrhagic fever are vector-borne diseases transmitted (primarily but not exclusively) by the mosquito aedes aegypti. "classical" dengue is caused by infection with one of the four serotypes of the dengue virus. dhf may occur following a subsequent infection with a different serotype. the following quotation is from an article written by the author in (r. lennox and a. arata, dengue fever: an environmental plague for the new millennium. capsule report, environmental health project/usaid. pp.): with . billion people at risk and estimated cases in the tens of milllions, dengue is considered by many to be the second most important vector-borne disease in the world (surpassed only by malaria). classical dengue and its more lethal form, dengue hemorrhagic fever (dhf), now circle the world with endemic illness and continuing threats of epidemics. dengue is very much an environmental disease, affecting urban and periurban settlements in more than countries. it is characterized by seasonal outbreaks of illness carried by mosquitoes that thrive in household containers which collect water (such as flowerpots and washtubs) and in the detritus of human consumption, such as bottles, tin cans, and old bottles. children, specially in asia, are most frequently and seriously affected by the severe form of the infection, dhf. mosquito control is the only effective approach to prevention, although effective case management will reduce mortality. insecticides targeted at larval mosquitoes are effective, but resistance of mosquitoes to affordable and environmentally safe chemicals as well as declining will and infrastructure have all but eliminated this approach in most countries. vaccines are in the pipeline, but a system which could deliver them to half the world' s population is probably at least a decade away. community action-to protect containers from becoming havens for mosquito breeding and to dispose of empty containers and trash, along with surveillance and personal protection-is the best hope for transmission risk reduction. tuberculosis is another ancient disease that has bridged the old to new definition: the tb bacillus, mycobacterium tuberculosis, was among the first to be scientifically identified and described (by robert koch, in ). the disease is transmitted by airborne droplets from people with pulmonary or laryngeal tuberculosis. this mode of transmission is most effective in dense populations, and hence tb became widespread with the development of urban centers in the middle ages (europe), and was very common from the th century until recently in europe. with improvements in housing and nutrition tb rates continued to decline (except for periods of war) until the first half of the th century. at that time, two conditions emerged: the development of multiple drug resistant tb (mdrtb) and the emergence and spread of acquired immune deficiency syndrome (aids) upon which tb is an opportunistic infection. prior to , about % of tb bacilli isolated from patients in the u.s. were resistant to even one antibacterial drug: in , % were resistant to at least one drug, and % were resistant to more than one drug. in the u.s. the cost of treatment of ten cases of mdrtb in texas in was us$ , . who lists tb as one of the major causes of mortality in the world. a new major funding effort (who and world bank and various bilateral donor groups) is focusing on hiv/aids, tb, and malaria as the most serious, and intractable, causes of death. other forms of tb, including non-pulmonary cases and those associated with other species of mycobacterium sp. (e.g. m. bovis), are sporadic, but suggest the possible very early animal origin of the pathogen group. diseases such as chagas disease and schistosomiasis are examples of diseases that do not easily fit the epidemic definitions of a pestilence mentioned earlier in this chapter, but they do heavily impact the affected populations, not only through mortality rates, but especially through morbidity/disability. there are several forms of schistosomiasis caused by different species of schistosoma, a blood fluke (trematode)-this is an ancient illness, known from egyptian antiquity. infections occur in fresh water where people work and/or wash and children play. larval worms, known as cercaria, developed in a snail intermediate host, pass through the skin and penetrate diverse organs according to species. the most important effects are those that arise from chronic, and cumulative, infection. chagas disease has a very different etiology, mode of transmission, and pathology than does schistosomiasis. by definition it could be new because it was first described in by the brazilian carlos chagas, who subsequently described the pathogen, a flagellate protozoan, trypanosoma cruzi, and the vectors, bloodfeeding triatomine bugs. the disease is also know as american trypanosomiasis, and occurs only in the western hemisphere, from mexico to argentina-a few cases have been reported in north america. this form is very different from african trypanosomiasis (sleeping sickness). the initial (acute) phase of the disease usually occurs in children; there is then a long latent phase (∼ years or more), culminating later in life in a chronic phase which may include irreversible cardiac and/or intestinal manifestations and shortened life spans in the victims. paho and who consider chagas disease to be the most serious parasitic disease in latin america and the main cause of heart disease in the region. there is no adequate medical intervention. the infection can be transmitted by vectors, congenitally, or by transfusion of blood or blood products. an estimated million persons in the region are at risk, and in some countries (e.g., bolivia) % of the million inhabitants have been shown to be seropositive. in addition, in bolivia, one study demonstrated that the burden of chagas disease, in terms of disability adjusted life years (dalys), was million dalys, or estimated loss of million bolivianos: equal to more than million us dollars at the time of the report ( ). the purpose of this brief segment is to emphasize that pestilences need not carry with them only high mortality. very high morbidity and sustained disability with all the concurrent social and economic implications can be a tremendous burden on a population-or a nation. puerperal fever, a forgotten pestilence, is caused by a streptococcal infection and is an iatrogenic disease (induced by a physician) that was once the scourge of pregnant women, before physicians learned to wash their hands before examining pregnant women and/or assisting at childbirth. improved hygiene in hospitals was concurrent with the development of the germ theory and mortality rates dropped quickly. this disease, also called childbirth fever, was never reported as one of the great pestilences, however a few figures reveal the state of scientific knowledge regarding any infectious diseases, both endemic and epidemic. it is frightening that not only was the incidence of puerperal fever higher in the hospitals, but so was the associated mortality: % of the patients died if the disease occurred after a home delivery, but - % died if the disease was contracted in a hospital. although we have no crystal ball to predict what, if any, new pestilences are in store for mankind in the future, several groups of zoonotic viruses include likely candidates (table ) . also included is hiv/aids, truly a new pestilence that already, in a relatively brief period, has taken its place among the worst pestilences ever known to man. as mentioned above, there are over arboviruses isolated and characterized-about are capable of infecting humans, from nonapparent infections to very severe ones. two of these have already been mentioned above (dengue and dhf and yellow fever), but the arboviruses as a group represent the source of many potentially new diseases-or, put more correctly, existing zoonotic diseases that emerge when humans accidentally become involved in their cycles. a good example is the recent outbreak of west nile encephilitis in the u.s. in and , the virus was isolated from/around new york city from large numbers of dead birds (especially crows and jays): human cases and two deaths were confirmed. by , the disease moved west toward the mississippi river, infecting people and killing nine. in , there were over , cases ( fatal); by , the virus, and human cases, were found in all contiguous states (excepting alaska and hawaii). the virus has been found in mammals, birds, and mosquitoes throughout the u.s. but is this a new disease, or just a disease new to us? west nile virus has been found in over countries since its discovery in in uganda, and has been most of the above are mosquito-borne, and the major mosquito vector genera, culex, aedes, and anopheles, have global representatives from which a competent vector might be found. the same is true of ticks, sandflies, and other potential vectors. rodents, or other local vertebrates, may serve as reservoir hosts while infected migratory birds may provide distribution of the infection. although many arboviral infections have broadly similar transmission cycles, the ecology and dynamics of each may differ widely. arboviruses do not belong to a single viral family, but rather, to several,which increases their diversification. although the potential for increased arboviral epizootics or epidemics is high, the most recent episodes have not been high on the pestilence scale; rather, the most severe arboviral epidemics have been yf and dengue/dhf, the oldest of the group. the arenaviruses were thought for years to be monotypic, a single species, lymphocytic choriomeningitis (lcm), occurring primarily in the house mouse/ laboratory mouse, mus musculus. the virus (first described in ) has been isolated in numerous locations, but human disease is known only from europe and the americas. a second arenavirus was isolated from a phyllostomatid (fruit-eating) bat from trinidad, but there was no associated human disease. severe hemorrhagic cases in argentina and later in bolivia in the s and s resulted in the discovery of new viruses and diseases in these countries-junin virus/argentine hemorrhagic fever (ahf) and machupo virus/bolivian hemorrhagic fever (bhf). more recently, additional arenaviruses found in brazil (sabia virus) and venezuela (guanarito virus) produce similar hemorrhagic symptoms. ahf is the most common, - , recorded annually between and -the others are only sporadic, but mortality rates are high in all these diseases. in each of these, transmission is by contact with infected rodent excreta, dust, and other substances associated with grain harvesting and storage. there are another five arenaviruses in the americas that are not known to cause any illness in humans or their rodent hosts. all of the rodents associated with these viruses belong to only one of the rodent families currently inhabiting south america. these rodent genera (calomys, sigmodon, oryzomys, et al) , are very closely related, and share a common ancestry. paleontological evidence indicates that the isthmus of panama was a bridge connecting north and south america more than - million years ago, allowing a faunal interchange. the sigmodont rodent progenitors entered south america at that time, and rapidly evolved into the modern genera and species. presumably the "ancestor virus" tagged along, co-evolving into the situation that now exists. by far the most important arenaviral disease is lassa fever: discovered in nigeria in , it is known from african countries, mostly in west and central africa, but also zimbabwe and mozambique. the natural host of lassa virus is the multi-mammate rat, mastomys natalensis, one of the most common and widely distributed african field rats. like their south american counterparts, the ahf and bhf hosts, mastomys, is basically a grassland species, easily adapting to the man-made grasslands of maize, sorghum, millet, sugarcane, and other cultivated grasses. cases of lassa are generally associated with agricultural activities and food storage: transmission is by contact with excreta of infected rodents. without laboratory facilities for confirmation, it is difficult to distinguish lassa fever from ebola, yf, or even severe cases of malaria. there are an estimated , cases a year, with more than % mortality rate in hospitalized cases. the disease is more severe in pregnancy, with fetal mortality reported at more than %. in the early s (and before ebola outbreaks occurred), lassa caused great consternation in europe and the americas over the possibility of introduction of this disease. these concerns still exist and have been heightened after the appearance of these other groups of viral hemorrhagic diseases. the hantaviruses are comprised of two large groups of viruses, all transmitted by rodents and producing a range of hemorrhagic, renal, and/or pulmonary complications. the old world hantaviruses are comprised of over different viruses, several known for some time under a different classification (e.g., hanta virus is the cause of korean hemorrhagic fever with renal syndrome, an important military disease in the s). most cases still occur in agrarian and military populations and occur in over countries in asia, africa, and europe: each year approximately , cases occcur in eurasia, with more than % of these reported in china. case fatalities range from . % to . % depending on the virus. the or so new world hantaviruses produce a pulmonary, rather than a renal, syndrome. since being described as a group in , approximately , cases have been reported in the americas, with a high case fatality rate ( - %). the natural hosts/reservoirs for the hantavirus groups are mostly muroid rodents (old world group), and cricetid rodents (new world group). this is not surprising, as these two are amongst the largest and most widely distributed mammalian families. however, the manner and zones of transmission are similarrodent contamination of grain crops in the field and storage where people come in contact with rodent excreta. the two closely related filoviruses (marburg and ebola) are among the most virulent viruses yet described with an overall fatality rate of more than %, and higher in several outbreaks (possibly augmented by use of dirty syringes and needles to give injectable chloroquine (an anti-malarial drug) to the patient' s friends who carried him/her to the hospital. marburg virus was first described ( ) among monkeys sent from east africa to european laboratories, there killing laboratory technicians. subsequent outbreaks have occurred in africa. ebola virus appeared in in simultaneous outbreaks in zaire (democratic republic of congo). (barry, ) one ebola strain was implicated in an outbreak in an animal holding facility in reston, virginia, u.s.a. several humans seroconverted but showed no disease symptoms. the repeated outbreaks of ebola and marburg virus, mostly in central africa, have been described as commencing with "rapidity and devastation." during an epidemic, transmission is generally by contact with contaminated blood or other tissues from infected persons. most outbreaks have been in rather remote areas with poor health care facilities, so that patients are seen only with advanced symptoms. we have not been able to find reservoir organisms (there have been subsequent, better equipped expeditions than the one described in the footnote, but none have been successful), nor do we know the mechanism(s) of transmission in the wild. one distinct ebola virus strain from ivory coast was isolated from a chimpanzee: primates are hunted and eaten by humans in parts of africa and this may serve as the 'link' at which the virus(es) are able to "cross the species barrier" and enter the human population. (barry, ) the government of sudan requested who assistance, and the government of zaire requested the same from the u.s. government (cdc). representatives of who and cdc met in the next few days at the london school of hygiene and tropical medicine to work out details and coordination (who was represented by dr. paul bres and the author, and cdc by dr. karl johnson). we had all thought of lassa and marburg viral fevers, and were surprised when dr. johnson said it was neither: he then showed us electron photomicrographs of tissue taken from an early case-the stringlike " and " figures were just like marburg. but, he explained, this one was serologically distinct from marburg, and they proposed to name it after a river in the area, the 'ebola'. we agreed that i (aaa) and a virologist (dr. bruce johnson) from the lshtm would go to the site in sudan to sample potential reservoirs and/or vectors. bruce would bring the supplies needed for taking tissue samples and the liquid nitrogen containers needed to return the samples to the uk. i was to gather the animal collecting materials. who had no such equipment in geneva, of course, so i borrowed 'mist' nets for collecting bats from the british musum (natural history) and the museé d' histoire naturelle in geneva and borrowed sample rodent traps from the swiss agricultural research station in nyon, near geneva. we had the traps made in nzara, one of the sites of the outbreak in sudan. to autoclave the dissecting instruments we purchased two household 'pressure cookers' at the local super market (migros) in geneva. placed on stones over an open fire, they served well. an experimental ebola vaccine has been reported to be successful in trials with non-human primates. human trials will be conducted soon. two previously unknown and unrelated human viral infections, severe acute respiratory syndrome (sars) and an asian avian influenza (strain h n ), originating in southeast asia, have received a great deal of popular attention and public health concern. in november , cases of a respiratory illness, subsequently labeled sars, appeared in china. a delay in timely reporting of the initial cases allowed it to spread to other southeast asian countries, australia, the americas, and at least european countries. reports of the actual number of persons infected varied, but cases numbered in the thousands, and mortality rates of up to % were indicated. surveys of wild animals captured for human consumption quickly showed that ferrets, civets (related to mongooses), and raccoon dogs (shaggy fox-like carnivores) were positive for harboring the virus, but it is not known if any of these are the true reservoir in nature. the who has reported that the chain of transmission may have been broken (no new cases reported in a period of time equal to two consecutive day incubation periods). this is clearly a case of a virus "species jumping". in the world' s largest, most densely populated country this could spell disaster, especially if the reporting network is compromised. the asian avian influenza strain initially appeared in poultry in hong kong in , when it jumped the species barrier and killed out of infected persons. this recent outbreak spread to korea (december, ) , then japan and vietnam (january ). hong kong reportedly slaughtered . million chickens and ducks, and as many as three million slaughtered through the southeast asia region, but other reports indicate that there are nonspecific wild variants of this strain in wild birds that serve as natural reservoirs. of major concern is that outbreaks of highly pathogenic avian influenza are increasing in frequency and severity. reportedly, in the years from to , there were only outbreaks, but in the past six years, from to , there have been six, not including the most recent incidents. if bubonic plague was the quintessential pestilence of the ancient and medieval worlds, acquired immunodeficiency syndrome, caused by the human immunodeficiency virus (aids/hiv) is the chief pestilence of the modern world; and it is still growing, not receding. there is also a vast literature that will not be reviewed here, but the following data points describe the severity of the pandemic pestilence: r aids is gaining a firmer foothold in the large populations of india and china; r world wide, million people are infected with hiv; r - million of these infected people live in sub-saharan africa; r million persons became infected this year, , are children; r million persons died of aids this year, , of them less than years old; r existence of simian immunodeficiency virus (siv) suggests animal origin. the social damage accompanying this pandemic is not reflected in the bare figures given above; especially the orphaned children, destroyed family structures, and so forth. it has been estimated that billion dollars us, per annum, is required to provide the prevention and treatment facilities and services needed: to date, less than one-half ($ . billion per annum) has been made available. some of the old category diseases are still strongly with us (e.g., malaria, tb, influenza), and, by adapting traits such as drug-resistance and crossing or jumping species, they expand their reservoir-host base. as such, they could be considered new. some other old diseases are rather well controlled in the developed countries where the surveillance systems are efficient and vaccination and other preventive services are readily available and properly used. these would include smallpox (eradicated), polio (eradicated in some areas), and childhood illnesses such as pertussis, diptheria, tetanus, measles, and so on. even bubonic plague could be characterized as being under control-it is widespread, but also well understood, and with vector control and appropriate antibiotics, outbreaks are not severe and mortality is low. on the other hand, some of the new (most recently discovered) diseases like ebola and hiv/aids are hard to handle. we know little about the natural history of ebola, lassa, or the south american hemorrhagic fevers, and our knowledge of hiv/aids in the laboratory probably exceeds our understanding of the socioeconomic impacts it is having on whole cultures. when lassa virus "jumped" from the field rat, mastomys, to humans it was dreadfully virulent, and it seemed to come from nowhere. but, after a few years, we know that (with one exception from a bat) all arenaviruses are well adapted to particular rodent groups; most rodents are grass eaters, and lots of crops are grasses (wheat, maize, sugarcane, rice, etc.); therefore, the arenaviral fevers are seen primarily in agricultural settings and with stored grain. yet, for the more recently known hantavirus group, or even less with the multiferous arboviruses, we do not have good data on ecological determinents, or even host-reservoir relationships. at the same time, people are modifying environmental conditions rapidly and extensively, and we have little information indicating whether such changes will eliminate potential disease cycles or exacerbate them. this may be even more important for diseases like influenza. if they have obligate or opportunistic vertebrate hosts and these are coincidentily reduced in number or eliminated, what selection pressures are set in action on the virus population to select new hosts? and when it comes to modifying environments, man has no equal. yet we know that this microbial evolution is going on at a rapid pace-just look at how fast drug-resistance develops and spreads! in reading articles and researching references for this document, i was amazed to discover again how many human illnesses have their direct animal (zoonotic) counterparts, or were vectored/hosted by arthropods, rodents, or snails, and how an avian influenza can become a mammalian influenza very quickly, and how a bat or an oppossum can do the same for the chagas disease trypanosome. it is in this context that i feel that we know very little of the natural history or the ecological dynamics of the disease transmission cycles we teach. especially disturbing is to read of a new strain of asian avian influenza and the necessity, around the world, to kill millions of birds. if one was to dream up a model pathogen incubator and dissemination engine, the perfect model would be a modern chicken farm of , birds, defecating as birds do, and that at a constant temperature and with residues of organic chicken feed all about. and we wonder why new diseases emerge? any farmer worth his/her salt knows that monoculture breeds pests. this is a good place to bring up one other difficult subject-bioterrorism. it is difficult for one dedicated to public health principles to imagine why anyone would even consider using infectious diseases as a weapon, but it is being done, and we need to be able to distinguish between a natural epidemic and one orchestrated by man. again, knowledge of the natural history of the organisms, their natural hosts and reservoirs, will help. already the u.s.a. is stockpiling smallpox and anthrax vaccines in large quantities. one final point; most people concerned with new versus old pestilences work as epidemiologists, infectious disease specialists, hospital officials, and so forth. but public health work is broader than the study and treatment of infectious diseases, and the study the global burden of disease, sponsored by the who, world bank, and harvard university, based on measuring dalys, predicts that fewer infectious disease will be as important in the future as they are at present. for example, "the next two decades will see dramatic changes in the health needs of the world' s populations, and non-communicable diseases such as depression and heart disease . . . are replacing the traditional enemies, such as infectious diseases and malnutrition." maybe toxic smog and non-communicable diseases will replace pestilences, both old and new! the great influenza control of communicable diseases manual exotic viral diseases death by migration plague: an ancient disease in the twentieth century (rev emerging infections plagues and people the global burden of disease the doctor's plague viruses, plagues, and history emerging infectious diseases (vol. - ). www.cdc.gov/eid or hard copy from cdc key: cord- -n gk xhb authors: kickbusch, ilona title: policy innovations for health date: - - journal: policy innovation for health doi: . / - - - - _ sha: doc_id: cord_uid: n gk xhb we are at a turning point in health policy. it has become increasingly clear that changes in the existing health care system will not be sufficient to maintain and improve our health at this historical juncture. both our extensive knowledge on what creates health as well as the exponentially rising rates of chronic disease obesity, and mental health problems indicate that we need to shift course and apply a radically new mind-set to health and health policy. this is what we mean by policy innovations for health. the boundaries of what we call the “health system” are becoming increasingly fluid and health has become integral to how we live our everyday life. health itself has become a major economic and social driving force in society. this shifts the pressure for policy innovation from a focus on the existing health system to a reorganization of how we approach health in st century societies. the dynamics of the health society challenge the way we conceptualize and locate health in the policy arena and the mechanisms through which we conduct health policy. they also redefine who should be involved in the policy process. this concern is beginning to be addressed within government through health in all policy approaches and beyond government through new partnerships for health. most importantly, the role of citizen and patient is being redefined – a development that will probably lead to the most significant of the policy innovations for health in the st century. innovation is something everyone wants more of, but nobody is too sure what it means exactly. john gapper [ ] innovation for the authors of this book is about applying a radically new mindset to health and health policy with the goal of addressing the determinants of health and involving citizens in their health in new ways. this explains our choice of terminology: policy innovations for health. we start from a perspective that considers both health and innovation to be central driving forces in st century societies, and we maintain that their prominent role reflects major societal shifts that are under way. the consequence is not only a changing role of health in modern societies but also a new perception of innovation in relation to health. as part of this change we see new mechanisms emerge which aim to address the seminal changes underway in health and society. the shift from the industrial society of the th and th centuries to the knowledge societies of the st century is as ground-breaking as was the shift from the agrarian to the industrial world -and they are similar in their deep impact on health, this increases the need for innovation. the changes in our way of life are shaping our lifestyles and have created a situation where many of the patterns of everyday life -for example, our eating and food shopping patterns -and new forms of social stratification -for example, new forms of social inclusion and exclusion -endanger our health. this means that we need to understand that the health challenges and the diseases that come with this change are of a larger societal, not an individual nature. it seems obvious that this development has two consequences: it changes the role of the health care sector significantly toward managing chronic disease rather than acute care and it moves many of the solutions for the most challenging health problems into other social and policy arenas. the authors of this book are focused on the second challenge and the policy mechanisms that are needed to address it. the need for change is vast. first, there is hardly a policy sector that can be excluded: health, education, agriculture, transport, industry, consumer affairs, and sports -all are essential to support health. second, in a consumer society the role of business is critical and consumers themselves must express their demand. finally, communities must act for their health interest and individuals are required to support their individual health and that of their families in new ways. to do so they need to be able to negotiate and navigate an increasingly complex health and care environment. a recent analysis concerned with innovation and high performing health systems [ ] underlines that there are two goals of innovation in relation to health: improving the affordability, quality, and efficiency of the health care system and improving the health of populations. ideally the two would be fully complementary -in the real world they are not. usually when we speak of innovation in the context of health the automatic assumption is that we mean the expansion of therapeutic possibilities -we associate new medicines, new technologies, and increasingly the potential of biomedicine and genetics. sometimes we think of new approaches to the organization and financing of the medical care system, then we typically speak of "health care reform" -a term that is now linked almost exclusively with efficiency, effectiveness, and cost saving. the words innovation and health policy do not by and large sit very well together because the notion of "newness" and "better" that is at the core of innovation has been overshadowed by many short-term reorganizations of health care systems that seem to lack in vision and long-term perspective. and, if innovation is considered in terms of radical innovation only then we experience a clear tension between the drive for innovation and the constant challenge to keep down health care expenditures. a recent health innovation survey by the oecd [ ] typically focuses on the "question how to encourage and foster innovation which addresses health needs and priorities, maximizes access to benefits, and manages challenges and risks in a way that is beneficial to both innovators and health systems." innovation in this case is also mainly related to innovations in biotechnology and the key challenge is how oecd countries are able to cope with introducing such technical and product-based innovations into their respective health care systems. this focus on financial pressure has led -through a range of new assessment mechanisms -to a reinforcement of a binary understanding of innovation as being either radical or incremental and a focus on medical rather than social value. over the last decade we have begun to witness a major shift with regard to health and its role in society. i argue that we now live in a health society which is characterized by two major social processes: the expansion of the territory of health and the expansion of the reflectivity of health [ ] . the creation of the health society of the st century has been a process long in the making, beginning from about the mid th century onward. health is integral to modernity and our modern societies would not be possible without the health gains achieved in this -year period [ ] . during this time the balance of power between the four domains of the health systempersonal health, public health, medical health, and the health market -has shifted continuously. the domains of personal health and public health dominated the th and th centuries, while during the th century the medical health domain gained increasing strength both in terms of its power over the social definition of health and the dominance of its organizational and governance infrastructure; this process of dominance has been referred to as medicalization. as a consequence, in both political and public perceptions, the social organization of health resides in what we have come to call the health care system and concerns over how to ensure the long-term financial sustainability of this system dominate the health policy debate. but today the boundaries of what we call the "health care system" are becoming increasingly fluid. health has become integral to how we live our everyday life. in this health is similar to innovation, which is also increasingly defined as being fluid, an issue that will be reflected upon later in this chapter. indeed the expansion and liquidity of boundaries is a major characteristic of what the sociologist zygmunt bauman calls "liquid modernity" [ ] . this changes the health policy debate because it means that health is everywhere: every policy decision a government makes also impacts on health and at the individual level every behavioral choice also has a health consequence. this was always the case -but now it is part of reflective modernity. most discussions on health policy do not yet take this deep seminal change into account -they still focus on tinkering with a well-defined functional system of health governance, where through a process of defining the evidence base, they aim to ensure clear boundaries, define interventions, and prioritize medical rather than social solutions. the authors of this book are of the opinion that we clearly need a policy approach that responds more adequately to the new environment of st century health. the dynamics of the health society not only challenge the way we conceptualize and locate health and how we conduct health policy but they also redefine who should be involved in policy making -together they constitute policy innovations for health. the chapters of the book further explore five key defining concepts: . health is more than disease and health outcomes need to be measured differently; . the system boundaries are shifting and organization of health in society is increasingly separated from the management of disease and illness; . health policy is more than health care policy and becomes a joined up process of health in all policies at all levels of governance; . the differentiation into a first and second health market is occurring rapidly and we are faced with new issues of financing both health and health care; . people themselves are major actors in the health arena and new technologies are allowing them to participate in completely new ways. many analysts make the point that the changes facing the health sector will be as phenomenal as those we have witnessed in information technology and communications. this is due to the fact that health itself has become a major economic and social driving force in society [ ] and that good health outcomes are increasingly important for a range of societal goals. the conference board of canada [ ] suggests understanding innovation "as a means by which societies, systems or organizations achieve social or economic value (e.g. increasing positive health outcomes)"; they maintain that innovation occurs only when new value is created. our focus in this book is to explore what kind of policy innovations for health are required to achieve better population health, in terms of both its social and economic value. we argue though that the issue at stake is not just another reorganization/improvement of the health care system or a better mechanism of integrating scientific progress into existing heath care systems but a reorganization of how we approach health in st century societies. in this we follow peter drucker's understanding of innovation as creating a new dimension of performance [ ] . in modern democracies health is considered a right. its doability is driven by the perception that health can be created, managed, and produced: more health is always possible. it is one of the characteristics of the health society that the notion of doability has expanded beyond the ever-rising expectations toward the curative medical care system to impact the determinants of health. the first conceptual starting point for the arguments in this book are the rapidly changing determinants of health. we build on the arguments for increasing the investment for health and well-being and for strengthening the connection between health and wealth which are beginning to be expressed far beyond the public health community. witness the similarity of the statements from the public health perspective as voiced by wilkinson and marmot [ ] , two of the most respected researchers on social determinants of health good health involves reducing levels of educational failure, reducing insecurity and unemployment and improving housing standards. societies that enable all citizens to play a full and useful role in the social, economic and cultural life of their society will be healthier than those where people face insecurity, exclusion and deprivation and as expressed in a recent publication commissioned by the european commission [ ] ...improving the health status of a population can be beneficial for economic outcomes at the individual and the national level. there is indeed much evidence to suggest that the association between economic wealth and health does not run solely from the former to the latter. an immediate, if general, policy implication that derives from this conclusion is that policy-makers who are interested in improving economic outcomes (e.g. on the labour market or for the entire economy) would have good reasons to consider investment in health as one of their options by which to meet their economic objectives. it follows that if societies are to prepare adequately for new health challengessuch as obesity -and if they are to take action on the changes already under way, they must completely rethink their approach to health policy. it is argued that health sustainability is as important as environmental sustainability and that our response must be understood to be the challenge of at least a generation [ ] . we need policy innovations for health that address the classic determinants of health, such as education, work, housing, transport, and particularly equity. some countries -such as sweden -have now done so and this is discussed in more detail in the chapters that follow [ ] . the "classic" determinants of health continue to influence our health. the determinants of health however, in the boundaryless health landscape of the st century policy innovations are called for that respond to the st century determinants of health. health is increasingly being shaped by forces such as the speed of modern societies, globalization of markets, the increasing mobility and insecurity of individuals, energy expenditure, and concerns regarding risk and safety, and the reach of the media. these forces cut across many of the acknowledged social, environmental, and economic determinants of health. an approach to visualize the many determinants and their interaction was developed by the well-being project, scotland, in a joint effort with members of the community [ ] . the second conceptual starting point for the authors of this book is an understanding of health which is social rather than a medical. health governance is now challenged by this conceptualization of health as "well being beyond the absence of disease" as first defined by the world health organization in its constitution [ ] . the ottawa charter of the who [ ] stated that "health is created in the context of everyday life -where people live, love, work, learn and play," and this has found its expression in a wealth of health promotion activities at organizational, community, and local level. the most well known are the many "settings projects," which aim to create supportive environments for health and encourage people to participate in shaping these settings for everyday life, examples include healthy cities, healthpromoting schools, and healthy workplaces [ ] . indeed they constitute social innovations that spread the new understanding of health into many different sectors and, as an activity in the space between the sectors, prepare the ground for policy innovations and their social acceptance [ ] . recent global happiness surveys have identified health next to wealth and education as one of the three key factors for societal well-being [ ] . health becomes more central for the aspiration of personal goals in life and social inequalities are increasingly measured in health terms, highlighting differences in health and life expectancy. this broader view of health also needs to be reflected in the way we measure the impact of policy innovation for health. hernandez-aguada, in his chapter, discusses the increasing relevance of new types of health intelligence for intersectoral health governance with a particular focus on transparency and accountability for all actors in society. one such example of measurement, the canadian index of well-being [ ] , clearly illustrates the dimensions of innovation that a new type of health policy needs to address: • build a foundation to articulate a shared vision of what really constitutes sustainable well-being; • measure national progress toward, or movement away from, achieving that vision; • understand and promote awareness of why society is moving in the direction it is moving; • stimulate discussion about the types of policies, programs, and activities that would move us closer and faster toward achieving well-being; • give canadians tools to promote well-being with policy shapers and decision makers; • inform policy by helping policy shapers and decision makers to understand the consequences of their actions for canadian well-being; • empower canadians to compare their well-being both with others within canada and those around the world; and, • add momentum to the global movement for a more holistic way of measuring societal progress. policies must come to terms with the new forces that act to create or compromise health -they must respond to what has been called "the new personal health ecology" where the individuals are subject to a broad range of influences over which they have very little control [ ] . just as cholera was symptomatic for all the dimensions of the rapid urbanization of the th century, obesity is the symbolic disease of our global consumer society. it will be a test case for the health governance of the st century as was the introduction of water and sewage systems at the end of the th century. such challenges can only be resolved through great political commitment, willingness to innovate, and social action -including social entrepreneurship -at all levels of society. health and innovation are both social constructs, defined by their time and context. just as the concept of health is changing, so is the concept of innovation. the social sciences began in the s to concern themselves with both health and innovation as distinct areas of social analysis. it was at this point that both medical sociology (later to become health and medical sociology) and the sociology of innovation began to advance -the one never far removed from medicine, the other never far from the sociological analysis of technological development. even today much of the literature on innovation still comes from a science and technology perspective. this is in sharp contrast to economics, where already at the beginning of the th century josef schumpeter drew attention to innovation as the engine of social and economic development, highlighting both its power of creation and of destruction [ ] . health has now become such an innovation engine -many investors see health as "the next big thing" and a rapidly growing health market attaches the added value "health" and well-being to an ever-growing set of products and services. the chapter by henke and martin in this book illustrates this process: not only do health innovations change society, but through the societal process of innovation in health the very nature and the characteristics of innovation change, a process that has been described as "the innovation of innovation." this leads further to the concepts of "open innovation" and "fluid innovation," which are discussed further below in relation to policy innovations for health [ ] . in switzerland a recent survey asked a group of health experts to identify the key technological and social drivers of innovation in health [ ] . in the first category the experts established a ranking in the following order: ( ) developments in biotechnology and genetics, ( ) medical technology, ( ) informatics and soft ware, ( ) organic chemistry, ( ) telecommunications and ( ) nano technology. in the second category they ranked ( ) demography, ( ) individual responsibility, ( ) nutrition, ( ) education, and ( ) income distribution. most interesting though -and symptomatic for the speed of social change -is that the experts ranked the social driving forces as more important and forceful than the technological ones. additionally they did not assign a high impact value to political driving forces -which reflects the assumption of the experts, that not much innovation is to be expected from traditional types of health policy. the sociology of innovation argues that innovation itself has become a leitmotif of st century society; this development is called "ubiquitous innovating" [ ] . indeed if one refers to some of the key documents -for example, of the european union or of the oecd -a strategy for innovation is considered essential in order to compete in a global environment [ , ] . it is interesting -with a view to liquid modernity -how similar the discussion of a new conceptualization of innovation is to the discussion on a new understanding of health. health in turn is increasingly seen as one of the cornerstones for competitiveness and innovation. and like innovation it is increasingly seen to be in need of a policy approach that is more concerned with sustainability and long-term effects. the key health sustainability challenges of st century societies are: . the demographic and financial pressure brought to bear on health and social systems through the ageing of societies -societies need to support an increase in healthy life expectancy and an independent life, despite disability and chronic disease; otherwise, we might witness a breakdown of support systems and social solidarities. . in view of new epidemiological developments -for example, the increase of overweight and obesity, early onset of diabetes, and an increase in mental health problems -the generation of children born at the turn of the st century could be the first to have a lower health and life expectancy than their parents. increased investment in the health of the next generation is critical. . health systems organization and financing is not sustainable without major reorientation away from acute care toward increased prevention, management of chronic disease, and community-based, integrated primary health care. . with globalization we are witnessing the rapid spread and emergence of new infectious diseases -such as sars and hiv aids -and the re-emergence of others, such as tuberculosis, there is increasing fear of a global influenza pandemic -increased preparedness is critical at all levels of health governance. . as st century societies are restructuring they are presently witnessing increasing health inequalities -addressing these widening gaps will be a key challenge for trust in modern democracies. . we are only just beginning to understand the health impacts of global warming and climate change -we must be more conscious of the interdependence of health sustainability and environmental sustainability [ ] . while the territory of the medical system can be relatively clearly circumscribed and framed in terms of delivery and utilization of health care services, the territory of health becomes ever less tangible and increasingly virtual. disease has boundaries; health does not. the new health challenges make this blatantly obvious. within government the stakeholders in the response to obesity are not only the health ministry, but, for example, the ministries of transport, education, agriculture, trade, and consumer affairs. outside of government the producers of unhealthy food and drink products are as much in focus as are the settings of everyday life where they are consumed (such as canteens), global marketing and advertising practices, the media messages, and the role model celebrities to name but a few. smoking acts regulate not only who can buy tobacco products, where, and at what price but they define where it is permitted to smoke; in consequence, owners of bars and restaurants, retailers, and the management of airports and railway lines to name but a few, all need to be concerned with health in ways they were not before. consumers and voters as well as a wide array of health action groups and patient organizations make their preferences heard. this infinite nature of health has consequences for all four domains of the health system. it is specific to the health society that all four domainspersonal health, public health, medical health,and the health market -not only continue to change and expand but -and this is critical -that the balance between the systems is shifting [ ] . the health sector -consisting of the public health domain and the medical health domain -struggles to include more health, in the form of strengthening public health, health promotion, and prevention. yet, this approach is falling short in many countries, in particular for lack of political support, except where the measures are clearly medical, such as expanding screening or strengthening predictive medicine. while the new paradigms in preventative medicine are gaining increasing acceptance, public health measures are considered unduly paternalistic and are seen to impinge on the individual freedom of choice. structural measures addressing the determinants are also not politically popular, as they usually impinge on one or the other economic interest. there have been excellent policy documents such as the wanless report in england [ ] that have proposed to embark on an organizational shift within the health sector toward public health, driven in particular by the fear generated by the relentless growth of the medical health domain. they argue that more money needs to be invested in prevention, health promotion, and public health; otherwise, our societies will not be able to afford the constant expansion of the medical health system. so far within the health sector very few policies, institutions, organizations, and funding streams have clearly differentiated between investing for health and the expenditures for providing medical care. durand-zalesky makes this point in great detail in the contribution to this book and she underlines how important the political innovation environment is for a public health agenda focused on determinants -in the case of policy innovation for health the different perceptions of the role of the state, the market and the individuals are critical. where an accounting for health -which is different from the proposed national health accounts -is attempted, countries rarely reach more than a . % average of the overall "health" budget for prevention, health promotion, and public health, as oecd data tell us [ ] . politically the pressure is strong to subject every penny of this paltry amount to critical evidence reviews based on a medical mind-set, while to this day most health service organizations are still not accountable for their health outcomes and demonstrate a severe lack of transparency for patients and consumers. it is therefore arguable whether the expansion of a traditional public health approach -for example, with more funding -will be sufficient. a new nordic initiative argues -as do the authors in this book -that fundamentally new perspectives are needed. they locate them at three levels: mind-set, partnerships, and platforms [ ] . policy innovations for health need to move beyond the established functional boundaries of both the medical health domain and the public health domain. the innovation debate can help in conceptualizing the necessary change. open innovation is a term initially developed for the private sector and championed the idea that companies cannot anymore rely on their own innovative capacity -they need to share and outsource [ ] . the perception of open innovation now means to involve a broad range of partners in order to find innovative solutions, particularly in the form of innovation clusters. as used to be the case in business, the functional and hierarchical approach in the medical and the public health domains do not usually allow for this. there are therefore very few policy mechanisms that allow decision makers to consider both health determinants and health impacts in an integrated manner and to approach the new health challenges with joined up policy responses, initiatives, and interventions. usually each policy (sub) domain works to its own logic and intentions without regard for the impact on other areas of society or its global impact. some exceptions can be found in the area of environmental policies. if -with health in mind -we are willing to see the glass as half full, we can identify a range of policy innovations emerging in health that could be summarized under the term network governance. examples are described in more detail in the chapter by warner in this book. in many countries a first step to engage a broad range of actors around common goals was the development of health targets [ ] , an approach that gained ground from the s onward. in order to achieve the targets it became clear that policies in the health sector needed to be complemented by other sectors of government and that they in turn needed to be supported by policy commitments at different levels of government and in the private and nongovernmental sector. the wanless report calls this the fully engaged scenario [ ] . in consequence a new type of policy mix is emerging between governmental measures, global initiatives, local action, consumer pressure and demand, and mechanisms -such as self-regulation or corporate social responsibility approaches -put into place by companies and the private sector. who would have imagined even a decade ago a range of the policy innovations for health we have witnessed recently: • that a country would base its health policy on the determinants of health as in sweden? • that a health minister would regulate the body mass index of fashion models as in spain? • that television advertising of fast foods to children would be severely restricted as in england? • that a country could accept a total ban on smoking in public places -including restaurants and bars as in ireland? the health society not only means that health is present in every dimension of life, it also implies that risk is everywhere. as every place, setting, product or message in society can support or endanger health the potential stakeholders in any health policy decision expand exponentially; transport policies relate to the obesity epidemic, the beer tax influences young people's alcohol consumption and low literacy increases health inequalities. three types of policy innovations for health that qualify as open innovations are briefly outlined in the following: health in all policies, innovation clusters, and platforms. a key policy innovation for health is the health in all policies approach put forward by the finnish presidency of the european union in [ ] and first developed in the ottawa charter with the term "healthy public policy" [ ] . health in all policies is now also one of the four principles of the european health strategy of the ec [ ] . i have described health in all policies as an innovative policy strategy that responds to the critical role that health plays in the economies and social lives of st century societies. it introduces better health (improved population health outcomes) and closing the health gap as shared goals across all parts of government and addresses complex health challenges through an integrated policy response across portfolios. by incorporating a concern with health impacts into the policy development process of all sectors and agencies, it allows government to address the key determinants of health in a more systematic manner, while taking into account the benefit of improved population health for the goals of other sectors [ ] . some countries have tried to reflect such an approach by creating a ministerial mechanism for the focus on health rather than disease; for example, canada for a while had a minister for public health with cabinet rank, and england and sweden both have junior ministers for health. many partnerships are emerging beyond the health sector and its narrow policy conception. increasingly we see a wide range of innovation clusters developing which create a new type of interface between many different actors following the open innovation model for companies but expanding it into public-private partnerships. one such example "berlin's health care market" is described in this book in more detail by henke and martin. another example is the "myheart" project -which brings partners from countries together to develop "intelligent textiles" in order to prevent heart disease [ ] or the innovations in the area of functional foods. of particular interest as a policy innovation for health is the proposal to establish "the nordic region as a global health lab" [ ] . it is proposed that the nordic countries form an innovation cluster so that the nordic region will become "a global market leader for prevention solutions." they further state that "the booming global market for health related products and services speaks in favor of joint initiatives, where knowledge and experiences produced within a research framework can be used to develop products and solutions attractive to the nordic as well as the global market." they then go on to define the nine components that will give such an initiative a global competitive edge: nine components for success: . a social model supporting equal access to health for all . prevention as a top nordic policy priority . access to valuable data . strong civil society organizations . strong conditions for collaboration . innovative science environments . strong industries . a competitive nordic region . demanding consumers provide a strong platform for user driven innovations this initiative is a clear example of the attempt to build an innovation on a supportive policy environment in order to create social and economic value through health not only locally, but globally. another move toward policy innovations for health based on open innovation approaches is the ever increasing number of platforms, coalitions, alliances, and networks built around health issues. a good example is the european platform on diet, physical activity and health initiated in by the dg sanco of the european commission, which allows the commission to work with a wide range of players across the public, private, and nongovernmental sectors [ ] . the stated intent is to create a platform for concrete actions designed to contain or reverse current trends, platform members must commit to action. as underlined in the white paper on strategy for europe on nutrition, overweight and obesity related health issues, the commission considers that the development of effective partnerships must be the cornerstone of europe's response to tackling nutrition, overweight and obesity, and their related health problems. in such platforms the members agree to monitor and evaluate the performance of commitments in a transparent, participative and accountable way; the eu platform, for example, works to a founding member's statement, has a monitoring framework and produces progress reports. the visibility and legitimacy conferred through such alliances is gaining increasing importance as a policy mechanism as are a myriad of public-private partnerships. actors and issues gain prominence through media presentation and public debate as the health society is also a media-driven society. these platforms constitute a new political space for health and network governance, particularly for very controversial issues. the european commission, for example, uses a multistakeholder platform to address alcohol issues through an "alcohol and health forum," bringing together civil society and businesses pledging to take action to reduce alcohol-related harm in europe [ ] . innovation and knowledge are interdependent. innovation can be defined as the process through which social and economic value is created through knowledge, an issue discussed in more detailed in the chapter by sakellarides. this is done by different forms of knowledge creation, diffusion, transformation, and application. both health and innovation are increasingly dependent on the inclusion of the user and challenged by the democratization of knowledge production. the sociology of innovation describes the innovation paradox, which postulates that in the knowledge society the role of the producer and the role of the consumer move ever closer together -health as well as innovation therefore need to be considered as coproduced goods [ ] . in the area of technological innovation this is often described with terms like open source, open content, lead user, open innovation, collective invention, user innovation, and creative commons [ ] . in health policy this participatory element has been neglected. on the one hand it is particularly difficult for the health care system to accept participation, because it has been defined by a very strong hierarchy between the professional physician, other health professionals, and the patient. yet the management of chronic disease and the adherence to prevention regimes can only be achieved with full participation of the individual concerned. the overlap of unmet medical needs and unmet social needs can only be addressed jointly between patients, providers, and the social support system -patient input is a prerequisite to developing the kind of integrated disease-management models that most health systems still do not provide because they are out of step with the epidemiological and social development. the unmet medical and social need has led to the creation of a wide range of highly active patient organizations and self-help groups who act as the experts on "their" disease. the same applies to prevention and health promotion -the active participation of the individual, social groups, and communities is needed to engage in successful initiatives [ ] . sakellarides in his chapter highlights to interdependence of the knowledge society with innovation in the health society. patients want information, participation, and choices -this is the result of the "european patient of the future" survey from [ ] . consumers want simplicity, convenience, speed, and a good price [ ] . increasingly the two expectations meet as health systems become increasingly market driven and as patients want more say and have higher expectations. new products and technologies can only develop their full potential if they meet processes and structures that allow them to do so. this implies new forms of information, communication, and integration processes. the conference board of canada in its recent analysis [ ] defines three dimensions of high performing health systems: people and culture, technologies, and structure and processes. this is also reflected in the more recent literature on innovation which speaks of a paradigm shift toward a "fluid identity of innovation" [ ] . this means the "old" debates as to what constitutes a radical innovation and an incremental innovation is considered less and less relevant. this is often much more obvious in other, less regulated areas than the health sector. a good example from information technology is the telephone: at what point in the long process from graham bell's machine to the tiny multifunctional mobile instruments we use today do we speak of radical or incremental innovation? when it turned wireless? when it could take photographs? when it became the iphone? whatever it will be in future? similar questions arise in relation to medicines and medical technology which with the rise of chronic disease fulfill more than their primary medical function -they cannot cure any more so they will seek to reduce pain and the progress of disease, lengthen life, improve mobility, ensure independence, be easy to use, etc. the innovation process around medicines for hiv/aids is a typical case in point -every small improvement in the lives of aids patients counts and it continues to be driven not only by medical innovation but a very strong demand from influential user and advocacy groups. probably one of the most important process innovations that needs to be achieved lies in the transparency and accountability of health policy and health systems. hernandez-aguado in his chapter indicates how new types of monitoring could provide transparency and accountability for the impact that other sectors have on health. sakellarides and his coauthors highlight the significance of patient-driven and patient-owned health information, also including the determinants of health. it is indeed worrying that in modern democracies, citizens -once they become patients -do not have access to data on the performance of the system that they enter or even to their own health data. this knowledge-based value creation willas sakellarides states -probably be the most relevant health policy innovation in the next decade. health consumer powerhouse regularly publishes a ranking which indicates in which countries consumers and patients have the most rights and the most opportunities for participation [ ] . a recent german survey showed that most citizens would like to see a ranking of physicians and would like to see their medical bills. [ ] . if health is a coproduced good, then all those that participate in its production have a right to transparency of all elements of the process. the issue of transparency also arises around propriety regulations. in the information technology field, there has been a move toward open access, open source, and open standards, and with the expansion of the internet it has led to new forms of information access and sharing -the exciting mix of social and technological innovation, as reflected in platforms such as myspace and second life. these demand-push innovations have in turn led to highly profitable companies. due to the structure of the proprietary industry and government regulations, much of this innovation process remains closed. it is regularly challenged, in particular, by nongovernmental organization in relation to global health issues innovations -and more recently by the establishment of government assessment agencies. this conflict is not the subject of this book -yet it is worth referring to an interesting experiment at the world economic forum in , which discussed how the break down of proprietary rights in the entertainment industry could be a signal for the pharmaceutical industry to reconsider its approaches with a new and proactive demand-push approach. in some cases this has succeeded at the global level where new forms of pricing, patent policies, and financing of pharmaceutical innovation for diseases of the developing world have been developed, and after much conflict a new cooperation between advocacy groups, the industry, governments, and modern philanthropy has emerged. for this book the key issue is that health is no longer a given; it is produced, maintained, and enhanced. the results of health research are rapidly transported through the media -a new cure, a new method of prevention, a new confirmation of old behaviors, all have high currency in the health society. what is considered healthy today might not be so tomorrow -new risks continuously emerge [ ] . as a consequence heath literacy plays a critical role [ ] . risks are frequently not visible or seem intangible and they need to be well communicated, and above all understood and translated into action. as more and new health information becomes available this can become a difficult challenge for ordinary citizens in particular if they are not well educated or even functionally illiterate, as about % of all citizens in the oecd countries are. the expansion of health choices and the complexity of health systems demand an ever higher degree of sophistication and participation, and as a consequence there is a growing offer and demand not only for health information but for advice and knowledge brokering. to be a passive and compliant patient who follows the physician's instructions is no longer sufficient -particularly when related to preventative issues. indeed the emerging model is one of active and critical consumers, an ideal that only few members of the population can aspire to achieve. already today -despite the universal access to health care -health inequalities abound even in the richest countries, and there is a clear danger that they will widen even further as the health society expands. the very presence of health in all areas of everyday life can also lead to a variety of reactions -either to attempts to reach an unrealistic body image or to conscious risk taking in opposition to an overpowering set of health messages and expectations. while the health society offers many opportunities of empowerment, it can also be prescriptive and exert social control through health [ ] . within a health society there has to be constant democratic dialog about the societal value we attach to health, a debate that has barely begun. providing access to information on health and new health products and services including e-health is only a small part of the issues at stake as sakellarides points out in his chapter. there is in general a big democratic deficit in relation to health and health policy, which needs to be addressed with urgency: the reorientation toward participation and user involvement will be one of the most important governance shifts in health. what will innovation in health policy imply in the st century? if innovation means a reorganization of how we approach health in st century societies, i propose that the following five dynamic processes will be critical. our societies will need to • develop a new understanding of health as an investment and productive force in society • develop separate governance mechanisms for health and for health care, with a strong focus on accountability for health gain • augment the concern for ethics and values with respect to health through a broad dialogue with citizens in order to increase democratic legitimacy and ensure solidarity • move beyond a narrow understanding of health outcomes in terms of only physical health measures to those that aim to include or even prioritize broader measures of wellbeing • engage in network governance, partnership and multi-stakeholder approaches in rder to achieve health goals. the big st century health challenges call for more courageous and democratic policy approaches than applied so far. while our societies have now learned to recognize the urgency of the environmental challenge in terms of long-term sustainability, we are only just beginning to grasp the consequences that our way of life has in terms of health sustainability. an example of developing such a change in mindset are the health in all policy principles developed in the south australian government in through a health in all polices process [ ]. a "health in all policies" approach reflects health as a shared goal of all of government. in particular, it . recognizes the value of health for the well-being of all citizens and for the overall social and economic development of south australia. health is a human right, a vital resource for everyday life and a key factor of sustainability. . recognizes that health is an outcome of a wide range of factors -such as changes to the natural and built environments or to social and work environments -many of which lie outside the activities of the health sector and require a shared responsibility and an integrated and sustained policy response across government. . acknowledges that all government policies can have positive or negative impacts on the determinants of health and such impacts are reflected both in the health status of the south australian population today and in the health prospects of future generations. . recognizes that the impacts of health determinants are not equally distributed among population groups in south australia and aims at closing the health gap, in particular for the aboriginal peoples. . recognizes that health is central to achieving the objectives of the south australian strategic plan -it requires both the identification of potential health impacts and the recognition that good health can contribute to achieving south australia strategic plan targets. . acknowledges that efforts to improve the health of all south australians will require sustainable mechanisms that support government agencies working collaboratively to develop integrated solutions to current and future policy challenges. . acknowledges that many of the most pressing health problems of population health require long-term policy and budgetary commitment as well as innovative budgetary approaches. . recognizes that indicators of success will be equally long term and that regular monitoring and intermediate measures of progress will need to be established and reported back to south australian citizens. . recognizes the need to regularly consult with citizens to link policy changes with wider social and cultural changes around health and wellbeing. . recognizes the potential of partnerships for policy implementation between government at all levels, science and academia, business, professional organizations, and nongovernmental organisations to bring about sustained change. an additional complexity is due to the fact that health in the st century is inherently global and many determinants of health are no longer in the control of nation states. global and regional agreements of an economic and political nature can seriously endanger health -as experienced in rising alcohol rates in finland and sweden when they joined the european union -or they can move the health agenda forward through transnational and global health agreements. the last years have seen the acceptance by the who member states of both the international health regulations and the framework convention on tobacco control. but other less binding approaches, such as the forceful move on a global strategy to combat chronic diseases, the policy by the european union to consider the health impacts of all policies of the eu, the discussions on health at the davos world economic forum, the new priority assigned to health in the oecd, and the product shift of many global companies, all illustrate the global driving force that health has become. concerns arise around the global pharmaceutical market as much as over the global spread of sugary soft drinks, the global movement of health professionals as much as over the rapid global spread of viruses [ ] . while the policy innovations for health required at the global level are not subject of this book, the authors are aware that this global nature of health is in itself one of the most significant driving forces of the reorganization of health in the st century. magazine daily summary. oecd forum innovation, growth and equity, paris france - exploring technological innovations in health systems. conference board of canada oecd health and innovation survey the consequences of modernity liquid life health and modernity leading for innovation: & organizing for results social determinants of health health and consumer protection directorate ( ) the contribution of health to the economy of the european union tackling obesity -future choices project report sweden's new health policy. stockholm . public health agency of canada: determinants of health world health organization (who) ( ) constitution settings' based health promotion: a review territorial innovation models: a critical survey canadian index of wellbeing the nordic region as a global health lab theorie der wirtschaftlichen entwicklungen ( . auflage, ursprünglich ) wandel im gesundheitsmarkt: strategische ausrichtung der pharma-und biotechindustrie auf künftige marktbedingungen und träventive therapien. dissertation, eth zürich ) lissabon strategie. ec.europa.eu/ growthandjobs/index de die gesundheitsgesellschaft securing good health for the whole population. hm treasury. www.hm-treasury.gov.uk/consultations and legislation/wanless/consult wanless final.cfm open innovation health targets in europe adelaide revisited: from healthy public policy to health in all policies health strategy white paper fighting cardio-vascular diseases by prevention and early diagnosis eu platform on action on diet, physical activity and health. ec.europa.eu/health/ph determinants/life style/nutrition/platform/platform en.htm . hippel e. von ( ) democratizing innovation the european patient of the future. picker institute europe sustainable innovation as a corporate strategy consumer power house health consumer powerhouse: euro health consumer index ( ) www.healthpowerhouse.com/media/rapport ehci die ambulante versorgung aus sicht von bevölkerung undÄrzteschaft health literacy. towards an active health citizenhip risk and socio cultural theory, new directions and perspectives. cambridge special theme: health and foreign policy some parts of this chapter are based on a working paper for the academic advisory group, which provided the guidance for the work on this publication. it was published as an editorial. ( key: cord- - biitdl authors: stonik, v. a.; tolstikov, g. a. title: natural products: designing russian medications date: - - journal: her russ acad sci doi: . /s sha: doc_id: cord_uid: biitdl the study of natural products (low-molecular bioregulators) is an important research area that lies on the boundary of biology and chemistry. it involves searching, isolating, and identifying the structure and studying the biological functions of such substances, as well as investigating their chemical conversions, especially those that lead to highly active products. these research efforts play an important part in deepening biological and chemical knowledge and build the scientific groundwork for designing new drugs and biologically active food additives. some results of the study of natural compounds were discussed in a paper read at a session of the ras presidium and are published below. issn - , herald of the russian academy of sciences, , vol. , no. , pp. - . © pleiades publishing, ltd., original russian text © v.a. stonik, g.a. tolstikov, , published in vestnik rossiiskoi akademii nauk, secondary metabolites are biological molecules without general distribution. in contrast to primary metabolites, they can only be found in certain taxa or even in one biological species. these substances are formed from predecessors that take part in primary metabolism, such as amino acids, monosaccharides, and others, and they mostly are the final products of their biochemical conversions. secondary metabolites are known to be physiologically active, and some of them (morphine, quinine, cholesterol, and others) were among the first organic compounds to be isolated almost years ago. it took the efforts of several generations of scientists to determine the chemical structures of such substances. secondary metabolites are diverse in their chemical structure and include steroids and terpenoids, alkaloids and polyketides, phenol metabolites and some carbohydrates, and various lipids and peptides. by biological functions, they are generally classified as vitamins, hormones, antibiotics, toxins, pheromones, and many other groups. in the russian and international literature, such compounds are often called natural products, although, of course, other types of biomolecules, including proteins and nucleic acids, are equally natural. nevertheless, here we will use the term natural products solely with respect to secondary metabolites: predominantly exogenous compounds that enter a human body together with food and drugs. however, natural products include both endo-and exometabolites, that is, substances with certain biological functions in producer organisms, for example, hormones, phytohormones, alexins, and substances that are excreted by these organisms into the environment and that are of great ecological importance, among them toxins, antibiotics, and various signal compounds. the main biological sources of natural products are supreme terrestrial plants, soil microorganisms, and various marine organisms. the total number of known natural products does not, probably, exceed - , but many experts believe that it is considerably smaller [ ] . for reference, by now, chemists have synthesized about million organic compounds. research into natural products is associated with the names of a whole series of prominent scientists. about outstanding researchers became nobel prizewinners for the discovery, determination of the chemical structure, synthesis, and study of the biosynthetic routes, biological role, and mechanisms of vitamins, hormones, antibiotics, prostaglandins, sterols, and other natural products. note that slightly more than half of the prizes were awarded in chemistry and the rest, in medicine or physiology. this testifies to the fact that the study of natural products is an integrated area at the junction of chemistry and biology. having originated as a section of organic chemistry, the study of natural products played a significant role in the development of this science. it brought about the discoveries of new chemical reactions, including various rearrangements, and substantially spurred the perfection of the art of organic synthesis. today, the most sophisticated chemical problems, including complete directed asymmetric synthesis, are posed by natural product researchers, while the chemical efforts themselves are often performed by teams consisting of dozens of expert synthetic chemists. this division of natural science is closely related to extending biological knowledge, too. of great importance were the determination of molecular mechanisms responsible for the biological action of many highly active compounds and the creation of modern concepts for designing novel and more effective drugs for various therapies; a broader understanding of the molecular grounds of physiological processes, including those of nerve conduction, vision, and olfaction; and many other discoveries that were made using low-molecular natural compounds. examples are the discovery of basic routes in the biosynthesis of terpenoids, steroids, vitamins, and hormones; the identification of pheromones and allomones; and the determination of the mechanisms of chemical intra-and interspecies signaling. researchers who deal with natural products are very enthusiastic users of state-of-the-art achievements in chromatography, both nmr and mass spectroscopy, analytical instrument making, and various aspects of mathematical simulation, including computer docking for predicting physiological activity (so-called biotesting in silico ). it is no wonder that work on isolating and determining the structure of new natural compounds, which only recently involved many years of efforts, can now in many cases be accomplished within several weeks, using just a few milligrams of the target substance. it should be noted, however, that today, too, nat-ural product researchers quite often face structural tasks that cannot be solved in a short time, even using very powerful separating and spectral equipment. the applied importance of efforts in this area of research is primarily determined by their biomedical orientation. first, approximately % of modern medicinal preparations have been designed on the basis of the study of natural products [ ] . for a drug's biologically active substance (bas), either the natural product itself or its synthetic derivative or analog may be used. second, natural products that have one specific action or another on biological systems are frequently used as biochemical reagents for studying the molecular action mechanisms of new bass. natural products are also important as food components. the presence of vitamins, antioxidants, and other useful natural compounds makes nutrition adequate, and so-called biologically active food additives stonik, tolstikov (bafas) are being used to try to compensate for a lack of them. they are used increasingly more in advanced countries. in the united states, for example, there are registered bafas, and in russia, , including a host of foreign preparations. fraudulent advertising often presents bafas as a "cure-all," while they, as a rule, do not cure any serious diseases but generally are preventives and analeptics. in the united states, the portion of people who take bafas is more than %. we may expect that the use of bioadditives in russia will grow too, the more so because in recent years progressively more valuable qualities have been discovered in natural foodstuffs. three recent examples could be the clinical confirmation of antitumor properties of epigallocatechin- -gallate from green tea; the explanation of the so-called "french paradox" (a relatively rare occurrence of cardiovascular diseases in french southerners who regularly drink red wine and eat fatty food) by the presence of resveratrol in red wine; and the discovery of red-pepper capsaicin's ability to destroy malignant cells. it is impracticable to provide an exhaustive analysis of recent papers in a vast area of research like natural compounds. therefore, we will confine ourselves to some foreign and russian examples that to some extent characterize the trends in this work. the russian findings come mainly from two academic institutes: the pacific institute of bioorganic chemistry, ras far east division, vladivostok, and the vorozhtsov institute of organic chemistry, ras siberian branch, novosibirsk, where natural product research is represented by biomolecular and chemical areas. as regards other countries, we will discuss longterm investigations aimed at designing new-generation antitumor drugs based on marine natural products. thus, some marine invertebrates were found to contain minor but superactive secondary metabolites that have an extremely high toxicity for tumor cells: they exceed the majority of present-day antitumor drugs by hundreds and thousands of times. for example, spongistatin ( fig. a ) from tropical marine sponges is the most active of all natural and synthetic compounds ever found in antitumor studies at the national cancer institute (united states). this substance was first discovered in the sponge owing to the biological activity of related extracts, but it took a long time to isolate it in quantities needed for structural investigation. only after gathering and processing three tons of the sponge was it possible to obtain . mg of spongistatin. then, a different type of sponge was used as a source material, and kg of it, collected near the maldives, yielded mg of spongistatin. following the validation of its structure, researchers began studying the physiological behavior of this macrolide. the inhibiting dose causing the death of % of tumor cells was - m (for rectal cancer) and - m (for breast cancer). in experiments on animals with lethal malignant tumors, the administration of spongistatin in a µ g/kg dose resulted in % survival. about natural products whose activity is in many cases comparable with spongistatin's are currently at different stages of clinical trials as antitumor drug candidates [ ] (see table) . researchers from the pacific institute of bioorganic chemistry have isolated more than new natural products and determined their chemical structure, including, in many cases, absolute stereochemistry. moreover, they discovered (sometimes, jointly with immunomodulators; hepatoprotectors; and other valuable natural products from marine and terrestrial biological sources. they also studied molecular action mechanisms, conducted full syntheses, and thoroughly examined the physiological activity of a whole series of the most interesting substances. thus, the first representative of bipolar sphingolipid-like metabolites, rhizochalin ( fig. b) from tropical sponges, showed antifungal activity, even against drug-resistant fungi that are agents of mycoses in aids patients. alkaloids from polycarpine (fig. c) and varacin (fig. d ) sea squirts demonstrated high antitumor activities. in terms of tumor cell toxicity, the latter surpasses the wellknown doxorubicine and has a higher activity in an acidic medium, which is associated with some selectivity for tumors versus normal tissues. indeed, it is generally known that many tumors acidify themselves due to increased glycolysis. glycosides from commercial holothurians, for example, cucumarioside (fig. e ), appeared to be strong enhancers of cellular immunity, and acidified steroids from starfish, including asterosaponin ê (fig. f) , stimulators for neural tissue process (neurite) growth. the results of basic research carried out at the pacific institute of bioorganic chemistry have become the groundwork for applied developments, in particular, new drugs, bioactive food additives, diagnosticums, veterinary medications, and biochemical preparations. thus, long-term observation of quinonoid pigments from urchins led to new medicinal preparations: histochromium for cardiology and histochromium for ophthalmology. both, especially the latter, have been widely used in russian practical medicine in the last five years [ ] . the study of the extracts of terrestrial plants that grow in the russian far east resulted, following pharmacological and clinical trials, in a new hepatoprotective drug, maxar, which has recently been registered and released in russia. today, supported by a government contract, the maxar in-process test is coming to an end, and the first pilot batch is being prepared for production. the final stage of the study of unique proteinase enzymes from seafood processing waste was the creation of a new wound healing remedy, kk collage-nase. under the ras presidium's programs "basic sciences for medicine" and "molecular and cellular biology" and a government contract, the design of a new immunostimulant, cumaside; a new drug formulation "synthetic histochromium for cardiology"; and a number of other promising preparations is underway [ ] . among biologically active food additives designed by far eastern scientists, the best known are the herbamarine alcohol-free balsams (four balsams of different effects) and a polysaccharide preparation zosterin from seaweeds [ ] . basic research at the novosibirsk institute of organic chemistry is targeted toward developing physiologically active compounds through synthetic conversions of natural products. they carry on the glorious traditions of prominent national phytochemists, whose developments underlay the pharmaceutical industry of the soviet union. note that even now, this path of designing new drugs remains central in the world. for starting compounds (synthons), siberian researchers use accessible secondary metabolites from terrestrial plants that grow in russia. among them are well-known compounds like betulin from birch-tree bark ( % content by dry weight); glycyrrhizic acid, produced from licorices; and oleanolic and ursolic acids from pressed cranberry, buckthorn, and other berries. lambertian and levopimaric acids and resveratrol may be extracted from the needles, turpentine, and bark of some conifers; abietic acid, from colophony; and available and cheap monoterpenoids ( αand β -pinenes, limonene, and many others), from plant essential oils. licorices, especially, their roots (licorice roots), are widely known for their healing properties. they have been used for almost years. they have adaptogenic, antiulcer, and tonic properties and contain glycyrrhizic acid as the main physiologically active component. in the formula given in fig. a , arrows designate the moieties (sites) that have undergone chemical conversions in the studies of synthetic chemists from novosibirsk. thus, by attaching two remains of amino sugars to the carbohydrate chain, they managed to synthesize substances that inhibit the virus of atypical pneumonia (sars), an epidemic of which, according to experts' prediction, may lead to a loss of millions of human lives. other conversions in the carbohydrate chain of glycyrrhizic acid yielded substances with antiviral activity towards dangerous viruses like the human immunodeficiency virus, the ebola virus, and the marburg virus. polycyclic aglycone modification allowed one to synthesize chemical compounds capable of controlling sodium-potassium metabolism [ ] . one interesting property of glycyrrhizic acid is its capability to form inclusion complexes with various low-molecular pharmaceutical substances (pharmacons). such clathrates of general formula (fig. b) synthesized by siberian scientists possess wonderful properties. being, in essence, nanocapsules that carry physiologically active components, they protect their stonik, tolstikov content from fast metabolic deactivation and ensure its delivery to receptors and tissues. as a result, it has become possible to decrease the doses of known drugs several times, reduce their adverse reaction, and enhance their medicinal effect. we believe that this nanotechnological area shows much promise [ ] . betulin gave rise to highly active derivatives of betulinic acid: betulavir (fig. c) , a new promising candidate for a drug for human immunodeficiency, and βalaninamide of betulinic acid (fig. d) . betulavir effectively inhibits the human immunodeficiency virus (the inhibiting concentration is . nm), being one of the most active inhibitors among all antiviral compounds studied so far. the latter compound is capable of inhibiting the growth of primitive tumor nodes and reducing considerably the number of metastatic nodes in the lungs and liver of experimental animals with induced malignant tumors. at the same time, it shows organprotective properties against the background of experimental polychemotherapy. these properties enabled the researchers to offer it as a toxic effect corrector for cytostatics [ ] . from lambertian acid (fig. f) , point transformations helped synthesize compounds e and g , of which the former has nootropic properties. as is commonly known, nootropic preparations represent a class of physiologically active compounds that improve higher brain functions, including mental efficiency, and have none of the side effects inherent in psycho- stimulants [ ] . compound g showed a high antileukemic activity [ ] . chemists from the novosibirsk institute of organic chemistry have synthesized many hundreds of new physiologically active compounds and discovered unusual rearrangements and other conversions of organic compounds. these investigations have significantly enriched the organic chemistry of natural products and set up the scientific groundwork for designing new effective drugs. prospects and problems one recent trend in this field has been the emergence of a new research area, metabolomics. this is a system study of low-molecular metabolites, sui generis chemical "fingerprints," which specific intracellular processes leave in the organism [ ] . the subject of investigation here is a metabolome, a set of all low-molecular metabolites of an organism. in january , american scientists who were involved in a homo sapiens metabolome project reported the identification of endometabolites, medicinal drugs, and compounds of food origin in a human body [ ] . metabolomics was subdivided into lipidomics (science about all lipids in an organism), glycomics (science about carbohydrates), and other branches. metabolome research became possible only following revolutionary progress in separation and identification methods in the late th-early st centuries. it should be emphasized that this research is still in the initial phase of development and is generally confined to the study of the human metabolome. the metabolomes of other inhabitants of the globe remain insufficiently explored. metabolomics is closely related to so-called metabonomics, a science about dynamic changes of metabolomes in response to pathophysiological stimuli and genetic transformations. metabonomics is also based on the application of modern achievements in nmr, mass spectroscopy, and high-performance chromatography. this new research area opens up broad vistas for diagnostics of various, including genetic, diseases. obviously, efforts related to seeking and identifying natural products in various biological objects and studying their seasonal variation and concentration fluctuation depending on other factors are the crucial elements of metabolome projects. another trend is also connected with increasing the effectiveness of natural product research techniques. it consists in a growing share of research into minor secondary metabolites, the content of which in extracts is less than . %. some of them possess physiological activity as high as the above-mentioned marine supercytotoxins: spongistatin, dolastatin, and others. the socalled "active metabolites"-intermediate products in the biosynthesis of various natural products-do not essentially accumulate in any noticeable amounts in producer organisms and are minor metabolites, too. identifying minor metabolites is an important path to understanding the mechanisms and routes of biosynthetic conversions and the study of biochemical combinatorics in secondary metabolism. the latter is closely related to an evolutionary search for new chemical means of adaptation in living systems. the discovery of an extremely high physiological activity in a whole series of minor metabolites of marine and terrestrial origin is progressively increasing the demand for complete asymmetric organic synthesis of natural products. such synthesis not only improves the methodology of organic chemistry and is very attractive intellectually, but in many cases is the only method to make medically promising natural products available for pharmacological and clinical trials. as a rule, other simple natural compounds or their products, which resulted from chemical transformations and retained their asymmetry, may be used as synthons. unfortunately, russian efforts in complete asymmetric synthesis of natural products are very limited. to intensify them, we need to develop special interdepartmental programs, support the existing centers of research in organic synthesis, and find resources for the acquisition of up-to-date, including chiral, synthons and reagents. the close relationship between comprehensive research into natural products and medicine entails a host of problems in putting basic research results into practice. this is especially true about designing new medicinal preparations. indeed, in today's russian pharmaceutical market, domestic drugs account for less than %, with just % of cardiovascular, % of antitumor, and % of psychotropic medications (p.v. lopatin's data, ). the situation may be corrected only by increasing attention to the promotion of research into the bioorganic chemistry of natural products and other biomolecules, molecular biology, and organic synthesis; ensuring government support; showing interest in designing new preparations by the pharmaceutical industry; and using the synergies of the russian academy of sciences and the russian academy of medical sciences. in recent years, a great number of extremely active substances have been discovered. some of them are now in the phase of preclinical or even clinical trials as bas candidates. in some modern preparations, biologically active substances are so strong that their kilogram (or, sometimes, gram) quantity would be sufficient to meet russia's demand in them. their production scale would be called micro-rather than small-tonnage chemistry. as a rule, the manufacture of such bass does not need large production areas but may be done only by the most qualified personnel. bass may be produced using, for example, the pilot plants of ras or rams institutes. generally, the establishment and expansion of the existing pilot plants is a necessary step in innovation activity, which should enjoy all-round support. finally, the practical application of the findings stemming from biological and chemical research into natural products largely depends on biotesting. it would be reasonable to increase the number of laboratories dealing with research into the physiological action of particular compounds on viruses, various cells, and tissues, improve their funding, and coordinate their efforts. in our opinion, russia should have more up-todate vivaria with laboratory animals, centers for preclinical studies, and medical institutions authorized to conduct therapeutic drug monitoring. finally, three years ago we received an empty building without any process equipment. through our own efforts, we have been expanding production and activating sites one after another. in so doing, we try to comply with the gnp rules. we have prepared a sterile area and staging areas for air, vacuum, and extraction using organic solvents. recently, we produced an active substance for the new drug maxar. we have received a grant to support the development of such technologies, and we plan to activate four more sites in the near future. academician s.m. aldoshin: i have two questions. one is connected with the practical application of the discussed natural products in medicine. it has been a long time since chemical medicinal compounds ceased to be synthesized without preliminary computer processing, which identifies the most promising ones. is there any ideology in this respect? stonik: of course, there is. the ideology consists in selecting biological objects for work after so-called screening. for example, when collecting biological material from onboard a research ship, as in a recent case in vietnamese waters, tests were conducted immediately on board. selected objects are recollected, and then, fractions, substances, and so on, are extracted through biotesting. aldoshin: so, you do screening. do you first extract whatever is extractable and then look at test results to identify what may be useful? stonik: yes. in addition, we do so-called virtual screening. using supercomputers and computer docking, we select from the collection suitable substances based on their action on molecular targets. then, having predicted their physiological activity using mathematical computer-based approaches, we try to check everything. quite often, when this is impossible due to the fact that such biotests have never been conducted in russia, we have to contact our colleagues in other countries. aldoshin: any correlation with the software used by academician n.s. zefirov? stonik: yes, in effect, we are using the same computer docking and the same mathematical processing for activity prediction. of course, we do not have the massive opportunities of synthetic chemists who have a considerably larger range of substances available. however, we use these methods, too, although biological screening prevails. academician d.v. rundkvist: what you have discussed is clear even to a researcher in another area, and the importance of these studies is obvious. however, there are interfacing problems; your report has a very general title, natural compounds. we understand that, for example, quartz and potassium are classified as natural products. your scientific presentation, which is generally basic, shows promise for applied research as well. therefore, i will allow myself to ask the following question. today, of paramount importance are new extraction methods using the biotechnology of elementary particles that are at the nanolevel rather than in lattices. does your institute pursue such investigations? stonik: our institute did some small-scale work of such a kind jointly with geologists from the amur integrated research institute, ras far east division, who were involved in extracting gold using microbial and other methods. we have also started to work in other nanotechnological areas: molecular encapsulation, clathration, and others, which allows one to reduce the amount of substances needed for medical or other purposes. however, these are just "incidental" efforts. rundkvist: you mentioned enzymes and various diseases that may be healed using methods developed by you. do you have adequate test facilities to be able to test human blood enzymes in full? stonik: we do not do clinical tests; yet, we identify some enzymes and use them for screening. as regards test facilities, we have established a multiaccess center, one of the largest in the far east. it enables one, for example, to determine a structure if the compound in question is available in or mg. rundkvist: today, there are a few centers in the world to deal with diseases caused by so-called disproportional enzymes. the central tool here is analytics, because it is almost impracticable to cure a disease without first analyzing its nature. what is the degree of adequacy of your analytical methods? stonik: we do our best to expand our analytical facilities, and our chromatographic facilities are not bad, but one cannot square the circle. academician n.a. shilo: since marine organisms differ from terrestrial ones, i would like to know if they differ in nuclides or some other parameters. stonik: of course, there are significant genetic distinctions between marine and terrestrial organisms, which broke apart in the course of evolution long ago. most ancient marine invertebrates emerged more than million years ago. their distinctions are determined by the genome and manifested, among other things, in natural low-molecular compounds. academician v.a. chereshnev: in your investigations, you demonstrated an extremely strong antitumor action of new drugs. what kind of tumors did you study: epithelial, tissue, or leucosis? stonik: the initial search is performed on leukoses; these are the most popular models; and then we normally switch to melanomas. the substances i mentioned were studied on a panel of about diverse tumor cells. the highest activity was shown for melanomas. chereshnev: immune deficiency has a rather broad definition. which immune deficiencies are meant: combined, cellular, or humoral? stonik: cumaside mainly affects cellular immunity, although humoral immunity is weakly stimulated too. chereshnev: you activate the immunity system through repeated administration of polysaccharides or protein molecules, when antibodies, lymphocytes, and neutralizing drugs are accumulated. do you have to administer a larger dose each subsequent time, or have you found a way to evade the immune response? stonik: these substances stimulate cellular immunity in very low concentrations, and the stimulation continues for about three to four weeks. as a rule, there is no need to repeat stimulation, but if you have to repeat it, do it after some break. academician yu.v. natochin: how do you solve the problem of studying in vitro, on tissue, and on a whole organism? who is the qualified assessor of your research results? stonik: naturally, the study of any physiologically active substance begins with in vitro experiments. then we switch to in vivo tests and use, for example, magnetic resonance imaging. we have one of only a few magnetic resonance tomographs for laboratory animals in russia. when we use a model disease (for example, stroke) and substances selected in research at a cellular level, it enables us to assess the result already on laboratory animals. of course, there are a great number of substances that show wonderful activity in vitro but fail to exhibit it in vivo. nevertheless, this is the path taken by all researchers, because there is not yet an alternative, but to experiment in vivo on animals starting with extracts or unpurified fractions is very expensive. academician yu.s. osipov: what is the situation with the use of, as you put it, chemical fingerprints for diagnosing various diseases in other countries? what particular diseases are meant? stonik: this is just an idea at the moment. i do not know any particular cases. perhaps they are known, but not to me. how did experienced country doctors make a diagnosis early in the th century? by skin color in a particular area or by their patient's smell, and quite often the diagnosis was correct. if such an approach is supplemented with supermodern chromatographic and other methods, the diagnostics of many diseases will clearly be successful. osipov: you mentioned biotesting centers. are such centers available in major modern russian pharmaceutical companies? are there any arrangements to use their equipment for tackling your problems? stonik: unfortunately, our experience has been negative. neither in russia, nor in other countries, are there major pharmaceutical companies prepared to invest in the issues we are interested in. they normally accept either ready or half-ready preparations, and only later do they become their business. abroad, creating a new antitumor drug costs $ million. of course, in russia, we do not have such money, and we cannot hope that private companies, including foreign ones, which have bought nearly all russian pharmaceutical enterprises, would help us in our hard work either. in this respect, the situation is far from being optimistic. survey of chemistry of natural compounds ed natural products as sources of new drugs over the last years drugs from the deep: marine natural products as drug candidates biotechnological studies in the far-eastern region of russia on the way to low-dose medicines lupane series terpenoids as biologically active agents perspective for medicine. part : semisynthetic lupane derivatives nootropic activity of derivatives of lambertian acid gram-scale synthesis of pinusolide and evaluation of its antileukemic potential growing pains for metabolomics the human metabolome database a question from the audience: you mentioned your institute's pilot facility. how is it developing?stonik: our pilot facility is developing with difficulty. its history is very interesting. it was initiated by m.s. gorbachev, who visited our institute about years ago, and then the construction was suspended. key: cord- -l jzpxi authors: topper, benjamin; lagadec, patrick title: fractal crises – a new path for crisis theory and management date: - - journal: nan doi: . / - . sha: doc_id: cord_uid: l jzpxi this paper is a modest contribution to the vast exploration to be embarked upon as our maps appear increasingly outdated. we will first explore some outmoded ‘taken for granted’ assumptions and visions: this section aims to clarify why the crisis management world has profoundly changed and how the current understanding of crises and theoretical frameworks is becoming increasingly less adequate. then, we will try to meet the second challenge of this special issue, by suggesting innovative approaches that will contribute to elaborate the building blocks of a theory of crisis management. we will propose a new theoretical framework, through the use of a fractal approach, following the footsteps of benoit mandelbrot, in order to rethink and capture the essence of the new theatre of operations that must be dealt with. throughout, we will show how this original framework could be put into practice and what its limitations and perspectives are. n ormality is our natural nest, stability our beloved home and certainty our paramount aspiration. decision makers ask for action, but properly mapped. business people ask for risk, but properly controlled. wild weather is the friend of no one. academics -sons of descartes, so 'delighted with the mathematics, on account of the certitude and evidence of their reasonings' (descartes, ) -are eager to understand the world and its laws, but within proper limits. as alvin weinberg put it:'science deals with regularity; art deals with singularity' (weinberg, ) . alas, from time to time, some big storm, disaster or 'situation' rears its ugly head to disturb, for a moment, the so-called 'normal' world. a dominant tendency is just to ignore such improper outbreaks, and to concentrate on the 'normal' game plans.yet, some bold thinkers -philosophers, doctors, strategists, lawyers, mathematicians and economist -have always been captivated by such strange quirks of 'nature' and history. ever since the ancient greeks, 'crisis' has received special attention: how to envision and deal with such difficult trials sent by the gods or nature? the quest has always been seen as foolish: how to study the exception to the rule, the 'irrational'? and dubious too: those studying such disturbances were incapable of providing a clear definition of their elusive 'object'.and probably blasphemous into the bargain: you do not question the gods nor the laws of nature and science. in a sense, the very idea of a 'theory' of crisis appeared and still appears as a contradiction in terms, both inconsistent and suspect (béjin & morin, ) . however, in addition to isolated thinkers who dared to explore such fields of experience, others succeeded in developing real schools of thought and even 'best practices' for such ordeals. the s and s witnessed the remarkable development of sociological studies devoted to communities confronted with natural disasters (quarantelli & dynes, ) and studies of international crises were prolific (hermann, ; allison, ) . in the late s, and increasingly in the s and s, the field was opened up to take stock of the new kinds of shocks that impact complex technological societies, beyond natural disasters alone. a profusion of severe turbulences were examinedinternational shocks, factory explosions, product tampering, prison protests, urban riots, football stadium tragedies, train or plane hijackings, specific financial crises, etc. case studies multiplied and sustained efforts were made to consolidate theoretical perspectives and models (rosenthal, charles, 't hart, ; lagadec, ) . in parallel, much was done to clarify number of 'best practices' to deal with these events and their ripple effects (fink, ; ten berge, ) . many disciplines were mobilized to open up new lines of thought and to lend their support to the development of knowledge. yet a lingering plea was made to consolidate, beyond mere case studies, some better 'theory' of crisis. then came the turn of the millennium, with a host of new challenges to address. it was patently clear that new kind of crises had to be considered, that a broad new ocean of complexity and 'inconceivability' had yet to be explored:'what we learn about the development and management of past crises may have limited value for improving the management of tomorrow's crises' (rosenthal, boin, & comfort, , vii) . ten years later, such a warning appears more urgent than ever. climate change and environmental issues, increasingly risk-prone vital networks, massive terrorist threats, huge increases in the cost of disasters due to global coupling and just-in-time production methods, global civil unrest, financial and economic meltdowns show that we have to deal, not with something more, but with something else (boin & lagadec, ) . the time of mega shocks (oecd, ) has come. in response, the concept of mega crisis has been put forward and is now trying to get its head around a whole set of questions and theoretical challenges (helsloot, boin, jacobs, & comfort, ) . but scale is certainly not the most difficult factor of rupture. crises appear to have taken on an entirely new dimension: they are no longer isolated accidents capable of threatening large subsystems -the core of our theoretical fabric of crisis theory in use. they have increasingly become opportunistic expressions of global turbulences impacting our social fabrics, while at the same time our bedrocks are losing their firmness of footing by being exposed to violent liquefaction processes. all the various isolated currents of vulnerability seem to be meshing to produce a global volatile, chaotic, incomprehensible theatre of operations. a quarter of a century after the blossoming of crisis studies, the need for a decisive breakthrough appears crucial in the present world, where crisis is no longer the marginal exception but the core engine. hence, tough questions arise. is the paradigm in which our practices (boin & mcconnel, ) and theories are anchored still valid? if not, kouzmin's perspective must be taken on board -'crisis management in crisis' (kouzmin, ) .what can be put forward at the theoretical level to ensure that analytical tools are able to grasp present realities -which are no longer those of last century? in the light of such questions and proposals, how can we develop our action repertoires, and what are the avenues of research that need to be consolidated today? this does not mean that we throw all known practices overboard, but that we must open new windows, to shed new light upon challenges poorly addressed by existing theories. the aim of this contribution is to try to tackle this formidable theoretical and managerial challenge. in the first part, we will revisit our references in the field of crisis -those fixed in recent decades: an overview of the facts, which have effectively slipped the net of our conventional theoretical fields, followed by a critical analysis of the essential roots of our crisis theories. then, in the second part, we will suggest a specific theoretical path, inspired by fractal geometry -which we will show to be well suited to grasping today's volatile realities. finally, we will look at how this original framework can lay the theoretical basis for effective crisis management. clearly, this contribution will not settle all the problems or clarify all the theoretical questions. the aim is only to open new doors, to suggest new approaches, understandings and grammars. it will take many years to build a satisfying theory and to forge new practices for the new world of crises. indeed, our field of experience is witnessing too many upheavals to leave our visions, hypotheses and tools unquestioned, and these same visions, hypotheses and tools have to be reforged if we still want to be in a position to grasp and deal with the realities that are now shaping and overwhelming our history. it is common to reject any idea of novelty, especially in the disaster and crisis area -'nothing new under the sun'. it is traditional to recall the cataclysmic events that have marked history or prehistory (without referring to myths like the deluge) from the extinction of the dinosaurs by a meteorite, the end of the minoan civilization due to a volcanic eruption, the black death ( - ) which decimated europe, the laki eruption ( ) and its contribution to the french revolution, up to the great flu ( ) which killed more human beings than the great war, the crisis, and so on and so forth. not forgetting 'near misses' such as the cuban missile crisis ( ), when the future of mankind was in the balance only to be saved from the brink by the intelligence of a few -or, according to the latest analyses by robert mcnamara (morris, ) -by sheer luck. theories developed in the last decades of the previous century, has commonly been rejected. but, just over years into this century, too many cases have arisen that demand a new vision (lagadec, ) . beyond immediate 'facts' -from katrina to fukushima, from the global financial and economic meltdown to global outbursts of civil unrest -we need to clarify structural factors that change the whole territory of crises, and call for a decisive upgrade of crisis theory. • from large-scale to off-scale: major events are not new, but they have got denser, and appear to affect greater numbers, even entire continents and the entire planet, threatening millions, hundred of millions -because of blackouts, pandemics, economic upheavals and social implosions. multiplication and concomitance of such mega shocks lead to situations where the means are overwhelmed, where everyone or almost, is under the threat. • from complexity to the unreadable: everything can be qualified as complex, but such events as hurricane katrina ( ) have shown how today mega shocks can trigger tremors that are impossible to categorize and map. the case of hurricane irene ( ) striking the east side of the american continent is a warning sign: it is impossible to know in advance the potential multiple-head strikes and disruption dynamics -airports, stock exchange, vital networks, military capacities, etc. -of such mega shocks.the field of the complex event gives way to the totally elusive global situation. • from tightly-coupled to total interdependence: much has been said, in the th century, on critical infrastructures and coupled interdependent systems (perrow, (perrow, , . we are now switching to another picture: there is no longer a mere chain of interactions, but 'piles' of activities, 'biologically' entangled and intertwined. hence, shocks trigger swells that swallow up 'totalities', beyond the idea of incremental transmission. reverberation dynamics are unfolding, not only on the ground and from one place to another, but from one network to another, one hub to another, one underlying fabric to another -locally, nationally and globally.this was a characteristic of fukushima ( ): the plant, the adjacent territory, the province, the nation and the world (with the partial loss of key electronic components, becoming more severe after the additional flooding inthailand).we have clearly switched from complex problems to something else. • from high speed to instantaneity: case studies in the th century had always underlined the speed factor, especially when it dealt with media coverage. we are now switching to something else and with a qualitative leap: in , the sars virus travelled from hong kong to toronto within a few hours, and the capital city of ontario was deep in crisis before the world health organization sounded the worldwide alert; in , wall street witnessed the 'disappearance' of billion us $ in just milliseconds. more radical still: electronic media coverage is now totally in real time, globally. during the top secret operation against bin laden, the news of the attack was already on twitter as the core strategic group was following the assault from the west wing war room; during the shootings in liege (belgium, december ), one tweet said that the gunman was in police uniform: and one sees the crowd fleeing from the police, the police not being aware of that item of news. • from local events to in-depth dislocation: this is the most decisive watershed. until now, we were focused on the specific event striking its target and the direct or indirect 'vicinity' of that target. in addition, such a strike occurred within a closed field, naturally robust and stable. studies tried to explain how the event could affect a large territory, step by step, and how the environment could finally absorb the shocks coming from the initial 'ground zero'. now, due to global interdependences, shockwaves are finding a milieu favourable to instant chain effects without 'watertight compartments'.as arjen boins underlines: 'the modern crisis does not confine itself to a particular policy area (say health or energy); it jumps from one field to the other, unearthing issues and recombining them into unforeseen mega-threats' (boin, , p. ) . moreover, fundamental fabrics (environment, economy, culture, etc.) are often in a state of preliquefaction, already very fragile.the slightest quiver can develop into extreme tremors.the event itself does not unfold in an absorbent milieu, but in a resonance chamber. this milieu is prone to triggering rogue waves through the combination-recombination of single shocks. hence, it becomes quasi impossible to trace an event on a graph, along predefined lines. the paradigm has shifted. we are just now witnessing the conflagration triggered in the arab world by a film posted on internet: a low cost weapon of mass dislocation. • from uncertainty to ignorance: there is no such thing as a risk or a crisis without uncertainty, but we are now driven into 'voids' of understanding and action that epitomize a loss of fundamental reference points. instantaneity, absorption of large parts of realities until then isolated, abundance of reverberations, rogue wave multiplication, loss of fundamental anchors and bedrocks . . . all this casts us adrift far beyond our familiar theatres of operations, be they intellectual or managerial. the challenge is no longer to grasp uncertainty at the margins of a strong core of knowledge. one is instantly confronted with the unknown, with territories where cardinal hypotheses no longer have purchase. indeed, one could argue that not one recent event adequately translates such a model. however, it is easy to plead when considering fukushima -economic and social dislocation, the environmental and energetic challenges, etc. -that the picture sketched above is beginning to emerge. the concept of 'wicked problems', introduced by rittel and webber as early as is probably the most appropriate one to translate such realities (rittel & webber, ) . when proposed, it applied to a few difficult issues; it now appears useful and even necessary to grasping the vast majority of our challenges in the crisis field.the basic idea is that the bulk of our conceptual and operational toolbox is designed to deal with tame problems: those that can be precisely defined, whose causes can be specified, that can be resolved by gathering additional data, by breaking them down into smaller problems, and by applying specific remedial techniques (camillus, ) . the basic vision is of the engineering type: the challenge is to find the best technical responses. in the conventional line of thinking, crisis issues do not trigger intractable societal discussion. wicked issues do not fall into any of these 'normal' niches, which are essential to us.there is no consensus on the definition of the problem-the very idea of a 'definition' is even irrelevant. the search for solutions never stops, there is no ultimate test of a solution since any response generates unexpected consequences, and each implemented solution has consequences that cannot be undone. every wicked problem can be considered to be a symptom of another problem. rittel and webber put it bluntly: 'the classic paradigm of science and engineering -the paradigm that has underlain modern professionalism -is not applicable to the problems of open societal systems' (rittel & webber, , p. ) uncertainty is global on every single component of the issue, with regard to all the outcomes of any action. judgment becomes crucial. fundamental values also become part of the problem, and elusive when called upon to ground a given analysis, decision or implementation. the probabilistic approach becomes ineffective. every single move triggers possible global mutations within the system and within its global context, trial and error strategies are no longer appropriate: every move is a one off move. these are indeed the core characteristics of mega crises, qualitatively different from 'traditional' eventfocused crises.the starting point can no longer be the event -the crisis field must clearly depart from the emergency domain, which has been the original niche of crisis analyses and practices. the structural issue must be the global dynamics of dislocation.we are no longer dealing with specific crises, but with crisis stages where everything is linked and mutating. dynamics are not so much mechanical chain reaction effects as engulfing global vortices. hence, we could put forward a tentative definition of the mega crisis as -the embedded engine of an overly complex world that evolves and mutates through global dynamics whose texture is made up of unstable webs of ongoing, major dislocations. (lagadec, ) since the turn of the century, and particularly since / , the motto of the crisis world has been 'think outside the box'. that already constituted a serious challenge for our descartes-inherited habits of thinking. the current reality, on all fronts, opens a new landscape: as mike granatt puts it: 'there is no box anymore' (granatt, ) . outstanding constant features have marked our reflections on the notion of crisis since the end of the s: the vigorous calling for the absolute necessity of a solid theorization so that crisis study could be recognized as a genuine science; frustration due to the extreme difficulty encountered in satisfying conventional demands to secure a grading of academic excellence; hesitation between the addition of case studies, giving way to ever more data, but poor additive knowledge and an extraordinarily difficult theorization, impossible indeed within the usual and normative codes.the whole leading to a contrasted situation made up of undeniable advances in the building of a reference body and in case-study publication, but with repeated calls for a better theorization capable of observing the canons of a noble discipline, well recognized by the scientific world. there is something pathetic in this frantic race. the demands to be satisfied in order to secure a degree of recognition are in effect essentially incompatible with the substance of the crisis phenomenon and the kind of intelligence it requires. as the issue of crises becomes increasingly more strategic, it is urgent to understand and to establish as a founding principle the fact that crisis studies cannot satisfy the requirements of classical theoretical models. crisis studies must not beg for recognition by simply trying to play into paradigms that are not and cannot be theirs; they must open their own fields and routes. if not, crisis intelligence will exhaust itself, and miss its target by the same token. this supposes, first and foremost, accepting to break, however painfully, with the past so as to escape the usual pitfalls -and to open new routes. instead of requoting here, the ever mentioned founding texts (hermann, ; béjin & morin, ; rosenthal et al., ) , rewriting pages now become classic (lagadec, , pp. - ; dayton, ) , citing the conventional references (the greek tradition, medicine, economic references, psychology, etc.), or trying to embrace the whole of organization theory literature -we will focus on a critical handful of stumbling blocks that must be decisively revisited. • definition. the literature is marked by a ritual: emphatic regret for the lack of 'really scientific' definition of the crisis concept has become a matter of course. such a preliminary confession appears to be essential to acquiring a kind of scientific royal warrant. take, for example, james a. robinson, who scathingly opens his article 'crisis' in the international encyclopedia for social sciences with: ' "crisis" is a lay term in search of a scholarly meaning' (robinson, , p. ) .the bill of indictment is well known: a term 'gutted from within' (morin, , p. ) , an 'empty shell, a ready-to-use catch-phrase' (béjin & morin, , p. ),'a convenient cliché' (starn, , p. ) ,'a vulgar and hollow little word' (morin, , p. ) ;'a very useful word in the age of mass media' since 'it creates emotion without requiring reflection'. (starn, , p. ) . nothing here is all that new. historian randolf starn points out that as early as , an italian lexicographer decried the abuse of the medical term 'crisis' (starn, , p. ) . however, such accusations and regrets are not false, especially with the growing importance of the mass media, so fond of the little word. as mike granatt ( ) put it recently: 'the word "crisis" has replaced "emergency" just because it is shorter, hence a much better fit for the media format'. but it is necessary to go beyond these basic condemnations: they tell us more about the limits of our understanding of crises than about the intrinsic limits of the concept itself. the core of crisis is precisely the fact that an event, a dynamic, does not fit into the conventional references, formats and codes -and moreover, is threatening to destroy those very references, formats and codes. demanding that crisis should fit into univocal, nonhybrid, clear-cut definitions, accepted by all and quietly settle into fixed nomenclatures, is just one more sign showing how we refuse to accept and enter crisis territory. mitroff, murat, and green ( , p. ) . are right when they underline: 'it is our contention that crisis management deals with problems that are inherently ill-structured. . . .to insist, therefore, on agreement as a precondition for studying ill-structured problems, is to ignore and to deny their basic nature. it is to misinterpret them ontologically. when crisis management experts call for agreement on the definition of basic terms, in effect, they are committing the same kind of error that we accuse practitioners of making when they ignore the complexity of crises' inherently, the crisis field is the world of the ill-structured, the intractable and the 'wicked'. even if it is useful to explore, find and use formulations that help to shape and consolidate approaches of the crisis phenomenon, it is necessary to state a preliminary and basic condition:'crisis' will resist any attempt to be 'defined'. moreover, the underlying principle to be laid down should be that any request for a definitive, clear and univocal definition of the concept should be understood as a cognitive and psychic refusal to genuinely accept and explore crisis territory. • classification. crisis literature is marked by constant efforts to deliver typologies (natural, technological, social), segmentations (internal, external, technical, organizational), time scaling (before, during, after), categories (from product defects to international crises, etc.) and myriads of crisis components, in a kind pointillist picture helping to fix at least some part of this elusive reality. all these attempts to characterize the crisis phenomenon are interesting and useful, if only they do not strive to reach an erroneous objective. in crisis territory, more than in any other,a typology can help to clarify -a little -the theatre of operations, but must not dream of locking it down. mutating, elusive realities do not let themselves be taken prisoner. in essence, crisis is, and will remain, a wild and maverick reality, impossible to understand and grasp within frameworks shaped, built and stamped to contain stable and repeated phenomena. obviously, this is extremely tiring for us, as if we were still the disciples of the naturalists of the th century: 'causes which result in effects which are rare, violent and sudden must not affect us, they are not part of the ordinary process of nature. our causes and reasons are the effects that occur each day, movements that follow one another, effects that are continually renewed and endlessly repeated' (buffon, ). • measure. crisis studies and theory of crisis management have developed in the wake of risk analysis. the conventional view is that crisis develops when risk control has failed, when 'residual risks' have taken their toll. the good news is that the whole is clearly measured, with probabilities. and crisis lies in a residual territory, limited in essence. the new theatre of operations in the risk domain compels us to step outside of this vision of 'residual accidents'.the ingredients of a new vision are pointed up, but with caution, in bernstein's ( ) 'remarkable story of risks'.the conquest of the crepuscular territory of risks has been extraordinary throughout the centuries but many 'details' that could have been ignored in the past now rush back to centre stage as we enter a much more complex, turbulent, volatile world. dice throwing follows regularities . . . 'if the dice is honest' (cardano, p. ) . nature follows regularities, but . . . 'only for most of the part' (leibnitz, p. ). 'players can anticipate processes, as long as . . . they stick to the rules upon which they agreed at the outset.' (pascal, p. ). the issue is that such difficulties, marginal in a stable, controlled and compartmentalized world, are capable of overwhelming the whole landscape in a globalized, volatile and turbulent world. this is exactly bernstein's ultimate point: the cosmology of risks, and hence of crises, could mutate since 'discontinuities, irregularities and volatilities seem to be proliferating rather than diminishing' (p. ) -which justifies the title of the conclusion: 'awaiting wildness' (p. ). if, as it is the case today, the world is mutating and is now shaped around volatility, discontinuity and nonlinearity, then our whole cosmology based on regularity measurement and modelling appears suddenly outmoded and leaves a huge theoretical void. how to think, model and handle instability, shifting dynamics and the intrinsically mutating? the age of the unthinkable (cooper ramo, ) demands a radically new science and new theoretical foundations. crisis theorists cannot develop their endeavour through normalization but only through invention. crisis is a specific 'object', which demands a specific, different, theoretical universe. but cognitive habits, academic recognition constraints, the difficulties of any discovery process and probably above all,the great ordeals that accompany any exploration of the unknown -'it was as if the ground had been pulled out from under one, with no firm foundation to be seen anywhere, upon which one could have built' (einstein,in kuhn, ,p. ) -tend to lead to 'normal thinking' rather than invention. an illuminating example of such recoil has been given in a book recently written on the subject of cataclysmic risks.the author of one of the chapters rightly underlines that, for such off-scale risks, it would be necessary to change our paradigm; but his whole contribution is strictly embedded in 'normal science, normal knowledge'. he explains: 'the challenge of existential risks to rationality is that, the catastrophe being so huge, people snap into a different mode of thinking. . . . i thought it better that this essay should focus on the mistakes well documented in the literature -the general literature of cognitive psychology, because there is not yet experimental literature specific to the psychology of existential risks' (yudkowsky, , p. ) . the fundamental challenge for academics is to understand and confront the violent negative reaction to any attempt to produce, or even to admit the necessity of, new theoretical ground and practices. just as engineers, or decision makers have difficulty in thinking outside the normally formulated hypotheses, rules and practices. the preliminary necessity is then to accept the difference between science and technique. science evolves in the unknown, and on the frontier between the known and the unknown. and there is a cardinal responsibility in science: understanding the moment when a dominant paradigm, which inspired and structured scientific and operational activity until then, begins to show signs of inadequacy. such a requirement becomes a failing if evidence accumulates to indicate that the hypotheses, visions and tools of reference no longer fit, while people stubbornly remain -out of habit, myopia or terror of change -within outmoded maps.that scientific demand is all the more extreme in the risk and crisis arena: theoretical fault lines rapidly and inevitably lead to collective tragedies. the intellectual fault line has been a decisive driver of failures and repeated fiascos in crisis territory. being a 'war behind' is a sure way of being 'defeated in every battle' as sunzi ( ) put it in his art of war. it is well known, after thomas kuhn ( ) , how such strategic vigilance with regard to tired paradigms is not the norm: 'normal science' (p. ), which imposes its norms and bans is more than reluctant to wander beyond usual closed-in and reassuring frameworks.the usual day-to-day accepted work consists of documenting 'residual ambiguities' (p. ), very far from disturbing the 'residual validity' of conventional hypotheses. the obstacle is all the more unyielding in the crisis field because, precisely, the very prospect of going beyond 'signed and sealed' schemes often triggers an instant and irrepressible need for protection and negationwhich leads to further entrenchment in conventionaloutmoded, yet so comfortable -practices and theories. within this line of thinking, any questioning of the dominant paradigm is an immediate ordeal for anyone trying to open up the approach. the burden of proof, with very rare exceptions, has to be borne by the dissenter, never by the obedient servant of the codes in place -which guarantee a solid margin of security for established theories. moreover, the dissenter will be asked to provide proofs judged and measured according to the previous paradigm -which, as kuhn underlines, is an impossible condition to satisfy. hence, the leap to the new paradigm will necessarily happen too late, when major events, impossible to hide or negate any longer, will have overwhelmed the entire field of analysis and action. in the words of hegel ( ): 'the owl of minerva takes its flight only as the shades of night are gathering'. the issue of the effective relevance of our reference models is however, crucial and must be subject to repeated auditing, all the more rigorous and frequent, given that the stakes are high, and the environments mutating and turbulent.that is precisely the case now as we enter the second decade of the st century. as thomas kuhn ( ) has underlined, when a current theory encounters more and more difficulties in its attempt to encapsulate reality, the time is ripe for a paradigm shift.this appears to be the case in the crisis world -and in management science globally. we must confront the unknown, and prepare a scientific leap, even if going beyond 'normal science' is always a difficult path to pursue. it requires the acceptance of the risk of trial and error, the acceptance of great discomfort. after all, exploration beyond known paradigms is a vertiginous affair. it requires acceptance of denial: it is impossible to convince people of the validity of a new paradigm with the arguments of the previous paradigm; moreover: any paradigm shift will be a source of anxiety, and blunt refusal is the usual initial response. there are numerous new pathways to be explored, tested, rejected or elicited. thus, in the second section we are going to modestly open up a few avenues and propose a number of signposts from the field of fractal geometry. this theoretical body of knowledge has frequently been referred to, but most often only in passing, or by way of a gloss, without a genuine understanding of the theory itself. it is important to go further, yet with caution. fractal geometry, formalized and developed by benoit mandelbrot, has shown its importance in areas subject to crisis such as finance, a domain also well known for its great complexity, volatility and discontinuity (mandelbrot, ) . it is therefore natural to wonder whether this body of concepts could be used in the field of contemporary crises, which also show these same features. this line of thought in terms of fractal geometry is not entirely new (sornette, ) , but it is worth giving it a second look as mega crises (helsloot et al., ; lagadec & topper, ) are more than ever becoming the norm. the first challenge is to master the scientific use of a foreign set of concepts in order to apply them to the field considered here. the idea is not to propose a 'miraculous key' or a ready-to-use toolbox but rather to initiate new thinking, innovative perspectives for the field of crises, through the understanding of the potentials and limitations of this approach. when one happens upon the need for a paradigm shift in the theory of complex societal phenomena, as is the case today in the theory of contemporary crises, the temptation exists to import apparently attractive, but sometimes illusory, 'theories' from elsewhere -especially from the world of physics and mathematics. in recent years, chaos theory for example has often been put forward -but, if one looks closely, its use has always been more metaphorical than genuinely useful for understanding societal phenomena. moreover, such concepts and theories cannot be extended to social sciences simply because they cannot, by definition, be translated from mathematical language to that of the social sciences (thiétart & forgues, ) . if such imports are to be made, it is only provided that: • the underlying assumptions of the imported theoretical concepts and ideas are effectively understood (beyond the mere attractiveness of the words and images used); • the contribution is not put forward as a solution or an explanation to everything, but as a means to open up new avenues that will bring new theoretical perspectives and operational avenues. in this paper, we argue that it is possible to develop the new concept of fractal crises and show how the principles it is based upon can be of real help in deepening our understanding of crisis theory and in offering ways -among other new avenues -to renew crisis management theory. we will also underline the limits of the proposition: fractal geometry cannot answer all the challenges that contemporary crises bring up and shall not be applied without a careful reflection on its practicability. mandelbrot suggested that the underlying mathematics behind market prices is based on fractals (mandelbrot, ) . a fractal can be defined as 'a geometric shape that can be split into parts, each of which is a reducedsize copy of the whole', a property called self-similarity, which itself is a subset of a larger class called invariance principles. hence, fractals and invariance principles are strongly linked. such invariance principles are beloved of physicists and mathematicians, because finding an invariant means finding a key to grasping the way the system is behaving, as this property is intrinsic to the system under study. what we will be doing here is not only basing ourselves on invariance principles, but it going beyond mandelbrot's approach by looking at how complexity can be reframed using fractals, founding our approach on the various scales and the complex dynamics that are at play in a crisis event. the existence of unchanging properties in market prices was, at first, not given much weight by most statisticians in finance. but mandelbrot managed to prove that his way of thinking was more adequate to model the behaviour of the financial markets, especially in times of crisis and high volatility. the classical financial model follows a gaussian distribution, and is therefore blind to extreme events. to be more precise, the mathematics underlying portfolio theory handles extreme phenomena with benign neglect: it regards large market shifts as too unlikely to matter or as impossible to take into account.therefore, the theoretical approach in itself does not allow working on extreme phenomena. if portfolio theory can account for what occurs % of the time in the market, the picture it presents does not reflect reality, and is biased towards a downscaling of major events. if the weather is moderate % of the time, can the mariner afford to ignore the possibility of a typhoon? the introduction of invariance principles by mandelbrot, thus proving the link between the volatility that can be tracked every day in market prices and massive market crashes, allowed a return of the exceptional to the theoretical field. the use of fractal geometry does not come closer to forecasting a price drop or rise on a specific day on the basis of past records, but it provides adequate estimates of the probability of what the market might do and allows one to prepare for the larger scale changes, for extreme events. in other words, mandelbrot came up with an approach that allowed bringing the extreme phenomena into the scientific field. it was no longer necessary to label them as 'exceptional' and leave them aside.they were taken into consideration, and as we are seeing today, % of the extraordinary can have more weight than the conventional %. the theoretical leap, not only had relevance, but it became crucial. the power of this approach and its potential application in crisis theory is to allow us to work in universes of high volatility, with extremes being the norm, multiple domains interacting at high speed, etc. these characteristics are not considered as aberrations on the margins any more, but as an intrinsic dynamic of the identity of the new paradigm. the efficient use of fractal geometry to model the extreme events in the stock market is a strong argument for applying it to the world of crises, as it also deals with complex interactions and unpredictable shocks.we, therefore, suggest here a modest contribution, and will try to show how it is possible to build a new path for crisis theory in terms of fractal geometry, and in turn build a new path to crisis management through the search of key parameters that we call 'invariants' as they will prove to be a useful toolkit for grasping a large spectrum of crisis events. looking for invariants not only means looking for elements that are common in different crisis events, it also means being able to understand what remains unchanged and what is dynamic, what is part of the solution and what is part of the problem. our new conceptual approach is based on looking for underlying principles that allow a better understanding of global catastrophic events, in the same way that invariants can represent fundamental keys to understanding fractals and volatility. a number of methods are available for identifying complex realities in terms of fractals. in most cases, fractal theory is described through invariance principles, i.e., considering what is common in universes where crises happen on different scales. but we can also go in complementary directions, where one seeks to understand the specific properties of each level. invariants are then the key to analyzing the more important interactions, the potential tipping points, the weak signals that allow one to anticipate possible turbulence, etc. many papers have documented how the world has become global or interconnected, but very little exists on a deeper conceptualization of what that implies.the introduction by n. taleb ( ) of the concept of black swans, i.e., the rare events that have dramatic consequences, was a first step towards making people understand that rare does not mean inexistent and that a rare but destructive event is not to be neglected. although his point was a very interesting conceptual advancement, it did not in itself imply a rethinking of how the world has changed. it was merely remembering people that gaussian statistics are just an approximation of reality, the tip of the iceberg. a useful approximation, as long as everything is normal, i.e. in the smooth %. a precise definition of a crisis has always been difficult to give. our approach allows us to go beyond classic definitions, by approaching crisis events as the transition from one state of equilibrium to another through a massive disruption. our contribution here is a new way of thinking, based on a simple, new, principle: looking for fundamental principles of action and identifying their effects.we aim to show that invariants are a general characteristic of modern crises, a pattern that has been long hidden in the fabric of crises and that those invariants have very observable effects, some of which are already well documented, as we shall see. the path we are suggesting is not the only possible one, and although it has some very appealing features, it does suffer numerous limitations that we shall explain in the next section. our first steps into this new world imply a new set of tools to characterize crises. we will be looking at different features of crises, not limiting ourselves to invariance principles but going beyond that by looking at the intrinsic complexity of crises and its key parameters: global effects, high speed, deep complexity and weak signals. the shift from small, localized events to global impact catastrophe has become a common feature of modern crises.this widespread feature is commonly referenced in the literature (körnert, ) as the 'domino effect'. we can for example think about the fukushima event and its impact on world energy policies, but numerous other examples can be documented. modern means of communications and transportation has shortened the characteristic time of all events to its strict minimum. trading is reduced to the millisecond (high-frequency trading), communications from one side of the world to the other are almost instantaneous, etc. in turn, crisis has spread from a short-term event to a long-term impact crisis. the observable effect is most commonly known as the 'magnifier effect', for example in finance where microsecond trading (birraux, ) leads to market crashes (the example given earlier of the th may market crash being a perfect illustration of it).any discrepancy, any error, any rigidity propagates extreme volatility and turbulences to the entire deck of cards. the third feature we are introducing is rank invariance, which is linked to how individuals act one towards the other. it is very similar to the domino effect, but this time it is not places that are affected, but people through their interactions.this invariance explains why modern crises can start by impacting one single individual on one side of the world and turn it into a global changing event. the observable consequence of this invariance principle is commonly documented as the 'aggregation effect'.the best recent example of such an effect is mohamed bouazizi's self-immolation that led to the arab spring (mc kay, ). the fourth characteristic at play is sense-making (weick, ) invariance. understanding this key prin-ciple allows a better understanding of why, during modern crises, the loss of control affects equally the isolated individual, who does not understand what is happening, and the state leaders, who fail to grasp the magnitude of the ongoing crises, leading to global dislocation.this sense-making invariance is best illustrated (smallman & weir, ) , by the well-known blur effect, which has been used to explain how absurd decisions were taken not only by common individuals but also by eminent leaders. it leads to what we like to call 'information asymmetry', i.e., the loss of information when one goes up or down the decision ladder, which we shall explain more in depth in the next section. with this set of rules, we have built a grammar of reading that provides common guidelines for crisis theory, relying on a small number of dimensions (space, time, rank and sense).this classification allows for more powerful tests to establish a generic mapping of crisis and avoids entering immediately into hierarchical classifications, which cannot grasp the power of systemic crises. moreover, instead of building a theory designed for the 'normal world' and trying to map it to crisis situations, we immediately built its roots a vision that contains complexity. it goes far beyond taleb's principles and the possibility of a black swan. here, we are in a world where normality is not the norm, where the black swan is no longer the outlier and where the search for invariants is especially relevant in a world built from variability and stress. we have laid the ground to a new understanding of crisis theory,showing that well-documented phenomena can be linked to a set of simple principles that can trace stability and instability in the context of crisis events, which is already a big step forward.this new conceptualization of crises can bring theoretical foundations to crisis management techniques that are already being implemented and can help to provide a deeper understanding of conceptual and practical problems. the power of the fractal approach is that it allows you to get rid of a linear and stable vision of the world, an approach inconsistent with the field of crisis.as long as it remained in the realm of low scale emergency it was possible to keep our unified approach, where consequences are additive and relatively simple to control.yet we must go beyond simple adjustment when we enter global, volatile worlds. fractal theory opens up the possibility of envisioning and navigating multiple, unsettled domains, multiple layers and dynamics. . from a spatial point of view, it becomes possible to work separately on the hyperlocal, local, regional, national, continental and global.we can multiply the fields considered, each with their relevance, specificity and dynamics.we work at the outset, where the vision is plural and where one must be able to operate multiple levers of action at the same time. . from a temporal point of view, it becomes possible to work on speed and evolutions, even mutations, in new ways. for example, instantaneous dynamics (type social networks) and fast dynamics (radio and television), can all be linked to the same building blocks. one is not limited to a single timeline approach, but is allowed to immediately think of many overlapping timelines that have different dynamics and fundamental building blocks such as contradictions, oppositions, factors of evolution and mutations, that blur the view of actors who have different perspectives. . from an actor's point of view, the individual, family, organization, country, etc., find their place, taking into account that everyone has different information, different perceptions of the same information or different information. . from the point of view of 'making sense', one can also escape reductive simplistic visions and make room for multiple subjective 'sense making processes'. these are just a few well-known dimensions, but there could be many others: the multiplicity, interaction and volatility of fields and dimensions are basically included in the code of the fractal approach. let us work out an example where information is minimal, where there are only weak, wild signals, where there is no warning light, no simple data to analyze and where only vigilance, examination of blind spots and informed assumptions based on fractal crisis theory can give a clue as to what the dynamics at play is really is about. for decades, disaster literature has highlighted the limitations and problems hazards caused by the 'command and control' vision, the centralized top-down approach (rodriguez, quarantelli, & dynes, ; drabek, ) . the approach developed here escapes from these dilemmas and conflicts of vision.there is no overriding principle that is able to support a global dynamic in which each component has autonomy, an impulse and a specific variability. one must go beyond top-down and bottom-up; simply because as information gets diluted and transmitted along the decision chain, it gets distorted and reinterpreted. the specificity of a crisis event is the amount of distortion that a 'piece of information' (in its broad meaning) can suffer: during a crisis event, one piece of information is received differently by the actors (partial transmission, mutation, distortion, etc.) and every single actor interprets it differently based on his local reality and acts differently. thus, talking about bottom-up or top-down approaches is largely insufficient because there are multiple realities at play. the common practice has most often been to centralize the decision-making process and to concentrate on a top-down approach, with the strategic oversight of the highest people in the hierarchy often conflicting with what is happening on the ground.that practice in a crisis situation can be easily understood as a response to the top-down approach needed for our judicial and governance system which needs to have a clear chain of command to attribute responsibilities during and after the crisis. one of the most disturbing facts during a crisis event is how information, or misinformation, circulates and propagates. when a leader at the top of the decision chain tries to give an order to someone at the other end of the chain, he thinks that his decision can and will be understood. but in reality, while his decisions seem to be properly transmitted, with everyone in the decision chain thinking they have all understood the same thing, they all end up interpreting the decision in different ways, thus leading to incoherent, conflicting and sometimes absurd action. fractal crises theory teaches us that crises happen on all scales and that the built-in invariants imply that leaders and decision makers will be impacted by effects just as those who are closer to the situation area.that is to say, taking the decision power away from those closest to the ground, best able to evaluate their needs, and giving it to people far from ground level and supposedly less impacted by the crisis is a fallacy. what is at play here is the conflict between the way decisions circulate and the way information flows. that is why a full top-down or a full bottom-up approach cannot work. it all happens exactly as for a fractal pattern: every time you switch to a different scale, you have the sensation of seeing the same thing, but in reality the resolution has changed and what looks the same is in fact different. the blur effect created by sense-making invariance forbids someone on one step of the decision ladder to communicate freely with someone on another step. as fractals teach us, the information flowing, at any scale, that is to say going up or down the ladder, gets distorted. what one gains in overview one loses in micromanagement, and therefore, one interprets information received in a different way. the current situation, with the decision process being top-down and the information flow going both ways with losses, is incoherent.this realization means that there is something wrong with the conception of crisis management where decisions can be taken on one end of the decision chain to be put into action by someone else at the other end of the chain. we have decided to call this situation, where no one has access to the full, undistorted deck of cards, information asymmetry. it is well known that information is a key to the resolution of any crisis, not only to reduce its impact but also in terms of communication to the public, hence such asymmetry is not a minor problem. we argue that one must not restrict oneself to a top-down approach and open one's minds to broader perspectives. in other words, if the top-down approach allows a better distribution of responsibilities for the after-crisis, it completely destroys efforts to limit the impact of the crisis. thus, fractal crisis theory pleads for a more pluralistic approach based not only a selective distribution of responsibilities and better trust in the personnel on the ground. the goal is, therefore, to grasp the information as early as possible, at its point of origin, and to dispatch it to the one closest to it. it should not have to go up the decision ladder, as the information going up and the decision going down would both get distorted. thus, the one in charge of dealing with the new information would be the one that has had access to the least disturbed information. dispatching the information would require an 'information over-watch' team.this special group would be in charge of collecting all new information, evaluating its credibility and importance, and delivering it with the appropriate context to the right person on the ladder. this organizational innovation would thus reduce the loss of information from bad contextualization or improper priority rating. we here, base our work on previous key approaches such as that developed by mike granatt (granatt & paré-chamontin, ) , going beyond the top-down/bottom-up discussion. each layer has its own dynamics; none can have a steering role and one needs to step back to understand the complexity of the system.we need people who can master the broad view and act within an intensely connected and susceptible world. thus, the decision shall then be taken by the person who receives the information, whatever his or her position in the current 'normal' decision process. the role of this information over-watch team is therefore crucial. in our system, responsibility and decision making would therefore be distributed throughout the decision chain, and the one closest to the new information is the one that acts according to it. the goal is not to produce people who can apply pre-planned answers; we need people who expect and embrace the new and the novel. we need them to accept strange signals and 'impossible' scenarios, to enter strange seas without being paralyzed by the absence of maps. we need people who relish the challenge of creative thinking and action, even in the most inconceivable and rapidly developing contexts. the concept and method of the rapid reflection force (béroux, guilhou, & lagadec, ; béroux, guilhou, & lagadec, ) has been suggested, developed and tested to help organizations overcome such challenges. a specific group of people are asked to clarify the high complexity and volatility of a situation, and to suggest new visions and paths of action enabling the whole system to better navigate the turbulence. clearly, these new paths into the unknown are still in a very preliminary form. every single facet of crisis theory and management should now be revisited within this framework of fractal theory. for instance, dimensions such as leadership, signal, emergent behaviour, information and communication, sense-making, etc. should now be re-explored. it will take time before we develop more precise specific theories and practical knowledge on all these facets. it does not mean that our more conventional approach to crisis management should be forgotten. our classical knowledge is still valid for relatively limited crises, and should be used. it would be dangerous to switch too swiftly to the mindset we suggest. but we must also underline that it will remain difficult to develop and to strengthen the view developed in this paper. such perspectives are and will remain a source of very deep and severe discomfort. our deep seated cartesian culture is very strong and stronger still in times of crisis, as we tend to immediately reject complexity by calling it 'chaotic'. many decision makers might even find such perspectives disturbing. hence, the idea that we should prepare future leaders to open their minds to such new avenues. if we can overcome these obstacles, we will have embarked upon the exploration of unknown lands: it will remain very difficult, but at least we will be on a relevant track. the world of crises is facing extreme upheavals. it is not just an extension of accidental phenomena within a system; we are confronted with extreme turbulence, in global and highly unstructured environments. rude surprise will be the name of the game (laporte, a,b) . our crisis management theories and practices were not designed to grasp such 'wicked' environments: they are largely outdated. the first section of this paper documented this challenging situation -in the field as well as in the theoretical arena. in response, there is a growing need for a theoretical leap -obviously resulting from the conjunction of a diversity of inputs.the objective of this contribution has been to consider the possibilities offered by the fractal geometry as a candidate to help those in charge of navigating in unknown, extremely turbulent environments.the path we suggest is one of many ways that can be taken on the road to crisis management theory and operational crisis management. the ideas underlying mandelbrot's mathematical work can be effectively used to better describe modern crises as analogous to fractals, and the underlying invariance principles can be mapped into well-known effects in crisis management. yet beyond mandelbrot's own work, the crucial advance offered by fractal theory is the possibility to envision, capture and handle very unstable, blurred and hypercomplex states of the world. a lot remains to be done to test the feasibility of this approach, to assess what it can bring to the field, and last but not least, to detect the limitations of this line of thought.we are only at the beginning of the intellectual brainstorming required by the age of mega crises. on the research agenda, we will modestly plead for launching research projects -case studies, training methods, operational guidelines, theoretical lines of thought, seminars and workshops -to shed some additional light and to promote innovative knowledge in the field of emerging mega crises. after all, tackling the unknown is the very object of research and theory. the essence of decision: 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technologies the next catastrophe -reducing our vulnerabilities to natural, industrial, and terrorist disasters response to social crisis and disaster dilemmas in a general theory of planning crisis handbook of disaster research managing crises -threat, dilemmas, opportunities coping with crises.the management of disasters, riots and terrorism communication and cultural distortion during crises', disaster prevention and management critical phenomena in natural sciences : chaos, fractals, self-organization and disorders « métamorphose d'une notion. les historiens et la «crise the art of war, library of chinese classics the black swan -the impact of the highly improbable the first hours.a comprehensive guide to successful crisis communications, basil blackwell science and its limits: the regulator's dilemma' cognitive biases potentially affecting judgment of global risks key: cord- - jslid authors: el sayed, khalid a. title: natural products as antiviral agents date: - - journal: nan doi: . /s - ( ) - sha: doc_id: cord_uid: jslid since the ancient times, natural products have served as a major source of drugs. about fifty percent of today's pharmaceutical drugs are derived from natural origin. interest in natural products as a source of new drugs is growing due to many factors that will be discussed in this article. viruses have been resistant to therapy or prophylaxis longer than any other form of life. currently, there are only few drugs available for the cure of viral diseases including acyclovir which is modeled on a natural product parent. in order to combat viruses which have devastating effects on humans, animals, insects, crop plants, fungi and bacteria, many research efforts have been devoted for the discovery of new antiviral natural products. recent analysis of the number and sources of antiviral agents reported mainly in the annual reports of medicinal chemistry from to indicated that seven out of ten synthetic agents approved by fda between - , are modeled on a natural product parent. it has been estimated that only - % of the approximately , species of higher plants have been systematically investigated for the presence of bioactive compounds while the potential of the marine environment has barely been tapped. the aim of this review is to provide an overview on the central role of natural products in the discovery and development of new antiviral drugs by displaying structures of plant, marine and microbial origin that show promising in vitro antiviral activity. since the ancient times, natural products have served as a major sourc e of drugs. abou t fift y percen t o f today' s pharmaceutica l drug s ar e derive d from natura l origi n [ ] . th e growin g interes t i n natura l product s a s a source o f ne w drug s ca n b e attribute d t o man y factor s includin g urgen t therapeutic needs , th e wid e rang e o f bot h chemica l structure s an d biological activitie s o f natura l secondar y metabolites , th e adequac y o f bioactive natura l product s a s biochemica l an d molecula r probes , th e development o f recen t technique s t o accuratel y detect , isolat e an d structurally.characterize th e bioactiv e natura l product s an d advance s i n solving th e deman d fo r suppl y o f comple x natura l product s [ ] . historically, th e majorit y o f th e natura l product-base d drug s includin g cyclosporine, paclitaxel and camptothecin derivatives were first discovered by traditiona l cell-base d in vitro assay s befor e thei r rea l molecula r biological targets were identified [ ] . these cellular biological responses of natural products are likely to be associated wit h the inherent properties of secondary metabolites for the defense of their producing organisms [ ] , infectious vira l disease s remai n a worldwid e problem . viruse s hav e been resistant to therapy or prophylaxis longer than any other form o f lif e due to their nature because they totally depend on the cells they infect fo r their multiplication an d survival. this peculiar characteristic has rendered the developmen t o f effectiv e antivira l chemotherapeuti c agent s ver y difficult. currently , there are only few drugs available for the cure of viral diseases includin g acyclovi r ( ) , the know n antiherpeti c dru g whic h i s modeled o n a natura l produc t parent . i n orde r t o comba t viruse s whic h have devastatin g effect s o n humans , animals , insects , cro p plants , fung i and bacteria, many research efforts hav e been devoted for the discovery of new antiviral natural products. although the search for naturally occurrin g products whic h ca n interfer e wit h vira l infection s bega n wit h th e successful isolation of antibiotics from microorganism s but it has not been as intensive a s that of synthetic antiviral agent s [ ] . this is mainly du e to the tendenc y o f most virologists wh o adop t a rational desig n o f antivira l agents rathe r tha n towar d empiricis m especiall y wit h th e progres s i n knowledge o f vira l replicatio n [ ] . moreover, ther e ar e som e problem s arising from the screening of crude extracts, as well as with the purificatio n and identificatio n o f the antivira l component s fro m thes e crud e extracts . these problems became less intense with the recent advances in differen t chromatographic an d spectroscopi c technologies . man y natura l an d synthetic compound s wer e foun d t o sho w in vitro antivira l activit y bu t were much les s effective whe n tested in vivo. thi s could be attributed t o difficulty i n dru g transportatio n t o th e cell s o f th e infecte d tissu e especially i f thes e tissue s becom e inflamme d du e t o infection . man y antivirally activ e compound s ar e to o toxi c fo r therapeuti c applications . however, natura l product s remai n th e bes t resourc e fo r chemicall y diversed ne w lea d entitie s tha t coul d serv e fo r futur e developmen t a s potent and safe antiviral agents. recent analysis of the number and sources of antivira l agent s reporte d mainl y i n th e annua l report s o f medicina l chemistry fro m t o indicate d tha t seve n ou t ofte n syntheti c agents approve d b y fd a betwee n - , ar e modele d o n a natura l product paren t [ ] . thes e drug s are : famciclovi r ( ) , ganciclovi r ( ) , sorivudine ( ) , zidovudin e ( ) , didanosin e ( ) , zalcitabin e ( ) an d stavudine ( ) [ ] . the aim of this review is to provide an overview on the central role of natural products in the discovery and development of new antiviral drugs. the original latin meaning of "virus" is "poison", "venom" or "slime" [ ] . the word "virus " was also used figuratively i n the sense of "virulen t or bitter feeling", "stench" or "offensive odor " [ ] . in the late s, the term "virus" was bestowed on a newly discovered class of pathogens, smaller than bacteria being studied by louis pasteur and others of that era [ ] . as late as , "virus" was defined a s "the poison of an infectious diseas e especially foun d i n th e secretio n o r tissue s o f a n individua l o r anima l suffering fro m infectious diseases [ ] . in the early decades of the twentieth century, viruses were identified a s infectious agent s that were filterabl e and invisibl e i n the ligh t microscop e whic h superficiall y distinguishe d them from most familiar microorganisms [ ] . today, viruses are defined as noncellular infectiou s agent s that vary in size, morphology, complexity , host range and how they affect thei r hosts [ ] . however, they share three main characteristics in common: a) a virus consists of a genome, either rna o r dn a cor e (it s geneti c material ) whic h i s surrounde d b y a protective protei n shell . frequentl y thi s shel l i s enclose d insid e a n envelope (capsid) that contains both proteins and lipids, b) a virus can be replicated (multiplied ) onl y afte r it s genetic materia l enter s a host cell . viruses are absolutely dependen t o n the host cells' energy-yieldin g an d protein-synthesizing machinerie s an d henc e the y ar e parasite s a t th e genetic level, c) a virus's multiplication cycle includes the separation of its genomes from its protective shells as an initial step [ ] . when a virus is outside the host cell, it is considered no more alive than a chromosome [ ] . the interval between successive mitosis of the individual cell is divided into three periods [ ] : -th e gl perio d precedes dna replication. its average duration is hours. -th e s period during which dna replicates. its average duration is hours. -th e g period i n which the cell prepares for th e next mitosis. its average duration is hours. rna an d protei n ar e no t synthesize d whil e mitosi s proceeds , i.e. , during th e metaphas e whic h i s betwee n an d g l period s bu t ar e otherwise synthesize d throughou t th e multiplicatio n cycl e [ ] . nongrowing cell s are usually arreste d i n the gl period ; the resting stat e i s referred t o a s go. under norma l grov^h conditions , cells o f a growing culture multiply in an unsynchronized manner, hence cells at all stages of the cycle are present. the aging of cells starts after abou t passages by d slowing their growth rate. the amount of time they spend in go after eac h mitosis gradually increases . the chromosomal complemen t change s fro m normal diploi d t o aneuploid pattern , supernumerar y chromosome s an d i t finally fragmente d an d th e cel l dies . malignan t tissue s giv e ris e t o aneuploid cel l line s tha t hav e infinit e lif e span s an d ar e know n a s continuous cell lines. the main feature of normal animal cell is its compartmentalization [ ] . the dna o f the animal cel l i s restricted to the nucleus at all cell cycle stage s except durin g metaphas e whe n no nucleus exists . the synthesi s o f rn a occurs i n the nucleu s an d mos t o f i t remains there , but messenge r rn a and transfe r rn a migrat e t o th e cytoplasm . ribosoma l rn a i s synthesized i n th e nucleolus ; th e tw o ribosoma l subunit s ar e partl y assembled in the nucleolus and nucleus then migrate to the cytoplasm. all protein synthesi s procee d i n th e cytoplasm . th e mitochondria , whic h i s located onl y i n th e cytoplasm , contain s dna-s , rna -an d proteinsynthesizing system s of their own [ ] . viruses replicate in different ways . in all cases, the viral dna or rna i s copied repeatedly. viral proteins are synthesized inside a suitable host cell where man y ne w vira l particle s ar e assemble d [ ] . generall y viruse s replicate through the following stage s [ , , ] , whic h ar e incorporate d int o th e host' s plasm a membrane. -thes e viral nucleic acids, enzymes and capsid proteins are assembled into ne w vira l particle s (genomes ) togethe r wit h thei r associate d rna or dna polymerase. -th e newly formed viral particles are released from the infected cell. viruses usually replicat e by lytic or temperate pathways. in the lytic pathway, stages - from above proceeds quickly and the virus is released as the host cells undergo lysis, ruptures and dies after los s of its contents. in temperat e pathways , th e viru s doe s no t kil l th e hos t cel l bu t th e infection enter s a period of latency, in which viral genes remain inactive inside th e hos t cell . i n som e case s o f latenc y th e vira l gene s becom e integrated into the host's dna, replicated along with it and passed along to all daughter cells. in time, damage to the dna or some other event may activate transcription of the viral genes therefore new viral particles can be produced an d infected cell s are destroyed [ ] . proposed targets of some specific antivira l chemotherap y ar e illustrate d i n figur e and ca n b e summarized as [ ] : -attachmen t (adsorption) of the viral particle to the host cell. -penetratio n of the host cell by infectious viral particles. -particle s uncoating, release and transport o f viral nucleic acid and core proteins. -nuclei c acid polymerase release and/or activation. -translatio n of m-rna to polypeptides which are early proteins. -transcriptio n of m-rna. -replicatio n of nucleic acids. -protei n synthesis (late proteins). -vira l polypeptides cleavage into useful polypeptides for maturation. -morphogenesi s and assemblage of viral capsids and precursors. -encapsidatio n of nucleic acid. -envelopment. -release. proteins represen t th e mai n vira l component . protein s ar e th e sol e constituent o f capsids, the major componen t of envelopes and also they are associated with the nucleic acids of many viruses as core proteins [ ] . viral proteins have a wide range of molecular weight ranging from , - , daltons. viral proteins also vary in number, some viruses posses as few as three species while others contains up to protein species. all members o f th e sam e viru s famil y displa y almos t th e sam e highl y characteristic electrophoretic protein patterns [ ] . glycoproteins: vira l envelope s usuall y contai n glycopotein s i n th e form o f oligomeric spike s or projections. th e carbohydrate moietie s of glycoproteins are formed o f oligosaccharide ( - monosaccharide units) which are linked to the polypeptide backbone through n-and o-glycosidi c bonds involvin g asparagin e an d serin e o r threonine , respectively . thei r main component s are : galactos e an d galactosamine , glucos e an d glucoseamine, fucose , mannos e an d siali c aci d whic h alway s occupie s a terminal position [ ] . example of some viral proteins with specialized functions are : hemagglutinins: man y anima l viruse s (e.g. , ortho -an d paramyxoviruses) agglutinate the red blood cells of certain animal species. this mean s tha t thes e re d cell s contai n receptor s fo r certai n surfac e components of viral particles that act as cell attachment proteins which are glycoproteins and known as hemagglutinins. viral hemagglutinins could be used in their quantitative measurement [ ] . enzymes: anima l vira l particle s ofte n contai n enzyme s (tabl e ) . these enzymes are virus-specific. i n addition to the enzymes summarize d in tabl e , viruse s ofte n contai n othe r enzymes . amon g the m ar e th e enzymes tha t modif y bot h end s o f m-rn a molecule s synthesize d b y their cappin g enzyme s an d poly(a ) polymerases . protei n kinases , deoxyribonucleases, dna-dependen t phosphohydrolase s an d topoisomerases are also often present in viruses [ ] . homeostasis of cell numbers in multicellular organisms is maintained by a balance betwee n cel l proliferatio n an d physiologi c (programmed ) cel l death. apoptosis is a process by which cells undergo physiologic death in response t o a stimulu s an d i t i s a predictabl e serie s o f morphologicall y defined events . it is divided int o two stages namely, the breakdown of the nucleus an d alteratio n o f th e cel l shap e an d th e plasm a membran e permeability. th e consequence s o f apoptosi s ar e th e fragmentatio n o f nuclear dna , the zeiosi s (boiling ) o f the cytoplas m associate d wit h th e blebbing and increased granularity of the plasma membrane and fracturin g of the cel l int o subcellula r dna-containin g apoptoti c bodies . apoptosi s process i s different fro m necroti c cell death by involvement o f lysosoma l enzyme leakage into the cytoplasm, the swelling of the cell and the actual rupture of the plasma membrane. necrosis is often induce d by agents that affect membran e integrity , generalize d protei n synthesis , o r energ y metabolism [ ] . apoptosis ca n b e induced*b y a variet y o f stimuli , e.g. , steroids, cytokines, dna-damaging agents , growth factor withdrawa l an d in case o f t or b cells, antigen-receptor engagement . apoptosi s i s also a mechanism b y whic h cytotoxi c lymphocyte s kil l thei r targets . man y viruses ca n induc e apoptosi s i n infecte d cell s whil e man y othe r viruse s especially transformin g viruses , ca n inhibi t apoptosi s an d allo w fo r cel l transformation. th e nuclea r change s durin g apoptosi s induc e chromati n [ ] . viruses caus e severa l hundre d infectiou s disease s t o man y plant s afte r successfully penetratin g their cell walls, reducing the yield of a variety o f crops includin g tobacco , potatoes , tomatoes , a s wel l a s man y othe r vegetables, inducin g seriou s economi c damages . som e insect s tha t fee d plants assis t i n vira l infection . vira l particle s ma y b e clingin g t o thes e insects' piercing or sucking devices and when these devices penetrate plant cells, infectio n occurs . many anima l viruse s infec t human s an d animal s causin g severa l seriou s diseases. tabl e present s a summar y o f som e anima l viruse s an d th e diseases they induce. viroids ar e plant pathogen s whic h consis t o f naked strand s o r circle s o f rna with no protein coat. viroids are mere snippets of genes smaller than the smalles t know n vira l dn a o r rn a molecul e an d the y ca n hav e damaging effect s o n citrus , avocados , potatoe s an d othe r cro p plants . apparently, enzyme s alread y presen t i n a hos t cel l synthesiz e viroi d rna then use this new viroid rna as a template for building new viroids. some unidentified infectiou s agents cause some rare fatal diseases of the nervous system including scrapie in sheep and kuru and crutzfeldt-jaco b (mad cow ) diseas e i n humans . probabl y thes e disease s ar e cause d b y infectious protei n particles , tentativel y name d prions . prion s migh t b e synthesized accordin g t o informatio n i n mutate d genes . researcher s studying scrapie , hav e isolate d th e gen e codin g fo r altere d form s o f a protein in infected cells [ ] . viruses are either measured as infectious units, i.e., in terms of their ability to infect, multipl y an d produce progeny or as viral particles, regardless of their function a s infectious agents [ ] . titration mean s th e measuremen t o f the amoun t o f viru s i n terms o f th e number of infectious unites per unit volume. plaque formation [ ] monolayers of susceptible cells are inoculated with small aliquots of serial dilutions o f th e viru s suspensio n t o be titrated. wheneve r vira l particle s infect cells, progeny virus particles are produced, released and immediately infect adjoinin g cells . this process i s repeated until after - incubatio n days o r more . area s o f infecte d cell s develo p plaque s tha t ca n b e see n with a naked eye. agar is frequently incorporate d i n the medium to ensure that th e liberate d progen y viru s particle s i n th e mediu m d o no t diffus e away an d initiat e separat e o r secondar y plaques . the infecte d cell s mus t differ i n some recognizable manner from non infected ones , i.e., they must be completely destroyed, become detached from the surface o n which they grow o r possess stainin g properties differen t fro m thos e o f normal cells . the mos t commo n metho d t o visualize plaques i s to apply neutra l re d o r crystal violet to the infected cel l monolayers and then counting the number of no n staine d area s [ ] . titer s ar e expresse d i n term s o f numbe r o f plaque-forming unit s (pfu ) pe r milliliter . ther e i s a linea r relationshi p (linear dose-response curve ) between the amount of virus and the numbe r of plaque s produce d whic h indicate s tha t eac h plaqu e i s produced b y a single vira l particle . th e viru s progeny i n eac h plaqu e ar e clones . viru s stocks derived fro m singl e plaques are named "plaqu e purified " whic h i s important i n isolatin g pur e viru s strains . plaqu e formatio n i s th e mos t desirable metho d o f viral titration becaus e i t is economic an d technicall y simple. however, not all viruses can be measured thi s way due to lack of host cells that can develop the desired cytopathic effects (cpe) . many anima l viruse s ge t adsorbe d b y red bloo d cell s (rbcs ) o f variou s animal species. each viral particle is a multivalent, i.e., it can adsorb more than on e cel l a t a time . i n practice , th e maximu m numbe r o f cell s wit h which any particular virus can combine is two since rbcs are bigger than viral particles. in a virus-cell mixture in which the number of cells exceeds the number of viral particles, the small number o f cell dimer that may b e formed i s generally undetectable . if the number o f viral particles exceed s the number of cells, a lattice of agglutinated cells is formed tha t settles out d in a characteristic readily distinguishable manner from th e settling pattern exhibited b y unagglutinate d cell s [ ] . hemagglutinatio n assa y i s th e determination o f the virus that will exactly agglutinate a standard numbe r of rbcs. because the number of viral particles required fo r this is readily calculated (slightly higher than the number of cells), hemagglutination is a highly accurate and rapid assay. in vitro antiviral screening assays [ , ] the vira l infectivit y i n culture d cell s i s determine d durin g viru s multiplication i n the presenc e o f a singl e teste d compoun d o r extrac t o r after extracellular incubation. current antiviral chemotherapy [ , ] research i n antiviral chemotherapy starte d around early ' s when the search fo r anticance r drug s revealed severa l new compounds tha t inhibi t viral dn a synthesis , e.g. , th e pyrimidine analo g idoxuridin e whic h wa s later approve d a s a topica l treatmen t fo r herpe s keratitis . sinc e then , research effort s wer e focused o n both purine and pyrimidine nucleosid e analogs [ ] . with the emergence of aids epidemic, research on antiviral generally an d specificall y anti-hi v becam e highes t priority . man y o f these retrovirus proteins have been purified and characterized for the sake of designing drugs that would selectively inhibit some critical enzymes of hiv such as reverse transcriptase and protease which are required for the final packaging of this virus particle. -zidovudin e ( ) (previousl y azidothymidine , azt ) i s a deoxythymidine analo g tha t als o requires anaboli c phosphorylatio n for activation . i t competitivel y inhibit s deoxythymidin e triphosphate fo r th e rt . i t als o act s a s a chai n terminato r i n th e synthesis of pro viral dna. it is active against hiv- , hiv- and the human t cell lymphotropi c viruses . resistance to occurs due to mutation in rt gene. didanosine ( ) i s a syntheti c analo g o f deoxyadenosine . i t i s anabolically activated to , -dideoxyadenosine- -triphosphate which inhibits viral replication as . resistance is typically associated with mutation at codon . zalcitabine ( ) is a pyrimidine nucleoside that inhibits replication of hiv- in a similar mechanism to . mutation at codon induces resistance which is associated with the decrease in susceptibility to and . -stavudin e ( ) is a thymidine analog that also requires a metabolic activation as that of . it is active against hiv- . -lamivudin e ( ) is a nucleoside analog which in vitro inhibits hiv- and hbv . it inhibits hiv-rt and shows synergistic effec t wit h against hiv- . it requires metabolic phosphorylation a s that of . high level of resistance is developed by mutation at codon . -indinavi r is a specific inhibitor of hiv- protease which is essential for th e production o f mature and infectious virions . it i s currently clinically approved for treatment of hiv- infections. -ritonavi r is an inhibitor of hiv protease with high bioavailability. it is metabolized by the hepatic p cytochrome oxidase system and hence suffers from several drug interactions. -saquinavi r is a synthetic peptide-like analog that inhibits the activity of hiv- protease and prevents the cleavage of viral polyproteins. -ribaviri n [ ] i s a guanosin e analo g tha t i s intracellularl y phosphorylated b y the host cell's enzymes . despite its mechanism is not yet fully elucidated , it apparently interferes with the synthesis of guanosin e triphosphat e t o inhibi t cappin g o f vira l mrn a an d some viral rna-dependent polymerases. its triphosphate derivative inhibits the replication o f a wide range o f rna and dna viruses including influenz a a and b , parainfluenza, respirator y syncytia l virus (rsv), paramyxovirus, hcv and hiv- . four basi c approache s ar e conducte d fo r plan t selectio n fo r antivira l screening assays : -rando m collectio n o f plant s followe d b y mas s screening. -ethnomedical approach. -literature-based follow up of the existing leads. -chemotaxonomic approac h [ ] . the second and third approaches ar e th e mos t favore d one s becaus e o f thei r cost-effectiv e applicability. the selection based on folkloric use proved five times higher percentage o f active leads than other approaches. the random approach usually affords mor e novel compounds with antiviral activity. combining ethnomedical, phytochemical an d taxonomical approache s is considered the best compromise. different cel l culture-base d assay s ar e currentl y availabl e an d ca n b e successfully applie d fo r plan t extract s an d pur e compounds . antivira l agents tha t interfer e wit h on e o r mor e vira l biosyntheti c dynami c processes are good candidates as clinically useful drugs . virucidal agents that extracellularl y inactivat e viru s infectivit y ar e rathe r candidate s a s antiseptics. th e ke y factor s tha t determin e th e selectio n o f th e assa y system are : simplicity , accuracy , reproducibility , selectivit y an d specificity [ ] . after evaluatio n o f th e antivira l potenc y o f a teste d compound along with its cytotoxicity, the therapeutic index in a given viral system i s calculated. th e therapeutic inde x i s defined a s a ratio o f the maximum drug concentration at which % of the normal cells grovrth is inhibited to the minimum drug concentration at which % (sometimes or %) of the virus is inhibited. the relative potency of a new antiviral agent should be compared with an existing approved drug. in vivo testing of any new in vitro active antiviral agen t i s considered th e key ste p befor e an y huma n clinica l trials . thi s mode l shoul d predic with an animal's metabolic processes. -provin g tha t the compoun d wil l resist an d will no t adversel y affec t the immune system [ ] . two usefu l anima l model s ar e usuall y employed : heterologu s o r homologus. in heterologus systems, a disease is induced by a virus from a n animal origi n i n an experimenta l anima l tha t mimic s th e huma n disease . several review s hav e bee n publishe d dealin g wit h natura l productsderived antivira l compound s [ , , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . presently, there ar e only tw o plant-derived compounds under clinical development [ ] . (-f)-calanolide a ( ) i s a c coumari n isolate d fro m th e malaysia n rainfores t tree , calophyllum langigerum b y th e u.s . national cance r institut e [ ] . i t shows a poten t hiv-r t inhibitor y activit y [ ] . in vitro studie s o f demonstrated activit y agains t hiv- includin g az t an d othe r nonnucleoside r t inhibitors-resistan t strains . it als o show s synergisti c anti -hiv activity i n combination with nucleoside rt inhibitors: , and [ ] . to overcom e th e difficult y o f suppl y o f , its tota l chemica l synthesi s was accomplishe d [ ] . i n jun e , clinica l developmen t o f wa s started as a potential drug for treatment of aids. a single -center -mont h u.s. phas e l a clinica l tria l o f wa s starte d t o asses s it s safet y an d tolerability [ ] , sp- ( ) i s a mixtur e o f natura l oligomeri c proanthocyanidins u p to a molecular weigh t daltons. it is isolated from th e late x o f a latin america n plan t croton lechleri [ ] , it show s potent in vitro activity against hsv and other varieties of dna and rna viruses. virend, whic h i s the topical formulatio n o f , is evaluated i n phase ii clinical trials for the treatment of genital herpes in combination with acyclovir. these trials were later suspended as they proved virend to have no additional benefit over using oral acyclovir alone. provir, the oral formulation o f sf-sob, is proved to be safe and well tolerated in phase i trials but ineffective i n phase ii for the treatment of rsv since there was no adequate absorption by patients. however, provir was proved effectiv e in symptomati c treatmen t o f traveler' s diarrhe a throug h restoratio n o f normal bowel function and prevention of recurrences [ ] . alkaloids are heterogeneous group of compounds linked by the common possession o f a basi c nature , containin g on e o r mor e nitroge n atom s usually in combinations part of heterocyclic system [ ] , their precursors are usually amino acids and they exert certain biological activities. many alkaloids are also foun d i n animals and humans where they coul d exer t a profound pharmacologica l activit y [ ] . tabl e illustrate s variou s alkaloids with activity against many animal viruses. lycorine ( ), pretazettine ( ) apqrphing; oliverine ( ), pgnzqphgnanthriding: chelidonine ( ) schumannificine ( ) flavqiioid: opium; morphine ( ) , codeine ( ), papaverine ( ) phenantl iroquinozolizidine: cryptopleurine ( ) pipgriding; -deoxynojirimycin ( ) , l -deoxymannojirimycin ( ) , a-homonojirimycin ( ) protoberberine: berberine ( ) , columbamin e ( ) , palmatine ( ) pvrrolizidine: austra l ine ( ) ouinoline/isoquinoline: table summarizes the antiviral activity of plant and some non-plant carbohydrates. chromones, furanocoumarins an d flavonoids ar e common constituent s i n many plan t families . coumarin s ar e specifically abundan t i n the familie s rutaceae an d umbellifera e [ ] . the yield coul d sometime s reac h u p t o % o f the dr y plant weight . tabl e illustrates various antivira l activitie s of chromones, coumarins and flavonoids. lignans ar e widesprea d secondar y metabolite s i n plant kingdom . the y occur in many parts of plants especially wood, resin and bark trees [ ] . they are also found i n many roots, leaves, flowers, fruits an d seeds [ ] . there is an evidence that lignans play a major rol e in plant-plant, plantinsect an d plant-fungu s interaction s [ ] . the chemica l structure s o f t e r m i l i g n a n ( ) , t h a n n i l i g n a n ( ) , anolignan ( ) justicidin a ( ) [ ] lignans ar e divers e an d comple x despit e the y ar e essentiall y dimer s o f phenylpropanoid unit s (c -c ) linked by the central carbons of their sid e chains [ ] . presently, there are six lignan subgroups : butane derivatives , lignanolicles (butanolides) , monoepoxylignan s (tetrahydrofura n derivatives), bisepoxylignans ( , -dioxabicyclo( . . )-octane derivatives) , cyclolignans (tetrahydronaphthalenes ) an d cyclolignan s base d o n naphthalene [ ] . phenolics, benzoquinones , naphthoquinones , anthraquinones and phenylpropanoids ar e abundant secondary metabolite s in plants. table illustrates the reported antivira l activitie s of these plan t secondary metabolites. tannins ar e phenoli c compound s tha t ar e abundan t i n plan t kingdom . basically, ther e ar e tw o type s o f tannins . hydrolysabl e typ e whic h usually consists of simple phenolic acids, e.g., gallic acid, which is linked to sugar . th e condense d typ e i s simila r t o flavonoids . th e know n medicinal tannin-containin g plan t lemo n bal m (melissa officinalis, labiatae) is extensively studied as antiviral agent [ ] . leave s of this plant contain abou t % , dry weight o f tannins which ar e mainly constructe d from caffei c acid . a cream containing % of a specially prepare d dried extract from lemon balm leaves has been introduced to the german market for loca l therap y o f herpes infection o f the ski n [ ] . the effect o f this cream i n th e topica l treatmen t i s statisticall y significan t a s proven b y clinical studies [ ] . this is a decisive indication that constituents and /or extracts of plants could serve as useful lead s for developing the antiviral drugs for the future. terpenoids are also abundant secondary metabolites condensed tannins: catgghinjg aci d ( ) condense d t a n n i n s , p a v e t a n n i n s , cinnamtannins. galloy l catechi n an d epicatechin . procyanidin b ( ), [ ] in plant world. terpenoids are essentially derived from the basic -carbons isoprene unit . thes e ar e classifie d into : monoterpene s (cio) , sesquiterpenes (ci ) , diterpene s (c ) , triterpenes , sterols , saponins . about seve n hundre d polyacetylene s hav e bee n isolate d s o fa r mainl y from plant s belongin g t o th e famil y o f asteraceae , umbellifera e an d campanulaceae [ ] . polyacetylenes occu r principally a s straight chai n polyines, allenes , phenyl, thiophenyl , thioether an d spiroketal-enoethe r derivatives in a quite high yield. thiophenes and related sulfur compounds are usuall y groupe d togethe r wit h th e polyacetylene s becaus e o f thei r common biosyntheti c pathway s [ ] . few plant-derive d lactones , butenolides an d phospholipid s sho w antivira l activity . th e antivira l activities o f thiophenes , polyacetylenes , lactones , butenolide s an d phospholipids from plant origin are reported in table . thiarubine a ( ) thiophene-a ( ) phenylheptatriyne ( [ ] . additional proteins (pap-ii an d paps) were found i n relative smaller amounts. subsequently, other rips were found i n other plants and exhibit similar antiviral activity, e.g., tritin fro m triticum aestivum seed , geloni n fro m gelonium multiflorum seed , momordin fro m momordica charantia seed , sapori n fro m saponaria officinalis seed , dianthin fro m dianthus caryophyllus leaf , tricosanthi n from trichosanthes kirilowii [ ] , bryodin from bryonia dioica [ ] and bougainvillea antivira l protei n i (ba p i ) fro m bougainvillea spectabilis roo t [ ] . some varieties of nicotiana glutinosa produce a protein called avf which afford som e protectio n agains t tm v b y restrictin g it s lesion s i n a n analogy manne r t o interferon s [ ] . av f i s a glycoprotei n whic h i s terminally phosphorylate d wit h , dalton s molecula r weight . th e mechanism of action of avf is not yet established. meliacin i s a n antivira l glycopeptid e o f molecula r weigh t - daltons, isolated from th e leaves of melia azedarach (meliacea ) [ , ] . its aprotinine i s anothe r plant-derive d antivira l polypeptid e whic h specifically inhibi t myxoviruse s especiall y influenz a a . aportinin e i s known to be a protease inhibitor . it acts by interferin g wit h the essentia l step of cleavage of the precursor hao into subunit polypeptides and hence prevents the viral infection [ ] . many plant-derive d di -and tri-peptides wer e proved to be active agains t hsv an d measle s viru s (mv) . thes e peptide s consis t mainl y o f carbobenzoxy derivative s o f phenylalanin e [ ] . cationi c peptide s ar e used as nature's antibiotics, being produced i n response to an infection i n virtually mos t organism s includin g plant s an d insects . cationi c peptide s and protein s ar e no w proceedin g throug h clinica l trial s a s topica l antibiotics and antiendotoxins [ ] . several thousan d plan t extract s hav e bee n show n t o posses s in vitro antiviral activit y wit h littl e overla p i n specie s betwee n studies . i n mos t cases, th e assa y method s ar e designe d t o detec t virucidal , prophylacti c [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] activities an d t o defin e extract s tha t interfer e w^it h vira l replicatio n i n cultured cells . aqueous an d organi c extract s have generall y bee n prove d equally fruitfu l an d hence i t is not feasible t o asser t that an y on e metho d of extractio n i s preferable . furthe r characterizatio n o f th e activ e constituents in these active extracts should reveal some useful compounds . many o f activ e extract s ma y tur n ou t t o b e identica l o r relate d t o th e previously describe d structure classes. yet, there also may be a possibility for som e nove l phytochemicals . tabl e summarize s som e o f th e mos t active extracts in the literature. with marin e specie s comprisin g approximatel y on e hal f o f tota l globa l biodiversity fo r whic h estimate s rang e betwee n - x ^ specie s o f prokaryote and eukaryote organisms. the marine macrofauna represent s a broader rang e of taxonomic diversit y than found i n terrestrial evironmen t [ ] . with a typical eukaryote possessing , genes, the global marine macrofauna ar e the source of . x ^^ - . x ^ primary products an d an associate d extensiv e rang e o f secondar y metabolite s [ ] . presently, only fe w thousan d nove l compound s fro m marin e origi n hav e bee n identified. thes e compounds have been revealed unique in chemical and pharmacological terms . however, onl y fe w promising therapeuti c lead s many marine-derived peptides, alkaloids, proteins, nucleosides and other a^-containing compound s were show n to be active agains t severa l vira l species. table illustrates these activities. the antiviral activities of various marine-derived terpenoids, steroids and carotenoids are summarized in table . halogenated cyclohexadienone ( ) sggqviitgrpgngs: avarol ( ) [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ( table ) . contd.. [ ] . a polysaccharide from the green marine alga ulva lactuca inhibited the reproduction of many human and avian influenza viruses . acid hydrolysi s of thi s polysaccharid e reveale d th e presenc e o f arabinose , xylose , rhamnose, galactose , mannos e an d glucos e i n rati o o f : : : : : : , respectively along with an unidentified suga r [ ] . treatment o f laminari n isolate d fro m th e marin e alg a laminaria cichorioides b y endo-p-l, -glucanas e fro m marin e invertebrate s transformed p-l, :l, -gluca n int o a highl y efficien t preparatio n agains t tobacco mosai c virus named antivi r [ ] . polysaccharides, compose d o f mannose, galactose, glucose, uronic acid and sulfate group s ( - % wt/wt) was obtained from the marine microalga cochlodinium polykrikoides sho w potent inhibitor y activitie s against : influenz a viruse s typ e a an d b , respiratory syncytia l viruse s typ e a an d b , hiv- , hsv- an d parainfluenza viruse s typ e and . no cytotoxicit y no r inhibitio n t o th e blood coagulation were observed up to |lig/ml [ ] . an unusua l sulfate d mannos e homopolysaccharide , isolate d fro m th e pacific tunicat e didemnum molle show s in vitro anti-hi v activity . th e nmr dat a of this polysaccharide reveal s that it consists o f a sequence o f , -disulfated mannos e unit s joined throug h p ( , ) glycosidi c linkage s [ ] . a natural sulfate d mucopolysaccharid e (oku ) , extracted fro m a marine plan t dinoflagellata an d a n artificia l sulfate d polysaccharid e ( ku ), was prepared fro m a marine pseudomonas, displaye d antivira l activities agains t hiv- an d - , zidovudine-resistan t hiv- , hsv- , influenza viruse s a an d b , respiratory syncytia l viru s an d measle s viru s without displayin g cytotoxicit y o r inhibition o f blood coagulatio n o f host cells [ ] . table illustrates the reported antiviral activities of the common marin e secondary metabolite s polyacetylenes , quinones/pyrones , macrolide s an d prostaglandins. the human dream of finding a n antiviral antibiotic from microbial origin which selectively affects the viral but not the host cell in a similar manner to th e regula r antibiotic s ha s no t becom e a reality . however , severa l microbial-derived metabolite s sho w promisin g activity . th e us e o f microbes t o modif y syntheti c compound s o r t o accomplis h specifi c desired reactio n i s commo n i n pharmaceutica l industry . adenin e arabinoside (ara a, ) , which is approved for clinical investigation, is also produce d b y a streptomyces s p [ ] . example s o f secondar y metabolites fro m microbia l origi n tha t sho w antivira l activitie s ar e presented below. rifamycins ar e microbial-derived macrolide s that were isolated i n from the actinomycete streptomyces mediterranei, obtained from the soil of the pine forests of southern france [ ] . of these, rifamycin b ( ) is the leas t toxic . additio n o f diethylbarbituri c aci d t o th e fermentatio n medium result s i n th e productio n o f only . rifampici n i s th e c hydazone semisyntheti c derivativ e o f rifamycins . rifamycin s sho w in vitro and in vivo anti-poxyviruses, e.g., vv activities [ ] . these activities are apparently du e to inhibition of the early step of viral morphogenesi s which affect s th e assembl y o f immatur e vira l particles . the inhibitor y activity of rifamycins o n retroviruses is also reported [ ] . many natural and semisyntheti c rifamycin s inhibi t th e virio n rna-dependen t dn a polymerase (rt ) [ ] . rifamycin b ( ) wa s reported activ e agains t murine sarcom a viru s (msv ) du e t o it s rt , focu s formatio n an d cel l transformation inhibitor y activities [ ] . rifamycin antibiotics also inhibit the rt of rauuscher leukemia virus, preventing its leukomogenic activity [ ] . streptovaricin b ( ), tolypomycin an d geldanamycin ar e examples of ansamycins whic h ar e chemicall y relate d t o rifamycins . th e streptovaricins an d tolypomycin s resembl e rifamycins i n rt-inhibitor y activity [ ] . streptovaricin b inhibits the replication o f poxviruses by inhibiting earl y stage s o f mrn a synthesi s [ ] . inhibitio n o f focu s formation of msv by streptovaricins is also reported [ ] . gliotoxin ( ) is a fungal metabolite , isolated from aspergillus terreus and foun d t o hav e antibacterial , antitumo r an d antifunga l effect s [ ] . gliotoxin acetate inhibited the cpe of poliovirus in monkey kidney cell cultures due to the early stag e inhibition o f rna viral replication [ ] . gliotoxin also inhibits influenza virus-induced rna polymerase. arantonins are related compounds, isolated from arachniotus aureus dixidi aspergillus terreus and show rt inhibitory activity [ ] . the activity is attributed to the epidithiapiperazinedione moiety, as the case of . sporidesmin distamycin a ( ) i s a n oligopeptide , isolate d fro m streptomyces distallicus that inhibits transcription and replication of dna viruses along with its other related semisynthetic analogs [ ] . example of dna viruses inhibited by this group are vaccinia virus and hsv- . distamycin a also shows inhibitory activity for rt of retroviruses [ ] . daunomycin ( ) and doxorubicin ( ) are anthracycline glycosides , isolated from streptomyces peucetius [ ] . these compounds are used in cancer chemotherapy du e to their ability to bind dna. both compounds inhibit rt and production of murine leukemia virus [ ] . actinomycin d is a peptide antibiotic, produced by streptomyces parvulu. it interacts with cellular dna and inhibits the replication of mammalian viruses tha t depen d o n cellula r functions , e.g. , rabie s viru s [ ] . mithramycin i s a relate d compoun d tha t inhibit s influenz a an d pseudorabies viruse s probabl y du e t o inhibitio n o f hos t cel l rn a polymerase ii [ ] . cordyceptin ( ) i s a fermentation produc t o f th e fung i aspergillus nidulans and cordyceps militaris. cordyceptin inhibit s the synthesis of mrna an d hence the replication o f both rna an d dna viruses [ ] . [ ] . toyocamycin ( ) i s anothe r adenosin e derivativ e produce d b y streptomyces toyocaensis [ ] . this compoun d selectivel y inhibit s th e ribosomal rn a synthesi s i n fibroblasts . th e synthesi s o f adenovirusspecific mrn a is also inhibited by [ ] . sinefungin i s a n adenin e derivative , isolate d fro m streptomyces griseolus an d i t effectivel y inhibit s v v mrn a (guanine- -jmethyltransferase an d hence inhibits methylation of its mrn a [ ] . bilayer structure . filipin show s activity agains t vsv and to less degree against influenza and rauscher leukemia virions [ ] . amphotericin b is another related antifungal antibiotic. its methyl ester is active against hsv- and - , vv, sv and vsv with less cytotoxicity and improved water solubility [ ] . aphidicolin i s a tetracycli c diterpenoid , produce d b y th e fungu s cephalosporium aphilicola. it has the ability to inhibit hsv- , - , vv and herpetic keratitis of rabbit [ ] . the mechanism of this compound is not yet established. cytochalasin b ( ) i s a metabolite o f the mol d helminthosporium dermatoideum [ ] . it inhibits hexose transport i n cells and hence i t is used fo r th e stud y o f virus-specifi c glycoprotei n synthesis . i t show s potent inhibitor y activit y agains t hsv- an d - apparentl y du e t o th e inhibition of viral glycosylation [ ] . cytochalasin d is a closely related compound tha t show s activit y agains t adenoviru s bu t i t enhance s th e infectivity of poliovirus and parainfluenza [ ] . it is a phenolic acid, isolated from a penicillium sp. and shows inhibitory activity against hsv- and - , vv, semliki forest, influenza a viruses and coxsackievirus. its effect i s probably due to cytotoxicity [ ] . additional antivira l microbial-derived metabolite s are summarized i n table . there i s a n urgen t nee d t o identif y nove l activ e chemotype s a s lea d fo r effective antivira l chemotherapy . recen t year s hav e witnesse d grea t advances in this area. the enormity of natural products as antiviral agent s started t o b e expresse d i n th e are a o f antivira l chemotherapy . thi s i s represented b y the fda's approva l fo r clinica l investigatio n o f two plantderived compounds, in addition to one compound of marine origin and one microbial-derived compound . ou t o f te n syntheti c approve d drug s between - , seve n wer e modeled o n a natural produc t pare n [ ] . the developmen t o f recen t technique s t o dereplicate , accuratel y detect , isolate, structurall y defin e an d automate d assa y th e bioactiv e natura l products will result in more lead of antiviral agents. it has been estimate d that onl y - % o f th e approximatel y , specie s o f highe r plant s have bee n systematicall y investigate d fo r th e presenc e o f bioactiv e compounds while the potential of the marine environment has barely bee n tapped [ ] . consequently , natura l product s represen t potentia l antivira l leading resources for imaginative discoverers. natural product s a s a resource fo r new drugs recent natural products based drug development: a pharamaceutical industry perspective plant products as potential antiviral agents natural products in drug discovery and development the virus a history of the concept virology apoptosis i n viral infections. i n apoptosis: the molecular basis of cell death marburg an d ebol a viruses . i n antivira l compound s fro m plants plan t substance s a s antiviral agents basi c & clinica l pharmacology antiviral agents : characteristic activit y spectru m dependin g o n the molecula r targe t wit h whic h the y interact interferon-induce d antivira l action s an d thei r regulation. i n va n hoof , l . plan t substance s a s antiviral agents biorgani c marin e chemistry antivira l agent s fro m natura l sources chemotherapy o f viral infection . natura l products natura l product s a s antivira l agents anti-huma n immunodeficienc y virus (anti-hiv ) natura l product s wit h specia l emphasi s o n hi v revers e transcriptase inhibitors antivira l substances screening o f highe r plant s fo r plant antivira l agents . iii. isolation o f alkaloid s from clivia miniata rege l (amaryllidaceae) antiherpe s viru s activit y o f aporphine alkaloids biologica l an d phytochemical evaluatio n o f plants . v . isolatio n o f tw o cytotoxi c alkaloid s from chelidonium majus effect o f benzo[c]phenanthidin e alkaloids on reverse transcriptase and their binding property to nucleic acids evaluatio n o f natura l product s a s inhibitors o f huma n immunodeficienc y viru s type- (hiv- ) revers e transcriptase anti-hi v an d cytotoxic alkaloid s fro m buchenavia capitata antivira l component s of ophiorrhiza mungo tetrahydroxyoctahydroindolizidine alkaloid , fro m seed s o f castanospermum anstrale castanospermin e i n alexia species inhibitio n o f mammalian digestiv e disaccharide s b y polyhydrox y alkaloids anti-hi v michellamine s fro m ancistrocladus korupensis michellamin e b , a novel plan t alkaloid, inhibit s huma n immunodeficienc y virus-induce d cel l killin g b y a t least two distinct mechanisms a n activ e antiviral alkaloi d fro m boehmeria cylinderica (l. ) sw . (urticaceae) a-homono-jirimycin [ , -dideoxy- , -imino-dglycerol-l-heptitol ] fro m omphalea diandra l. : isolatio n an d glucosidas e inhibition enzym e inhibition . viii : mod e o f inhibitio n o f revers e transcriptaseactivity b y analogues, isomers and related alkaloids o f coralyne inhibitor y natural products . . quinolin e alkaloid s fro m euodia oxburghiana antiherpes viru s actio n o f atropine activit y i n vitro of mgn- , an activated arabinoxyla n from ric e bran myeloblastosi s an d huma n immunodeficiency viru s revers e transcriptas e inhibitors , sulfate d polysaccharides extracte d fro m se a algae antimicrob glycoprotein of human immunodeficiency typ e bind s sulfated polysaccharide s and cd -derived syntheti c peptides reverse transcriptas e isolate d fro m th e malaysia n tree , callophyllum inophyllum linn e. a-(l- )-d-mannose-specifi c plan t lectins are markedly inhibitor y to human immunodeficiency viru s an d cytomegaloviru s infection s in vitro anti-huma n immunodeficiency viru s phenolic s from licorice the calanolides , a novel hiv-inhibitor y clas s o f coumari n derivative s fro m the tropical rainfores t tre e callophyllum langigerum specifi c inhibitio n o f th e revers e transcriptas e o f huma n immunodeficiency viru s typ e an d th e chimeri c enzyme s o f huma n immunodeficiency viru s typ e an d b y non -nucleosid e inhibitors specifi c inhibition o f huma n immunodeficienc y viru s typ e reverse transcriptas e mediated by soulattrolide, a coumarin isolate d from the latex of calophyllum teysmannii studie s of the plantaginis herba. . inhibitory effects o f flavonoids from plantago specie s on hiv reverese transcriptase activity thre e dimensiona l quantitativ e structure-activit y relationshi p (qsar) o f hi v integras e inhibitors : a comparativ e molecula r fiel d analysi s activit y o f som e flavonoids agains t viruses antivira l activit y o f flavone s an d flavans antiviral activit y o f -methoxyflavones , i n "plan t flavonoid s i n biolog y an d medicine: biochemical , pharmacologica l an d structure-activit y relationships " cody ne w antivira l compound s i n "advances i n viru s research antivira l avtivit y o f , , -. chemother, trimethoxyflavon e an d its potentiation o f the antiherpes activit y o f acyclovir differentia l inhibitory effect s o f variou s her b extract s o n th e activitie s o f revers e transcriptase an d variou s deoxyribonuclei c aci d (dna ) polymerase isolation an d structur e o f woodorien , a ne w glucosid e havin g antivira l activity fro m woodwardia orientalis mechanisti c evaluatio n o f ne w plant-derive d compounds tha t inhibi t hiv -revers e transcriptase biologica l activitie s o f lignans secondar y metabolite s fro m plant s a s antiretroviral agents : promisin g lead structure s fo r anti-hi v drug s o f th e future a n investigatio n o f th e antivira l activit y o f podophyllum peltatum studie s o n th e pharmacologica l activitiesof amazonian euphorbaceae assesmen t o f th e anti-hi v activit y o f a pin e cone isolate nove l i n vitr o anti-hi v activ e agents arctigeni n a s a lea d structur e fo r inhibitor s o f huma n immunodeficiency viru s type- integrase tw o ne w lignan s with activit y agains t infuenz a viru s fro m th e medicina l plan t rhinacanthus nasutus new anti-hiv , antimalarial an d antifungal compound s from terminalia bellerica antivira l activit y o f lignan s an d their glycosides from justiciaprocumbens selective inhibition o f human immunodeficienc y virus type- synthesis and anti-hiv activit y o f l,r-dideoxy-gossypo l and related compounds vergleic h de r antivirale n aktivita t vo n oxidierte r kaffiisaure un d hydrokaffeesaure gege n herpesvirus hominis typ i und typ in vitro antiviral caffeoy l ester s fro m spondias mombin anti-aid s agents , . isolatio n an d characterization o f fou r new tetragalloylquini c acid s a s a new clas s o f hi v reverse transcriptas e inhibitor s fro m tanni c acid anti -aids agents, . inhibitory effect s o f tannins on hiv reverse transcriptase an d hiv replication i n h lymphocyte cells th e peltatols , nove l hiv-inhibitor y catecho l derivative s from pothomorphe peltata nove l phloroglucinol s fro m th e plan t melicope sessiliflora (rutaceae) cytotoxi c an d antiherpetic activit y o f phloroglucino l derivative s fro m mallotus japonicus (euphorbiaceae) structur e o f euglobal-gl , -g an d -g fro m eucalyptus gerandis. thre e new inhibitor s of epstein-barr virus activation structur e o f syzygiol : a skin-tumo r promotio n inhibitor hiv-revers e transcriptas e inhibitor s o f eucalyptus globulus hiv-inhibitor y an d cytotoxic oligostilbenes fro m th e leaves of hopea malibato inactivation o f envelope d viruse s b y anthraquinone s extracte d fro m plants anthraquinone s a s a new clas s o f antivira l agents agains t huma n immunodeficienc y virus light-induce d acidificatio n b y the antiviral agen t hypericin a poten t nove l hiv-inhibitor y naphthoquinon e trime r from a concospermum sp antivira l phenylpropanoi d glycoside s from th e medicinal plan t markhamia lutea secondar y metabolite s from plant s a s antiretroviral agents : promisin g lead structure for anti-hlv drugs of the future purification an d characterization o f antiviral substance s from th e bud of syzygium aromatica antiviral substance s from the root of paeonia species euagitannin s a s activ e constituent s o f medicinal plants structure an d antiherpetic activit y amon g th e tannins antiviral euagitannin s fro m spondias mombin phytochemistry inhibitor y effect s o f tannin s o n revers e transcriptas e fro m rn a tumo r virus anti-hiv activit y o f euagitannins comparativ e studies of the inhibitory propertie s of antibiotics o n human immunodeficienc y virus and avaian myeloblastosi s virus reverse transcriptas e an d cellular dn a polymerase viru s inhibitio n b y tea , caffein e an d tanni c acid plant antivira l agents . vii. antiviral an d antibacterial proanthocyanidin s fro m the bark of pavetta owariensis a-typ e proanthocyanidin s fro m ste m bar k o f pavetta owariensis dimeri c an d trimeri c proanthocyanidin s possessin g a doubl y linke d structur e fro m pavetta owariensis antivira l activit y o f tanni n fro m th e pericarp of punica granatum l . against genital herpes virus in vitro effects o f condensed tannin s and related compounds on reverse transcriptase inhibitory effects o f tannic acid sulfate an d related sulfate s o n infectivity, cytopathi c effec t an d gian t cel l formatio n o f huma n immunodeficiency vms in vitro antiviral activity o f calcium elenolate antivira l agents o f plant origin . ii . antiviral activit y o f scopaduli c aci d b derivatives th e effec t o f a^-tetrahydrocannabino l o n hepes simplex viru s replication antiviral agent s o f plant origin . iii . scopadulin , a nove l tetracycli c diterpen e fro m scoparia dulcis inactivation o f measel s viru s an d herpes simplex viru s b y saiko-saponins structur e o f tw o antivira l triterpen e saponin s fro m anagallis arvensis in vitro activity of dammar resi n triterpenoid effect o f saponins from anagallis arvensis on experimenta l herpes simplex keratiti s i n rabbits preliminar y studie s o f antivira l activit y o f triterpenoi d saponins : relationships betwee n thei r chemical structure s an d antiviral activity antivira l activitie s o f glycerrhizin an d it s modifie d compound s agains t huma n immunodeficienc y virus typ e (hiv- ) an d herpes simplex typ e (hsv- ) in vitro cytotoxi c saponin s fro m ne w zealan d myrsine specie s triterpenoi d saponin s fro m maesa lanceolata triterpenoid saponin s a s anti-hi v principle s from fruit s o f gleditsia japonica an d gymnocladus chinensis an d a structur e activit y correlation anti-hi v triterpen e acid s from geum japonicum betulinic aci d an d platani c aci d a s anti-hi v principle s from syzigum claviflorum an d the anti-hiv activit y o f structurall y relate d triterpenoids betulini c aci d derivatives : a ne w class of human immunodeficienc y viru s type specific inhibitor s with a new mode of action betulinic aci d derivatives : a ne w clas s o f specifi c inhibitor s o f huma n immunodeficiency viru s type entry antivira l activit y o f dammarane saponin s agains t herpes simplex viru s i anti-aids agents. . anti-hiv activit y o f oleanoli c acid, pomoli c aci d an d structurall y relate d triterpenoids nigranoi c acid , a triterpenoid fro m schisandra sphaerandra tha t inhibit s hiv- revers e transcriptase alkylidene bicyclic butenolide with antiviral activity and its p-glucopyranosid e from homalium cochinchinensis molecular similarit y o f anti-hi v phospholipids bryodi n a ribosome-inactivatin g protein fro m th e plan t bryonia dioica, , us patent a n antivira l protei n from bougainvillea spectabilis roots ; purificatio n an d characterization protei n toxin s an d thei r us e i n cel l biology expression characteristic s o f pokeweed antivira l proteins (paps) : two distinct type s of proteins action s o f pokewee d antiviral protei n o n virus-infecte d protoplasts plan t immunomo-dulator s fo r terminatio n o f unwante d pregnanc y an d fo r contraception an d reproductive health inhibitio n o f foo t an d mout h viru s (fmdv) uncoating by a plant-derived peptid e isolate d from melia azedarach l . leaves. argent th e therapeuti c potentia l o f cationic peptides nee m see d oi l inhibit s aphi d transmission o f potat o viru s y t o pepper antiinfectiv e activit y o f a plan t preparatio n from geranium sanguineum l in vitro anti-influenz a viru s activit y o f a plan t preparation fro m geranium sanguineum l phyllanthus amarus suppresse s hepatiti s b viru s b y interruptin g interactio n betwee n hb v enhance r i an d cellula r transcription factors th e plant s of th e genu s phyllanthus a s a potentia l sourc e o f new drugs a revie w of th e plant s o f th e genu s phyllanthus: thei r chemistry , pharmacolog y an d therapeutic potential nontoxi c therapeuti c extract s o f larrea tridentata in vitro activity o f extracts of persea americana leave s on acyclovir-resistan t an d phosphonoaceti c resistan t herpes simplex virus antiviral activit y o f a n extrac t fro m leave s o f th e tropica l plan t acanthospermum hispidum interaction b y various plant extracts anti-herpeti c activit y o f variou s medicina l plan t extracts stud y o f stapelia pregnane s an d veratrum alkaloids anti-hi v activit y o f alkalin e extract s o f rooibo s te a leaves progres s i n th e acquisitio n o f ne w marine -derived anticance r compounds : developmen t o f ecteinascidin- (et- ) pharmacologicall y activ e compound s fro m marin e invertebrates: drugs from the sea marin e product s a s a sourc e o f antivira l dru g leads . drug development research antiviral an d antitumor compound s fro m tunicates structure s of th e didemnins , antivira l an d antitumo r depsipeptide s fro m a caribbea n tunicate antivira l an d antitumo r compound s fro m a caribbea n tunicate bioactiv e peptides from a marine mollus k elysia rufescens an d its algal diet bryopsis sp callipeltin a , an anti-hiv cycli c depsipeptid e from th e new caledonia n lithistid a spong e callipelta sp eudistomin s c ; e ; k an d l ; poten t antivira l compound s containing nove l oxathiazepin e rin g fro m caribbea n tunicat e eudistoma olivaceum bromotopsenti n an d dihydroxybromotopsentin: antivira l and antitumor bis(indolyl) imidazoles from caribbean deep-se a sponge s o f th e famil y halichon d fro m a sponge dercitus sp a ne w guanidinostyren e fro m th e cora l tubastrea aurea nove l antivira l an d antimicrobia l compounds from th e spong e acarnus erithacus (d e laubenfles) revised structure s of polyandrocarpidines antivira l an d antibacteria l bromopyrrol s from agelas coniferin and hal o derivative s thereof bioactiv e compounds from aquati c an d terrestria l sources mycalamid e a , a n antiviral compoun d from a new zealan d spong e o f th e genu s mycale antivira l an d antitumor agent s from a ne w zealan d sponge , mycale sp . . structure s an d solution conformation s o f mycalamides a and b isolatio n an d structur e elucidation of onnamide a, a new metabolite of a marine sponge, theonella sp ptilomycalin a : a novel polycyclic guanidine alkaloid o f marine origin new antiviral an d cytotoxic compound s fro m th e spong e cramb e crambe bioactiv e bisoxazole s from a marine sponge antiviral indolocarbazole s from a blue-green alg a belongin g t o th e nostocaceae aplidiasphingosine , a n antimicrobia l an d antitumo r terpenoid from a n aplidiiim sp . (marine tunicate) nove l alkaloid s fro m th e spong e batzella sp. : inhibitors o f hiv gpl -human cd binding b-carboline s fro m th e blue-gree n alga dichothrix baueriana alkaloid s fro m antarcti c spong e kirkpatrickia varialosa. par t : variolin b , a new antitumo r an d antivira l compound unusua l re d pigmen t fro m th e spong e trikentrion loeve, anti-hiv- metabolite contributio n t o th e stud y o f marin e products . xxxii. the nucleosides o f sponges antivira l agent s from a gorgonian a proto n nuclea r magnetic resonance study of the antihypertensive and antiviral protein bds- from th e se a anemon e anemonia sulcata: sequentia l an d stereospecifi c resonance assignmen t and secondary structure -(l-chloro- -hydroxyethyl)- , -dimethylcyclohexa- , -dienone : a precursor of , -dimethylbenzo[i]furan from the red alga desmia hornemanni inhibitio n o f the replicatio n of etiologi c agen t o f acquire d immun e deficienc y syndrom e (huma n t -lymphotropic retroviru s /lymphadenopathy-associate d virus ) b y avaro l an d avarone antivira l chamigren e derivative , pc t internationa l application w o sesquiterpenoid isocyanid e purificatio n from a marine sponge an d its use as a neoplasm inhibitor , virucide and fungicide a n antivira l sesquiterpen e hydroquinone from the marine sponge strongylophora hartmani thre e new sesquiterpen e hydroquin-ones from marine origin frondosin s a an d d , hiv -inhibitory sesquiterpen e hydroquinon e derivative s from euryspongia sp cytotoxic and antiviral diterpene from a caribbean deep water marine sponge, spongia sp ne w antiinflammator y an d antiviral diterpenoid s fro m a marine octocoral o f the genus solenopodium brianthei n v , a new cytotoxic an d antiviral diterpen e isolate d from briareum asbestinum reiswigin s a an d b , nove l antiviral diterpene s fro m a dee p wate r sponge bioactive norsesterterpene , -dioxane s froma thia sponge , mycale sp variabilin an d relate d compounds from a sponge genus sarcotragus venustatriol : a ne w antiviral triterpene tetracycli c ether from laurencia venusta holothurinosides : ne w antitumo r no n sulphated triterpenoi d glycoside s from the sea cucumber holothuriaforskalii biologically activ e saponin s an d saponin-lik e compound s fro m starfis h an d brittle-stars new secosteroids from an undescribed gorgonia n o f the genu s muricella hiv-inhibitor y natura l products . . comparative studie s of sulfated sterol s from marine invertebrates weinbersterol disulfate s a and b , antivira l steroi d sulfate s fro m th e spong e petrosia weinbergi new antivira l stero l disulfat e ortho esters fro m th e marin e spong e petrosia weinbergi meroterpene s fro m cystoseira usneoides ii cucumaria-xanthin s a , b and c from the se a cucumber cucumaria japonica caracterisation chimiqu e e t activit e virostatiqu e in vitro vis d u viru s d e la fevere jaune quelques carraghenanes extrait s d'algues roug e senegalaises polysaccharides a s antivira l agents : antiviral activit y o f carrageenan antivira l carbohydrate s from marin e re d algae antiviral and anticoagulant activity of polysaccharides from marine brown algae antivira l activitie s o f sulfate d derivative s o f a fucosamine -containing polysaccharide o f marine bacterial origin inhibitor y effec t o f sulfate d derivative protectio n o f tobacc o plant s against tobacc o mosai c viru s b y b-l, ;l, -gluca n "antivir " obtaine d b y enzymatic transformatio n o f laminarin in vitro antiviral activitie s o f sulfated polysaccharide s fro m a marine microalga {cochlodinium polykrikoides) against huma n immunodeficienc y viru s an d othe r envelope d viruses a sulfate d mannose polysaccharid e wit h anti-hi v activit y fro m th e pacifi c tunicat e didemnum molle brominate d polyacetyleni c avid s fro m th e marin e spong e xestospongia muta: inhibitor s of hiv protease petrosynol an d petrosoli c acid, tw o nove l natura l inhibitor s o f th e revers e transcriptas e o f huma n immunodeficiency viru s from petrosia sp absolute stereo -chemistr y o f onchitriol s i and ii mod e o f inhibitio n o f hi v revers e transcriptase b y -hexaprenylhydroquinone, a novel genera l inhibito r of rnaand dna-directed dna polymerases antibioti c an d antitumo r misakinolid e composition an d thei r derivatives . pc t internationa l applicatio n w o a ne w inhibito r o f huma n cytomegaloviru s proteas e fro m streptomyces sp a nove l antivira l agents whic h inhibit s th e endouncleas e o f influenz a viruses sattabacin s an d sattazolins : new biologicall y activ e compound s with antivira l propertie s extracte d from a bacillus sp ne w antivira l antibiotics , kistamicin s a an d b . i . taxonomy , production, isolation , physico -chemica l propertie s an d biological activities isolatio n an d synthesi s o f caprolactin s a and b , ne w caprolactam s from a marin e bacterium structures o f ne w polyacetylen e triglyceride s an d indolocarbazole s fro m th e myxomycetes lycogala epidendrum antibiotic s fro m glidin g bacteri a xlvii. thiangazole : a novel inhibito r o f hiv- fro m polyangium sp fluvirucin s al , a , bl , b , b , b an d b , ne w antibiotics activ e agains t influenz a a virus. i. production, isolation , chemica l properties an d biological activities structura l studie s o f mm , a nove l tetroni c acid containin g macrolid e wit h antivira l an d antibacteria l activit y isolate d from actinomadur a pelletieri antibiotic s fro m glidin g bacteria . xliii . phenoxan : a nove l inhibitor o f hiv- infectio n i n cel l culture s from polygoniu m sp. , strai n p i v (myxobacteria) structur e an d biologica l activity a new peptid e antibiotic . production, isolation , an d propertie s o f lanthiopeptin manufactur e o f diaminobutyri c aci d homopolymer wit h streptoalloteichu s fo r us e a s antibioti c an d virucide derivatives of oxetanocin: oxetanocins h, x and g and -aminooxetanocin a a ne w adenosin e deaminase inhibitor containing chlorine. production, isolation and properties a novel specific inhibito r against reverse transcriptase structur e o f virantmycin , a nove l antivira l antibiotic studie s o n sf- c substance . meiji seika kenkyu nempo a new antiherpetic agent, ah- lia, produced by streptomyces cyaneus strai n no. structur e o f sc h : a new hepatiti s c virus proteinas e inhibito r fro m streptomyces sp pradimici n antibiotics an d thei r manufactur e wit h actinomadura new antivira l antibiotics , cycloviracins b l an d b . . production, isolation , physico-chemica l propertie s an d biologica l activities the structure s o f quartromicin s al , a an d a : novel macrocycli c antivira l antibiotics possessin g fou r tetroni c aci d moieties antibiotic s from basidiomycetes . xxxix. podoscyphic acid , a new inhibito r of avian myeloblastosi s viru s an d moloney murin e leukemi a viru s revers e transcriptas e fro m a podoscypha species key: cord- - f fep a authors: demain, arnold l. title: valuable secondary metabolites from fungi date: - - journal: biosynthesis and molecular genetics of fungal secondary metabolites doi: . / - - - - _ sha: doc_id: cord_uid: f fep a fungi are amazing producers of natural products, including secondary metabolites. these compounds are crucial to the health and well-being of people throughout the world. they also provide agriculture and livestock with many essential products. production of secondary metabolites is improved by mutagenesis and recombinant dna technologies allowing commercial production of these valuable compounds. this chapter centers on these fungal beneficial products, the discovery of which goes back years to the time that penicillin was discovered by alexander fleming. biosynthetic genes are present in clusters coding for large, multidomain, and multi-modular enzymes such as polyketide synthases, prenyltransferases, nonribosomal peptide synthases, and terpene cyclases. genes adjacent to the biosynthetic gene clusters encode regulatory proteins, oxidases, hydroxylases, and transporters. aspergilli usually contain - secondary metabolite gene clusters. strategies to activate silent genes have been reviewed by brakhage and schroekh [ ] . currently, with less than % of the microbial world having been cultured, there have been signifi cant advances in microbial techniques for growth of uncultured organisms as a potential source of new chemicals [ ] . furthermore, metagenomics-i.e., the extraction of dna from soil, plants, and marine habitats and its incorporation into known organisms-is allowing access to a vast untapped reservoir of genetic and metabolic diversity [ , ] . the potential for discovery of new secondary metabolites with benefi cial use for humans is great. a method to predict secondary metabolite gene clusters in fi lamentous fungi has recently been devised [ ] . microbes normally produce secondary metabolites in only tiny amounts due to the evolution of regulatory mechanisms that limit production to a low level. such a level is probably enough to allow the organism to compete with other organisms and/or coexist with other living species in nature. the industrial microbiologist, however, desires a strain that will overproduce the molecule of interest. development of higher-producing strains involves mutagenesis and, more recently, recombinant dna technologies [ ] . although some metabolites of interest can be made by plants or animals, or by chemical synthesis, the recombinant microbe is usually the "creature of choice." thousandfold increases in production of small molecules have been obtained by mutagenesis and/or genetic engineering. other important parts of industrial production include creating a proper nutritional environment for the organism to grow and produce its product, and the avoidance of negative effects such as inhibition and/or repression by carbon sources, nitrogen sources, phosphorus sources, metals, and the fi nal product itself. avoidance of enzyme decay is also desired [ , ] . over the years, the pharmaceutical industry extended their antibiotic screening programs to other areas [ , ] . since microorganisms are such a prolifi c source of structurally diverse bioactive metabolites, the industry extended their screening programs in order to look for microbes with activity in other disease areas. as a result of this move, some of the most important products of the pharmaceutical industry were obtained. for example, the immunosuppressants have revolutionized medicine by facilitating organ transplantation [ ] . other products include antitumor drugs, hypocholesterolemic drugs, enzyme inhibitors, gastrointestinal motor stimulator agents, ruminant growth stimulants, insecticides, herbicides, antiparasitics versus coccidia and helminths, and other pharmacological activities. catalyzed by the use of simple enzyme assays for screening prior to testing in intact animals or in the fi eld, further applications are emerging in various areas of pharmacology and agriculture. of the , antibiotics known in , fi lamentous fungi produced % [ , ] . the beta-lactams are the most important class of antibiotics in terms of use. they constitute a major part of the antibiotic market. included are the penicillins, cephalosporins, clavulanic acid, and the carbapenems. of these, fungi are responsible for production of penicillins and cephalosporins. the natural penicillin g and the biosynthetic penicillin v had a market of $ . billion by the late s. major markets also included semisynthetic penicillins and cephalosporins with a market of $ billion. in , the market for cephalosporins amounted to $ . billion and that for penicillins was $ . billion. by , production of all beta-lactams had reached over , t. the titer of penicillin is over g l − and that for cephalosporin c is about g l − [ , ] . recovery yields are more than %. there have been more than , molecules based on penicillin that have been made by semisynthesis or by total synthesis. by the mid s, antibiotics and their derivatives were already on the market [ , ] . the market in was $ billion. despite these impressive fi gures, more antibiotics are needed to combat evolving pathogens, naturally resistant microbes, and bacteria and fungi that have developed resistance to current antibiotics. a new and approved cephalosporin is ceftobiprole, which is active against methicillin-resistant s. aureus (mrsa) and is not hydrolyzed by a number of beta-lactamases from gram-positive bacteria [ ] . another antibiotic of note is cerulenin, an antifungal agent produced by acremonium caerelens . it was the fi rst inhibitor of fatty acid biosynthesis discovered [ ] . it alkylates and inactivates the active-site nucleophylic cysteine of the ketosynthase enzyme of fatty acid synthetase by epoxide ring opening. other properties that are desired in new antibiotics are improved pharmacological properties, ability to combat viruses and parasites, and improved potency and safety. years ago, noninfectious diseases were mainly treated with synthetic compounds. despite testing thousands of synthetic chemicals, only a handful of promising structures was obtained. as new synthetic lead compounds became extremely diffi cult to fi nd, microbial products came into play. poor or toxic antibiotics produced by fungi such as cyclosporin a or mycotoxins such as ergot alkaloids, gibberellins, zearelanone were then successfully applied in medicine and agriculture. this led to the use of fungal products as immunosuppressive agents, hypocholesterolemic drugs, antitumor agents, and for other applications. only about % of cholesterol in humans comes from the diet. the rest is synthesized by the body, predominantly in the liver. many people cannot control their level of cholesterol at a healthy level by diet alone and require hypocholesterolemic agents. high blood cholesterol leads to atherosclerosis, which is a chronic, progressive disease characterized by continuous accumulation of atheromatous plaque within the arterial wall, causing stenosis and ischemia. atherosclerosis is a leading cause of human death. the last two decades have witnessed the introduction of a variety of anti-atherosclerotic therapies. the statins form a class of hypolipidemic drugs, formed as secondary metabolites by fungi, and used to lower cholesterol by inhibiting the rate-limiting enzyme of the mevalonate pathway of cholesterol biosynthesis; i.e., -hydroxymethyl glutaryl-coa (hmg-coa) reductase. inhibition of this enzyme in the liver stimulates low-density lipoprotein (ldl) receptors, resulting in an increased clearance of ldl from the bloodstream and a decrease in blood cholesterol levels. they can reduce total plasma cholesterol by - %. through their cholesterol-lowering effect, they reduce risk of cardiovascular disease, prevent stroke, and reduce development of peripheral vascular disease [ ] . currently, there are a number of statins in clinical use. they reached an annual market of nearly $ billion before one became a generic pharmaceutical. the history of the statins has been described by akira endo, the discoverer of the fi rst statin, compactin (mevastatin; ml- b) [ ] . this fi rst member of the group was isolated as an antibiotic product of penicillium brevicompactum [ ] . at about the same time, it was found by endo and coworkers as a cholesterolemic product of penicillium citrinum [ ] . although compactin was not of commercial importance, its derivatives achieved strong medical and commercial success. lovastatin (monacolin k; mevinolin; mevacor tm ), was isolated in broths of monascus rubra and aspergillus terreus [ , ] . lovastatin, developed by merck & co. and approved by the us food and drug administration (fda) in , was the fi rst commercially marketed statin. in its chemical structure, lovastatin has a hexahydronaphthalene skeleton substituted with a p -hydroxy-lactone moiety ( fig. . ) . a semisynthetic derivative of lovastatin is zocor® (simvastatin), one of the main hypocholesterolemic drugs, selling for $ billion per year before becoming generic. an unexpected effect of simvastatin is its benefi cial activity on pulmonary artery hypertension [ ] . another surprising effect is its antiviral activity [ ] . simvastatin is active against rna viruses and acts as monotherapy against chronic hepatitis c virus in humans. it has been shown to act in vitro against hepatitis b virus (hbv). this virus infects million people and is the most common infectious disease agent in the world. the virus causes hepatocellular cancer, which is the leading cause of cancer death. nucleotide analogs (lamivudine, adefovir, tenofovir, entecavir, telbuvidine) were approved for hbv infections but they only work on - % of patients. simvastatin is synergistic with these nucleotide analogs. statins also have antithrombotic, anti-infl ammatory, and antioxidant effects [ ] . they have shown activity against multiple sclerosis, artherosclerosis, alzheimer's disease, and ischemic stroke [ , ] . however, these applications have not yet been approved since more clinical studies are required. the neuroprotective effect of statins has been demonstrated in an in vitro model of alzheimer's disease using primary cultures of cortical neurons [ ] . the effect did not appear to be due to cholesterol lowering but rather to reduction in formation of isoprenyl intermediates of the cholesterol biosynthetic process. lovastatin has shown antitumor activity against embryonal carcinoma and neuroblastoma cells [ ] . although simvastatin is usually made from lovastatin chemically in a multistep process, an enzymatic/bioconversion process using recombinant escherichia coli has been developed [ ] . another statin, pravastatin ($ . billion in sales per year), is made via different biotransformation processes from compactin by streptomyces carbophilus [ ] and actinomadura sp. [ ] . other genera involved in production of statins are doratomyces, eupenicillium, gymnoascus, hypomyces, paecilomyces, phoma, trichoderma, and pleurotus [ ] . a synthetic compound, modeled from the structure of the natural statins, is lipitor®, which was the leading drug of the entire pharmaceutical industry in terms of market (about $ billion per year) for many years. more than million new cases of cancer were diagnosed in the world in ; . million cases were in men and . million in women, resulting in . million cancerrelated deaths. the tumor types with the highest incidence were lung ( . %), breast ( . %), and colorectal ( . %). some of the anticancer drugs in clinical use are secondary metabolites derived from plants and fungi. among the approved products are taxol and camptothecin. taxol (paclitaxel) was fi rst isolated from the pacifi c yew tree, taxus brevifolia [ ] and later found to be a fungal secondary metabolite [ ] . it is a steroidal alkaloid diterpene alkaloid that has a characteristic n -benzoylphenyl isoserine side chain and a tetracycline ring ( fig. . ) . it inhibits rapidly dividing mammalian cancer cells by promoting tubulin polymerization and interfering with normal microtubule breakdown during cell division. the benzoyl group of the molecule is particularly crucial for maintaining the strong bioactivity of taxol. the drug also inhibits several fungi (species of pythium, phytophthora, aphanomyces ) by the same mechanism. in , taxol was approved for refractory ovarian cancer and today is used against breast cancer and advanced forms of kaposi's sarcoma [ ] . a formulation in which paclitaxel is bound to albumin is sold under the trademark abraxane ® . taxol sales amounted to $ . billion in for bristol myers-squibb, representing % of the company's pharmaceutical sales and its third largest selling product. it has reached $ . billion annual sales in international markets. although synthetic methods for taxol production have been tried, the chemical molecular structure is so complex that commercial synthetic production is unfeasible. currently, italy, the uk, the netherlands, and other western countries are engaged in the production of taxol by plant cell fermentation technology. taxol production by plant cell culture of taxus sp. was reported to be at mg l − [ ] . however, addition of methyl jasmonate, a plant signal transducer, increased production to mg l − . as stated previously, taxol has also been found to be a fungal metabolite [ , ] . fungi such as taxomyces andreanae, pestalotiopsis microspora , tubercularia sp., phyllosticta citricarpa, nodulisporium sylviforme , colletotrichum gloeosporoides, colletotrichum annutum, fusarium maire , and pestalotiopsis versicolor produce it [ , - ] . the endophyte f. maire produces μg l − . production by p. citricarpa amounted to μg l − [ ] . production was reported at μg l − by submerged fermentation with an engineered strain of the endophytic fungus ozonium sp. (efy- ). the transformed strain overproduced the rate-limiting enzyme of taxol biosynthesis, taxadiene synthase [ ] . another endophytic fungus, phoma betae , isolated from the medicinal tree ginkgo biloba , produced taxol at μg l − [ ] . cladosporium cladosporoides , an endophyte of the taxus media tree, produced μg l − of taxol [ ] . metarhizium anisopiliae h- , isolated from the tree taxus chinensis , yielded μg l − [ ] . although a review of taxol production by endophytic fungi indicated that strain improvement had resulted in levels of only . - . mg l − [ ] , it was reported that another fungus, alternaria alternate var. monosporus , from the bark of taxus yunanensis , after ultraviolet and nitrosoguanidine mutagenesis, could produce taxol at mg l − [ ] . the endophytic fungus p. versicolor , from the plant taxus cuspidata , produced μg l − [ ] and c. annutum from capsicum annuum made μg l − [ ] . another important antitumor agent is camptothecin, a modifi ed monoterpene indole alkaloid produced by certain plants (angiosperms) and by the endophytic fungus, entrophospora infrequens . the fungus was isolated from the plant fig. . chemical structure of taxol. the benzoyl group is located in the left side of the structure nathapodytes foetida [ ] . in view of the low concentration of camptothecin in tree roots and poor yield from chemical synthesis, the fungal fermentation is very promising for industrial production of camptothecin. it is used for recurrent colon cancer and has unusual activity against lung, ovarian, and uterine cancer [ ] . colon cancer is the second-leading cause of cancer fatalities in the usa and the third most common cancer among us citizens. camptothecin is known commercially as camptosar and campto and achieved sales of $ billion in [ ] . camptothecin's watersoluble derivatives irinotecan and topotecan have been approved and are used clinically. metastatic colorectal cancer is treated by irinotecan whereas topotecan has use for ovarian cancer, cervical cancer, and small-cell lung cancer. a review of the activities of camptothecin and its many small and macromolecular derivatives has been published by venditto and simanek [ ] . the cellular target of camptothecin is type i dna topoisomerase. when patients become resistant to irinotecan, its use can be prolonged by combining it with the monoclonal antibody erbitux (cetuximab). erbitux blocks a protein that stimulates tumor growth and the combination helps metastatic colorectal cancer patients expressing epidermal growth factor receptor (egfr). this protein is expressed in % of advanced metastatic colorectal cancers. the drug combination reduces invasion of normal tissues by tumor cells and the spread of tumors to new areas. angiogenesis, the recruitment of new blood vessels, is necessary for tumors to obtain oxygen and nutrients. tumors actively secrete growth factors that trigger angiogenesis. anti-angiogenesis therapy is now known as one of four cancer treatments; the other three are surgery, radiotherapy, and chemotherapy. by the end of , anti-angiogenesis drugs were in phase iii clinical trials and more than were in phase ii. fumagillin, a secondary metabolite of aspergillus fumigatus , was one of the fi rst agents found to act as an anti-angiogenesis compound. next to come along were its oxidation product ovalacin and the fumagillin analog tnp- (=agm- ). tnp- binds to and inhibits type methionine aminopeptidase. this interferes with amino-terminal processing of methionine, which may lead to inactivation of enzymes essential for growth of endothelial cells. in animal models, tnp- effectively treated many types of tumors and metastases. inhibitors of farnesyltransferase (ftis) have anticancer activity because farnesylation is required for activation of ras, a necessary step in cancer progression. they also induce apoptosis in cancer cells. the fungus phoma sp. fl- produces an fti known as tan- [ ] . an individual's immune system is capable of distinguishing between native and foreign antigens and to mount a response only against the latter. suppressor cells are critical in the regulation of the normal immune response. the suppression of the immune response, either by drugs or radiation, in order to prevent the rejection of grafts or transplants or to control autoimmune diseases, is called immunosuppression. microbial compounds capable of suppressing the immune response have been discovered as fungal secondary metabolites. cyclosporin a was originally discovered in the s as a narrow-spectrum antifungal peptide produced by the mold, tolypocladium nivenum (previously tolupocladium infl atum ) in an aerobic fermentation [ ] . cyclosporins are a family of neutral, highly lipophilic, cyclic undecapeptides containing some unusual amino acids, synthesized by a nonribosomal peptide synthetase, cyclosporin synthetase. discovery of the immunosuppressive activity of this secondary metabolite led to use in heart, liver, and kidney transplants and to the overwhelming success of the organ transplant fi eld [ ] . cyclosporin was approved for use in . it is thought to bind to the cytosolic protein cyclophilin (immunophilin) of immunocompetent lymphocytes, especially t -lymphocytes. this complex of cyclosporin and cyclophilin inhibits calcineurin, which under normal circumstances is responsible for activating the transcription of interleukin- . it also inhibits lymphokine production and interleukin release and therefore leads to a reduced function of effector t -cells. annual world sales of cyclosporin a are approximately $ billion. cyclosporin a also has activity against corona viruses [ ] . studies on the mode of action of cyclosporin, and the later-developed immunosuppressants from actinomycetes, such as sirolimus (a rapamycin) and fk- (tacrolimus), have markedly expanded current knowledge of t -cell activation and proliferation. these agents act by interacting with an intracellular protein (an immunophilin), thus forming a novel complex that selectively disrupts the signal transduction events of lymphocyte activation. their targets are inhibitors of signal transduction cascades in microbes and humans. in humans, the signal transduction pathway is required for activation of t cells. a very old broad-spectrum antibiotic, actually the fi rst antibiotic ever discovered, is mycophenolic acid, which has an interesting history. bartolomeo gosio ( - ), an italian physician, discovered the compound in [ ] . gosio isolated a fungus from spoiled corn, which he named penicillium glaucum , which was later reclassifi ed as p. brevicompactum . he isolated crystals of the compound from culture fi ltrates in and found it to inhibit growth of bacillus anthracis . this was the fi rst time an antibiotic had been crystallized and the fi rst time that a pure compound had ever been shown to have antibiotic activity. the work was forgotten but fortunately the compound was rediscovered by alsberg and black [ ] and given the name mycophenolic acid. they used a strain originally isolated from spoiled corn in italy called penicillium stoloniferum , a synonym of p. brevicompactum . the chemical structure was elucidated many years later ( ) by birkinshaw and coworkers [ ] in england. mycophenolic acid has antibacterial, antifungal, antiviral, antitumor, antipsoriasis, and immunosuppressive activities. its antiviral activity is exerted against yellow fever, dengue virus, and japanese encephalitis virus [ ] . it was never commercialized as an antibiotic because of its toxicity, but its -morpholinoethylester was approved as a new immunosuppressant for kidney transplantation in and for heart transplants in [ ] . the ester is called mycophenolate mofetil (cellcept) and is a prodrug that is hydrolyzed to mycophenolic acid in the body. it is sometimes used along with cyclosporin in kidney, liver, and heart transplants. mycophenolic acid also appears to have anti-angiogenic activity [ ] . fungi produce poisons called mycotoxins, which, strangely enough, have been harnessed as medically useful agents. these agents (e.g., ergot alkaloids) caused fatal poisoning of humans and animals (ergotism) for centuries by consumption of bread made from grain contaminated with species of the fungus claviceps . however, mycotoxins later were found useful for angina pectoris, hypertonia, serotoninrelated disturbances, inhibition of protein release in agalactorrhea, reduction in bleeding after childbirth, and prevention of implantation in early pregnancy [ , ] . their physiological activities include inhibition of action of adrenalin, noradrenalin, and serotonin, as well as the contraction of smooth muscles of the uterus. antibiotic activity is also possessed by some ergot alkaloids. members of the genus gibberella produce zearelanone and gibberellins. zearelanone is an estrogen made by gibbberella zeae (syn. fusarium graminearum ) [ ] . its reduced derivative zeranol is used as an anabolic agent in sheep and cattle, which increases growth and feed effi ciency. giberellic acid, a member of the mycotoxin group known as gibberellins, is a product of gibberella fujikori and causes "foolish rice seedling" disease in rice [ ] . gibberellins are employed to speed up the malting of barley, improve the quality of malt, increase the yield of vegetables, and cut the time in half for obtaining lettuce and sugar beet seed crops. they are isoprenoid growth regulators, controlling fl owering, seed germination, and stem elongation [ ] . more than t are produced annually with a market of over $ billion. enzyme inhibitors have received increased attention as useful tools, not only for the study of enzyme structures and reaction mechanisms, but also for potential utilization in medicine and agriculture. several enzyme inhibitors with various industrial uses have been isolated from microbes [ ] . among the most important are the statins and hypocholesterolemic drugs discussed previously. fungal products are also used as enzyme inhibitors against cancer, diabetes, poisoning, and alzheimer's disease. the enzymes inhibited include acetylcholinesterase, protein kinase, tyrosine kinase, glycosidases, and others [ ] . since ad, monascus purpurea has been grown on rice to prepare koji or angkak (red rice), which is used as a traditional chinese food and medicine [ ] . monascorubramine and rubropunctatin are water-soluble red pigments formed upon reaction of the orange pigments monascorubrin and rubropunctatin with amino acids in fermentation media [ ] . the fungus is used to prepare red rice, wine, soybean cheese, meat, and fi sh. it is authorized in japan and china for food use. there are known monascus pigments. they have an amazing number of activities: antimicrobial, anticancer, anti-mutagenesis, antidiabetes, anti-obesity, anti-infl ammatory, cholesterol-lowering, immunosuppressive, and hypotensive [ , ] . nutritional control of the formation of the red pigments has been described in a series of publications by lin and demain [ - ] . phaffi a rhodozyma ( xanthophyllomyces dendrorhous ) is a heterobasidiomycetous yeast that has become the most important microbial source for preparation of the carotenoid astaxanthin [ , ] . this oxygenated carotenoid pigment is used in the feed, food, and cosmetic industries. it is responsible for the orange to pink color of salmonid fl esh and the reddish color of boiled crustacean shells. feeding of penreared salmonids with a diet containing this yeast induces pigmentation of the white muscle [ ] . it is a very good antioxidant, times more active than beta-carotene and times more than alpha-tocopherol. it is the second most important carotenoid. astaxanthin enhances the immune system, and protects skin from radiation injury and cancer. it can be produced synthetically as hydroxyl-astaxanthin from petrochemicals with a selling price of $ , per kg. however, the natural product is favored because the synthetic product is a mixture of stereoisomers. natural astaxanthin is more stable than the synthetic version and more bioavailable. the natural product is present in algae and fi sh as mono-and di-esters of fatty acids. however, it is diffi cult to hydrolyze the esters from algae, which limits its usage to trout and salmon. the yeast product is better since it is the % free, non-esterifi ed ( r, 'r) stereoisomer. the natural product is more expensive ($ , per kg) than synthetic astaxanthin ($ , per kg). the astaxanthin market was $ million in with % being synthetic. most of the production processes with the yeast yield levels of astaxanthin lower than mg l − . however, white light improved production to mg l − [ ] and mutant strain ubv-ax can make mg l − [ ] . thaumatin, a protein produced by the plant thaumatococcus danielli , can also be produced by p. roqueforti and aspergillus niger var awamori [ ] . thaumatin is intensely sweet (i.e., , times sweeter than sucrose) and is approved as a foodgrade ingredient. production by a. niger var awamori was improved from mg l − up to mg l − by increasing gene dosage and use of a strong promoter [ ] . the sweetener xylitol, normally produced by pichia stipitis , can be produced by recombinant saccharomyces cerevisiae in higher concentrations by transforming the xyl gene of p. stipitis into s. cerevisiae . the gene encodes a xylose reductase [ ] . microorganisms have greatly contributed for about years to the development of medicine and agriculture. however, due to different situations, pathogenic microbes have become resistant to many antibiotics creating a dangerous situation and therefore the need for new antibiotics is imperative. unfortunately, most of the large pharmaceutical companies have abandoned the search for new antimicrobial compounds. due to economics, they have concluded that drugs directed against chronic diseases offer a better revenue stream than do antimicrobial agents, for which the length of treatment is short and government restriction is likely. some small pharmaceutical and biotechnology companies are still developing antibiotics but most depend on venture capital rather than sales income, and with the present regulations, face huge barriers to enter into the market. these barriers were raised with the best intentions of ensuring public safety but they are having the opposite effect; i.e., termination of antibiotic development while resistance continues to increase [ ] . however, there are some new bright possibilities. one of the more promising is the utilization of uncultivated microorganisms. considering that % of bacteria and % of fungi have not yet been cultivated in the laboratory, efforts to fi nd means to grow such uncultured microorganisms is proceeding and succeeding [ ] . furthermore, researchers are now extracting bacterial dna from soil samples, cloning large fragments into, for example, bacterial artifi cial chromosomes, expressing them in a host bacterium and screening the library for new antibiotics. this metagenomic effort could open up the exciting possibility of a large untapped pool from which new natural products could be discovered [ ] . another exciting possibility is that of genome mining [ ] . in addition to these relatively new techniques, chemical and biological modifi cation of old antibiotics could still supply new and powerful drugs. these comments also apply to non-antibiotics such as antitumor agents and other microbial products. in addition, natural products must continue to be tested for desirable therapeutic activities. i believe that signifi cant progress in identifying new antibiotics, oncology therapeutics, and other useful medicines will be made, probably not by the big pharmaceutical companies, but by biotechnology companies and small research groups from institutes and universities. biotechnological advantages of laboratory-scale solid-state fermentation with fungi bioactive microbial metabolites. a personal view fungal secondary metabolites. strategies to activate silent gene clusters industrial mycology: past, present, and future isolating "uncultivable" microorganisms in pure culture in a simulated natural environment fulfi lling the promise of biotechnology to market, to market- accurate prediction of secondary metabolite gene clusters in fi lamentous fungi fungal biotechnology regulation of fungal secondary metabolism signal-transduction cascades as targets for therapeutic intervention by natural products thiolactomycin and related analogues as novel anti-mycobacterial agents targeting kasa and kasb condensing enzymes in mycobacterium tuberculosis the combinatorial chemistry of nature are actinomycetes exhausted as a source of secondary metabolites? industrial antibiotics: today and the future nutritional and engineering aspects of microbial process development a novel impeller confi guration to improve fungal physiology performance and energy conservation for cephalosporin c production pharmaceutical and biotech fi rms taking on drug-resistant microbes activities of tmc , rifampin, and pyrazinamide against mycobacterium tuberculosis infection in guinea pigs inhibition of fatty acid synthetases by the antibiotic cerulenin statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis a historical perspective on the discovery of statins crystal and molecular structure of compactin: a new antifungal metabolite from penicillium brevicompactum ml- b and ml- c, new inhibitors of cholesterolgenesis produced by penicillium citrinin mevinolin, a highly potent competitive inhibitor of hydroxylmethylglutarylcoenzyme a reductase and a cholesterol-lowering agent a new hypocholesterolemic agent produced by monascus species simvastatin has benefi cial effect on pulmonary artery hypertension by inhibiting nf-kb expression fluvastatin inhibits hepatitis c replication in humans the pleiotropic effects of statins and omega- fatty acids against sepsis: a new perspective statins-a cure-all for the brain? statins: -hydroxy- -methylglutaryl-coa (hmg-coa) reductase inhibitors demonstrate anti-atherosclerotic character due to their antioxidant capacity neuroprotective effect of statins in an in vitro model of alzheimer's disease lovastatin induces neuronal differentiation and apoptosis of embryonal carcinoma and neuroblastoma cells: enhanced differentiation and apoptosis in combination with dbcamp effi cient synthesis of simvastatin by use of whole-cell biocatalysts a two-component-type cytochrome p- monooxygenase system in a prokaryote that catalyzes hydroxylation of ml- b to pravastatin, a tissue-selective inhibitor of -hydroxy- -methylglutaryl coenzyme a reductase a new hydroxylase system in actinomadura sp. cells converting compactin to pravastatin production and purifi cation of statins from pleurotus ostreatus (basidiomycetes) strains camptothecin and taxol: from discovery to clinic taxol and taxane production by taxomyces andreanae , an endophytic fungus of pacifi c yew natural products as sources of new drugs over the last years in vitro culture of taxus sp.: strategies to increase cell growth and taxoid production microbial paclitaxel: advances and perspectives isolation of colletotrichum gloeosporiodes , a novel endophytic taxol-producing fungus from the leaves of a medicinal plant taxol promising fungal endophyte, pestalotiopsis species isolated from taxus cuspidata in vitro screening of taxol, an anticancer drug produced by the fungus colletotricum capsici endophytic taxol-producing fungi from bald cypress taxol from tubercularia sp. strain tf , an endophytic fungus of taxus mairei strain improvement and optimization of the media of taxolproducing fungus fusarium maire study on the preparation and regeneration of protoplast from taxol-producing fungus nodulisporium sylviforme taxol from phyllosticta citricarpa , a leaf spot fungus of the angiosperm citrus medica engineering taxol biosynthetic pathway for improving taxol yield in taxol-producing endophytic fungus efy- ( ozonium sp.) isolation of taxol, an anticancer drug produced by the endophytic fungus, phoma betae an endophytic taxol-producing fungus from taxus media, cladosporium cladosporoides md isolation and characterization of endophytic taxol-producing fungi from taxus chinensis a review: recent advances and future prospects of taxolproducing endophytic fungi screening the high-yield paclitaxel producing strain alternaria alternate var monosporus bioreactor studies on the endophytic fungus entrophospora for the production of an anticancer alkaloid camptothecin camptothecin, over four decades of surprising fi ndings cancer therapies utilizing the camptothecins: a review of the in vivo literature microbial-based therapy of cancer. current progress and future prospects biological effects of cyclosporine a: a new antilymphocytic agent history of the discovery of cyclosporin and of its early pharmacological development cyclosporin a inhibits the replication of diverse coronaviruses an appreciation usda bur plant ind, bull no. , washington: government printing offi ce studies in the biochemistry of micro-organisms. . the molecular constitution of mycophenolic acid, a metabolic product of penicillium brevicompactum dierckx. part . further observations on the structural formula for mycophenolic acid mycophenolic acid inhibits replication of japanese encephalitis virus bioavailability improvement of mycophenolic acid through amino ester derivatization identifi cation of type inosine monophosphate dehydrogenase as an antiangiogenic drug target microbial secondary metabolites play important roles in medicine: prospects to discovery of new drugs london: academic; zearelanone and some derivatives: production and biological activities the gibberellin fermentation biosynthesis of gibberellins in gibberella fujikuroi : biomolecular aspects enzyme inhibitors of microbial origin fungal enzyme inhibitors as pharmaceuticals, toxins and scourge of pcr constituents of red yeast rice, a traditional chinese food and medicine secondary metabolites of the fungus monascus : a review monascus pigments benefi t of monascus -fermented products for hypertension prevention: a review effect of nutrition of monascus on formation of red pigments resting cell studies on formation of water-soluble red pigments by monascus sp leucine interference in the production of water-soluble red monascus pigments negative effect of ammonium nitrate as nitrogen source on the production of water-soluble red pigments by monascus sp carotenoids of phaffi a rhodozyma , a red-pigmented fermenting yeast xanthophyllomyces dendrorhous for the industrial production of astaxanthin phaffi a rhodozyma as an astaxanthin source in animal diets high-titer production of astaxanthin by the semi-industrial fermentation of xanthophyllomyces dendrorhous astaxanthin over-producing strains of phaffi a rhodozyma. method for their cultivation and their use in animal feeds. us patent recent developments in the characterization and biotechnological production of sweettasting proteins thaumatin production in aspergillus awamori by use of expression cassettes with strong fungal promoters and high gene dosage xylitol production by recombinant saccharomyces cerevisiae the need for new antibiotics new antibiotics from bacterial natural products antimicrobials, drug discovery, and genome mining key: cord- - hlwwdh authors: quarantelli, e. l.; boin, arjen; lagadec, patrick title: studying future disasters and crises: a heuristic approach date: - - journal: handbook of disaster research doi: . / - - - - _ sha: doc_id: cord_uid: hlwwdh over time, new types of crises and disasters have emerged. we argue that new types of adversity will continue to emerge. in this chapter, we offer a framework to study and interpret new forms of crises and disasters. this framework is informed by historical insights on societal interpretations of crises and disasters. we are particularly focused here on the rise of transboundary crises – those crises that traverse boundaries between countries and policy systems. we identify the characteristics of these transboundary disruptions, sketch a few scenarios and explore the societal vulnerabilities to this type of threat. we end by discussing some possible implications for planning and preparation practices. disasters and crises are as old as when human beings started to live in groups. through the centuries, new types have emerged. for instance, the development of synthetic chemicals in the th century and nuclear power in the th century created the possibility of toxic chemical disasters and crises from radioactive fallouts. older crisis types did not disappear: ancient types such as floods and earthquakes remain with us. the newer disasters and crises are additions to older forms; they recombine elements of old threats and new vulnerabilities. the literature on crisis and disaster research suggests that we are at another important historical juncture with the emergence of a new distinctive class of disasters and crises not often seen before (ansell, boin, & keller, ; helsloot, boin, jacobs, & comfort, ; tierney, ) . in this chapter, we discuss the rise of transboundary crises and disasters. we seek to offer a heuristic approach to studying these new crises and disasters. we offer a heuristic approach to understanding the disasters and crises of the future. it is presented primarily as an aid or guide to looking further into the matter, hopefully stimulating more investigation on conceptions of disasters and crises in the past, the present, and the future. unlike in some areas of scientific inquiry, where seemingly final conclusions can be reached (e.g., about the speed of light), the basic nature of the phenomenon we are discussing is of a dynamic nature and subject to change through time. the answer to the question of what is a disaster or crisis has evolved and will continue to do so (see perry' s chapter in this handbook). human societies have always been faced with risks and hazards. earthquakes, hostile inter-and intra-group relationships, massive floods, sudden epidemics, threats to take multiple hostages or massacre large number of persons, avalanches, fires and tsunamis have marked human history for centuries if not eons. disasters and crises requiring a group reaction are as old as when human beings started to live in stable communities. the earliest happenings are attested to in legends and myths, oral traditions and folk songs, religious accounts and archeological evidence from many different cultures and subcultures around the world. for example, a "great flood" story has long existed in many places (lang, ) . as human societies evolved, new threats and hazards emerged. to the old there have been added new dangers and perils that increasingly have become potentially dangerous to human groups. risky technological agents have been added to natural hazards. these involve chemical, nuclear and biological threats that can accidentally materialize as disasters. intentional conflict situations have become more damaging at least in the sense of involving more and more victims. the last years have seen two world wars, massive air and missile attacks by the military on civilians distant from battle areas, many terrorist attacks, and widespread ethnic strife. genocide killed one million persons in rwanda; millions have become refugees and tens of thousands have died in darfur in the sudan in africa. while terrorism is not a new phenomenon, its targets have considerably expanded. some scholars and academics have argued that the very attempt to cope with increasing risks, especially of a technological nature, is indirectly generating new hazards. as the human race has increasingly been able to cope with such basic needs as food and shelter, some of the very coping mechanisms involved (such as the double edged consequences of agricultural pesticides), have generated new risks for human societies (beck, ; perrow, ) . for example, in , toxic chemicals were successfully used to eradicate massive locust infestations affecting ten western and northern african countries. those very chemicals had other widespread negative effects on humans, animals and crops (irin, ) . implicit in this line of thinking is the argument that double-edged consequences from new innovations (such as the use of chemicals, nuclear power and genetic engineering) will continue to appear (tenner, ) . we cannot say that the future will bring more disasters, as we have no reliable statistics on prior happenings as a base line to use in counting (quarantelli, ) . at present, it would seem safer to argue that some future events are qualitatively different, and not necessarily that there will be more of them in total (although we would argue the last is a viable hypothesis that requires a good statistical analysis). societies for the most part have not been passive in the face of these dangers to human life and well-being. this is somewhat contrary to what is implicit in much of the social science literature especially about disasters. in fact, some of these writings directly or indirectly state that a fatalistic attitude prevailed in the early stages of societal development (e.g., quarantelli, ) . this was thought because religious beliefs attributed negative societal happenings to punishments or tests this seems to have occurred about five to six thousand years ago (see lenski, lenski, & nolan, ) . however, recent archeological studies suggest that humans started to abandon nomadic wanderings and settled into permanent sites around , years ago (balter, ) so community recognized disasters and crises might have an even longer history. by supernatural entities (the "acts of god" notion, although this particular phrase became a common usage mostly because it served the interests of insurance companies). but prayers, offerings and rituals are widely seen as means to influence the supernatural. so passivity is not an automatic response to disasters and crises even by religious believers, an observation sometimes unnoticed by secular researchers. in fact, historical studies strongly indicate that societal interpretations have been more differentiated than once believed and have shifted through the centuries, at least in the western world. in ancient greece, aristotle categorized disasters as the result of natural phenomena and not manifestations of supernatural interventions (aristotle, ) . the spread of christianity about , years ago helped foster the belief that disasters were "special providences sent directly" from "god to punish sinners" (mulcahy, , p. ) . in the middle ages, even scholars and educated elites "no longer questioned the holy origins of natural disasters" (massard-guilbaud, platt, & schott, , p. ) . starting in the th century, however, explanations started to be replaced by "ones that viewed disasters as accidental or natural events" (mulcahy, , p. ) . this, of course, also reflected a strong secularization trend in western societies. perhaps this reached a climax with the lisbon earthquake which dynes notes can be seen as the "first modern disaster" ( , p. ). so far our discussion has been mostly from the perspective of the educated elites in western societies. little scholarly attention seems to have been given to what developed in non-western social systems. one passing observation about the ottoman empire and fire disasters suggests that the pattern just discussed might not be universal. thus, while fire prevention measures were encouraged in cities, they were not mandated "since calamities were considered" as expressions of the will of god (yerolympos, , p. ) . even as late as an ottoman urban building code stated that according to religious writing "the will of the almighty will be done" and nothing can and should be done about that. at the same time, this code advances the idea that nevertheless there were protective measures that could be taken against fires that are "the will of allah" (quoted in yerolympos, , p. ) . of course, incompatibility between natural and supernatural views about the world are not unique to disaster and crisis phenomena, but that still leaves the distinction important. even recently, an australian disaster researcher asserted that in the southwestern asian tsunami most of the population seemed to believe that the disaster was "sent either as a test of faith or punishment" (mcaneney, , p. ). or as another writer noted, following the tsunami, religiously oriented views surfaced. some were by: "fundamentalist christians" who tend to view all disasters "as a harbinger of the apocalypse". others were by "radical islamists" who are inclined to see any disaster that "washes the beaches clear of half-nude tourists to be divine" (neiman, , p. ) . after hurricane katrina, some leaders of evangelical groups spoke of the disaster as punishment imposed by god for "national sins" (cooperman, ) . in the absence of systematic studies, probably the best hypothesis that should be researched is that at present religious interpretations about disasters and crisis still appear to be widely held, but relative to the past probably have eroded among people in general. the orientation is almost certainly affected by sharp cross-societal difference in the importance attributed to religion as can be noted in the religious belief systems and practices as currently exist in the united states and many islamic countries, compared to japan or a highly secular western europe. apart from the varying interpretations of the phenomena, how have societies behaviorally reacted to existing and ever-changing threats and risks? as a whole, human groups have evolved a for an interesting attempt to deal with these two perspectives see the paper entitled disaster: a reality or a construct? perspective from the east, written by jigyasu ( ) an indian scholar. variety of formal and informal mechanisms to prevent and to deal with crises and disasters. but societies have followed different directions depending on the perceived sources of disasters and crises. responses tend to differ with the perception of the primary origin (the supernatural, the natural or the human sphere). for example, floods were seen long ago as a continuing problem that required a collective response involving engineering measures. stories that a chinese emperor, centuries before christ, deepened the ever-flooding yellow river by massive dredging and the building of diversion canals may be more legend than fact (waterbury, , p. ) . however, there is clear evidence that in egypt in the th century bc, the th dynasty pharaoh, amenemher ii completed southwest of cairo what was probably history's first substantial river control project (an irrigation canal and dam with sluice gates). other documentary evidence indicates that dams for flood control purposes were built as far back as b c in greece (schnitter, , p. , - ) . such mitigatory efforts indicate both the belief that there was a long-term natural risk as well as one that could be coped with by physically altering structural dimensions. later, particular in europe, there were many recurrent efforts to institute mitigation measures. for example, earthquake resistant building techniques were developed in ancient rome, although "they had been forgotten by the middle ages" (massard-guilbaud et al., , p. ) . the threats from floods and fires spurred mitigation efforts in greece. starting in the th century, developing urban areas devised many safeguards against fires, varying from regulations regarding inflammable items to storage of water for firefighting purposes. in many towns in medieval poland, dams, dikes and piles along riverbanks were built (sowina, ) . of course, actions taken were not always successful. but, if nothing else, these examples show that organized mitigation efforts have been undertaken for a long time in human history. there have been two other major behavioral trends of long duration that are really preventive in intent if not always in reality. one has been the routinization of responses by emergency oriented groups so as to prevent emergencies from escalating into disasters or crises. for example, in ancient rome, the first groups informally set up to fight fires were composed of untrained slaves. but when a fire in a.d. burned almost a quarter of rome, a corps of vigiles was created that had full-time personnel and specialized equipment. in more recent times, there are good examples of this routinization in the planning of public utilities that have standardized operating procedures to deal with everyday emergencies so as to prevent them from materializing into disasters. in the conflict area, there are various un and other international organizations, such as the international atomic energy agency and the european union (eu), that also try to head off the development of crises. in short, societies have continually evolved groups and procedures to try to prevent old and new risks and threats from escalating into disasters and crises. a second more recent major trend has been the development of specific organizations to deal first with wartime crises and then with peacetime disasters. societies for about a century have been creating specific organizations to deal first with new risks for civilians created by changes in warfare, and then improving on these new groups as they have been extended to peacetime situations. rooted in civil defense groups created for air raid situations, there has since been the evolvement of civilian emergency management agencies (blanchard, ) . accompanying this has been the start of the professionalization of disaster planners and crisis managers. there has been a notable shift from the involvement of amateurs to educated professionals. human societies adjusted not only to the early risks and hazards, but also to the newer ones that appeared up to the last century. the very existence of the human race is testimony to the social coping mechanisms of humans as they face such threats. here and there a few communities and groups have not been able to cope with the manifestations of contemporary risks and hazards (diamond, ) . but these have been very rare cases. neither disasters nor crises involving conflict have had that much effect on the continuing existence of cities anywhere in the world. throughout history, many cities have been destroyed. they have been: "sacked, shaken, burned, bombed, flooded, starved, irradiated and poisoned", but in almost every case they have phoenix-like been reestablished (vale & campanella, , p. ) . around the world, from the th to the th century, only cities were "permanently abandoned following destruction" (vale & campanella, , p. ) . the same analysis notes that large cities such as baghdad, moscow, aleppo, mexico city, budapest, dresden, tokyo, hiroshima and nagasaki all suffered massive physical destruction and lost huge numbers of their populations due to disasters and wartime attacks. all were rebuilt and rebounded. at the start of the th century, "such resilience became a nearly universal fact" about urban settlements around the world (vale & campanella, , p. ) . looking at these cities today as well as warsaw, berlin, hamburg and new orleans, it seems this recuperative tendency is very strong (see also schneider & susser, ) . in the hiroshima museum that now exists at the exact point where the bomb fell, there is a -degree photograph of the zone around that point, taken a few days after the attack. except for a few piles of ruins, there is nothing but rubble as far as the eye can see in every direction. there were statements made that this would be the scene at that location for decades. but a visitor to the museum today can see in the windows behind the circular photograph, many signs of a bustling city and its population (for a description of the museum see webb, ) . hiroshima did receive much help and aid to rebuild. but the city came back in ways that observers at the time of impact did not foresee. early efforts to understand and to cope with disasters and crises were generally of an ad hoc nature. with the strong development of science in the th century, there was the start of understanding the physical aspects of natural disasters, and these had some influence on structural mitigation measures that were undertaken. however, the systematic social science study of crises and disasters is about a half-century-old (fritz, ; kreps, ; quarantelli, quarantelli, , schorr, ; wright & rossi, ) . in short, there is currently a solid body of research-generated knowledge developed over the last half century of continuing and ever increasing studies around the world in different social science disciplines. to be sure, such accounts and reports are somewhat selective and not complete. there are now case studies and analytical reports on natural and technological disaster (and to some extent on other crises) numbering in the four figures. in addition, there are numerous impressions of specific behavioral dimensions that have been derived from field research (for summaries and inventories see alexander, ; cutter, ; dynes, demarchi, & pelanda, ; dynes & tierney, ; farazmand, ; helsloot, boin, jacobs, & comfort, ; mileti, ; oliver-smith, ; perry, lindell, & prater, ; rosenthal, boin, & comfort, ; rosenthal, charles, & 't hart, ; tierney, lindell, & perry, ; turner, ) . what are the distinctive aspects of the newer disasters and crises that are not seen in traditional ones? to answer this question, we considered what social science studies and reports had found about behavior in disasters and crises up to the present time. we then implicitly compared those observations and findings with the distinctive behavioral aspects of the newer disasters and crises. one issue that has always interested researchers and scholars is how to conceptualize disasters and crises. there is far from full agreement that all disasters and crises can be categorized together as being relatively homogeneous phenomena (quarantelli, ; perry & quarantelli, ) . this is despite the fact that there have been a number of attempts to distinguish between, among and within different kinds of disasters and crises. however, no one overall view has won anywhere near general acceptance among self-designated disaster and crisis researchers. to illustrate we will briefly note some of the major formulations advanced. for example, one attempt has been to distinguish between natural and technological disasters (erikson, ; picou & gill, ) . the basic assumption was that the inherent nature of the agent involved made a difference. implicit was the idea that technological dangers or threats present a different and more varying kind of challenge to human societies than do natural hazards or risks. most researchers have since dropped the distinction as hazards have come to be seen as less important than the social setting in which they appear. in recent major volumes on what is a disaster (quarantelli, ; perry & quarantelli, ) , the distinction was not even mentioned by most of the two dozen scholars who addressed the basic question. other scholars have struggled with the notion that there may be some important differences between what can be called "disasters" and "crises". the assumption here is that different community level social phenomena are involved, depending on the referent. thus, some scholars distinguish between consensus and conflict types of crises (stallings, tries to reconcile the two perspectives). in some research circles, almost all natural and most technological disasters are viewed as consensus types of crises (quarantelli, ) . these are contrasted with crises involving conflict such as are exemplified by riots, terrorist attacks, and ethnic cleansings and intergroup clashes. in the latter type, at least one major party is either trying to make it worse or to extend the duration of the crisis. in natural and technological disasters, no one deliberately wants to make the situation worse or create more damage or fatalities. now, there can be disputes or serious disagreements in natural or technological disasters. it is almost inevitable that there will be some personal, organizational and community conflicts as, for example, in the recovery phase of disasters, where scapegoating is common (bucher, ; drabek & quarantelli, cf. boin, mcconnell, & 't hart, ) . in some crises, the overall intent of major social actors is to deliberately attempt to generate conflict. in contrast to the unfolding sequential process of natural disasters, terrorist groups or protesting rioters not only intentionally seek to disrupt social life, they modify or delay their attacks depending on perceived countermeasures. apart from a simple observable logical distinction between consensus and conflict types of crises, empirical studies have also established behavioral differences. for example, looting behavior is distinctively different in the two types. in the typical disaster in western societies, almost always looting is rare, covert and socially condemned, done by individuals, and involves targets of opportunity. in contrast, in many conflict crises looting is very common, overt and socially supported, undertaken by established groups of relatives or friends, and involves deliberately targeted locations (quarantelli & dynes, ) . likewise, there are major differences in hospital activities in the two kinds of crises, with more variation in conflict situations. there are differences also in the extent to which both organizational and community-level changes occur as a result of consensus and conflict crises, with more changes resulting from conflict occasions (quarantelli, ) . finally, it has been suggested that the mass media system operates differently in terrorism situations and in natural and technological disasters (project for excellence in journalism, journalism, , . both the oklahoma city bombing and the - world trade center attack led to sharp clashes between different groups of initial organizational responders. there were those who saw these happenings primarily as criminal attacks necessitating closure of the location as a crime for a contrary view that sees terrorist occasions as more or less being the same as what behaviorally appears in natural and technological disasters (fischer, ) . scene, and those who saw them primarily as situations where priority ought to be on rescuing survivors. in the - situation, the clash continued later into the issues of the handling of dead bodies and debris clearance. all this goes to show that crises and disasters are socially constructed. whether it is by theorists, researchers, operational personnel, politicians or citizens, any designation comes from the construction process and is not inherent in the phenomena itself. this is well illustrated in an article by cunningham ( ) where he shows that a major cyanide spill into the danube river was differently defined as an incident, an accident, or a catastrophe, depending on how culpability was perceived and who was doing the defining. still other distinctions have been made. some advocate "crisis" as the central concept in description and analysis (see the chapter of boin, kuipers and 't hart in this handbook). in this line of thinking, a crisis involves an urgent threat to the core functions of a social system. a disaster is seen as "a crisis with a bad ending" (boin, ) . this is consistent with the earlier expressed idea that while there are many hazards and risks, only a few actually manifest themselves. but the crisis idea does not differentiate among the manifestations themselves as the consensus and conflict distinction does. this is not the place to try and settle conceptual disagreements and we will not attempt to do so. anyone in these areas of study should acknowledge that there are different views and different proponents should try to make their positions as explicit as possible so people do not continue to talk past one another. it is perhaps not amiss here to note that the very words or terms used to designate the core nature of the phenomena are etymologically very complex with major shifts in meaning through time. we are far from having standardized terms and similar connotations and denotations for them. a conceptual question that has come increasingly to the fore in the last decade or so is the question: have new kinds of crises and disasters began to appear? we think it is fair to say that there are new types of risks and hazards. there are also structural changes in social settings. together, they raise the prospect of new types of disasters and crises. for example, we have seen the breakdown of modern transportation systems (think of the volcanic ash crisis that paralyzed air traffic in ; kuipers & boin, ) . there have been massive information system failures either through sabotage or as a result of technical breakdowns in linked systems. there have been terrorist attacks of a magnitude and scale not seen before. we are living with the prospect of widespread illnesses and health-related difficulties that appear to be qualitatively different from traditional medical problems. we have just lived through financial and economic collapses that cut across different social systems around the world. many of these "new" disruptions have both traditional and non-traditional features: think of the heat waves in paris (lagadec, ) and chicago (klinenberg, ) , the ice storms in canada (scanlon, ) , but also the genocide-like violence in africa and the former yugoslavia. the chernobyl radiation fallout ( ) led some scholars and researchers to start asking if there was not something distinctively new about that disaster. the fallout was first openly measured in sweden. officials were mystified in that they could not locate any possible radiation source in their own country. later radiation effects on vegetation eaten by reindeer past the arctic circle in northern sweden were linked to the nuclear plant accident in the soviet union. the mysterious origins, crossing of national boundaries, and the emergent involvement of see safire ( ) who struggles with past and present etymological meanings of "disaster", "catastrophe", "calamity" and "cataclysm"; also see murria ( ) who looking outside the english language found a bewildering set of words used, many of which had no equivalent meanings in other languages. many european and transnational groups was not something researchers had typically seen together in other prior disasters. looking back, it is clear that certain other disasters also should have alerted all of us to the probability that new forms of adversity were emerging. in november , water used to put out fire in a plant involving agricultural chemicals spilled into the river rhine. the highly polluted river went through switzerland, germany, france, luxembourg and the netherlands. a series of massive fire smog episodes plagued indonesia in and . land speculations led to fire-clearing efforts that, partly because of drought conditions, resulted in forest fires that produced thick smog hazes that spread over much of southeast asia (barber & schweithelm, ) . these disrupted travel, which in turn affected tourism as well as creating respiratory health problems, and led to political criticism of indonesia by other countries as multi-nation efforts to cope with the problem were not very successful. both of these occasions had characteristics that were not typically seen in traditional disasters. in the original version of this chapter, we spoke about "trans-system social ruptures". this term was an extension of the earlier label of "social ruptures" advanced by lagadec ( lagadec ( , . the term "transboundary" has since become the more conventional way to describe crises and disasters that jump across different societal boundaries disrupting the social fabric of different social systems (ansell et al., ) . the two prime and initial examples we used in the original chapter were the severe acute respiratory syndrome (sars) and the sobig computer f virus spread, both of which appeared in . the first involved a "natural" phenomenon, whereas the second was intentionally created. since there is much descriptive literature available on both, we here provide only very brief statements about these phenomena. the new infectious disease sars appeared in the winter of . apparently jumping from animals to humans it originated in southern rural china, near the city of guangzhou. from there it moved through hong kong and southeast asia. it spread quickly around the world because international plane flights were shorter than its incubation period. at least infected persons died. it hit canada with outbreaks in vancouver in the west and toronto far away in the east. in time, persons died of the several hundred that got ill, and thousands of others were quarantined. the city's healthcare system virtually closed down except for the most urgent of cases with countless procedures being delayed or cancelled. the result was that there was widespread anxiety in the area resulting in the closing of schools, the cancellation of many meetings and, because visitors and tourists stayed away, a considerable negative effect on the economy (commission report, , p. ) . the commission report notes a lack of coordination among the multitude of private and public sector organizations involved, a lack of consistent information on what was really happening, and jurisdictional squabbling on who should be doing what. although sars vanished worldwide after june , to this day it is still not clear why it became so virulent in the initial outbreak and why it has disappeared (yardley, ) . the sobig computer f virus spread in august (schwartz, ) . it affected many computer systems and threatened almost all computers connected to the internet. the damage was very costly. a variety of organizations around the world, public and private, attempted to deal with the problem. initially uncoordinated, there eventually emerged in an informal way a degree of informational networking on how to cope with what was happening (koerner, ) . what can we generalize from not only these two cases, but also others that we looked at later in may , the so-called wannacry virus affected millions of computers across the world with ransomware. many hospitals were affected. (ansell et al., ) ? the characteristics we depict are stated in ideal-typical terms; that is, from a social science perspective, what the phenomena would be if they existed in pure or perfect form. first, the threat jumps across many international and national/political governmental boundaries. it crosses functional boundaries, jumping from one sector to another, and crossing from the private into public sectors (and sometimes back). there was, for example, the huge spatial leap of sars from a rural area in china to metropolitan toronto, canada. second, a transboundary threat can spread very fast. cases of sars went around the world in less than hours with a person who had been in china flying to canada quickly infecting persons in toronto. the spread of the sobig f virus was called the fastest ever (thompson, ) . this quick spread is accompanied by a very quick if not almost simultaneous global awareness of the risk because of mass media attention. third, there is no known central or clear point of origin, at least initially, along with the fact that the possible negative effects at first are far from clear. this stood out when sars first appeared in canada. there is much ambiguity as to what might happen. ambiguity is of course a major hallmark of disasters and crises (turner, ) . it is more pervasive in transboundary crises as information about causes, characteristics and consequences is distributed across the system. fourth, there are potentially if not actual large number of victims, directly or indirectly. the sobig computer virus infected % of email users in china, that is about million people and about three fourths of email messages around the world were infected by this virus (koerner, ) . in contrast to the geographic limits of most past disasters, the potential number of victims is often open ended in disruptions that span across boundaries. fifth, traditional "solutions" or approachesembedded in local and/or professional institutions will not always work. this is rather contrary to the current emphasis in emergency management philosophy. the prime and first locus of planning and managing cannot be the local community as it is presently understood. international and transnational organizations must typically be involved very early in the initial response (boin, ekengren, & rhinard, ) . the nation state may not even be a prime actor in the situation. sixth, although responding organizations and groups are major players, there is an exceptional amount of emergent behavior and the development of many informal ephemeral linkages. in some respects, the informal social networks generated, involving much information networking, are not always easily identifiable from the outside, even though they are often the crucial actors at the height of the crisis. in this section, we sketch several future scenarios that most likely would create transboundary disasters. even though some of the scenarios discussed might seem to be science fiction in nature, the possibilities we discuss are well within the realm of realistic scientific possibilities. the most obvious scenario revolves around asteroids or comets hitting planet earth (di justo, ) . this has, of course, happened in the past, but even more recent impacts found no or relatively few human beings around. there are two major possibilities with respect to impact (mcguire, ; wisner, ) . a landing in the ocean would trigger a tsunami-like impact in coastal areas. just the thinking of the possibility of how, when and where ahead of time coastal population evacuations might have to be undertaken, is a daunting thought. statistically less likely is a landing in a heavily populated area. but a terrestrial impact anywhere on land would generate very high quantities of dust in the atmosphere, which will affect food production as well as creating economic disruption. this would be akin to the tambora volcanic eruption in , which led to very cold summers and crop failures (post, ) . the planning and management problems for handling something like this would be enormous. the explosion of space shuttle columbia scattered debris over a large part of the united states. this relatively small disastercompared to a comet or asteroid impactinvolved massive crossing of boundaries, a large number of potential victims, and could not be managed by local community institutions. the response required that an unplanned effort coordinating organizations that had not previously worked with one another and other unfamiliar groups, public and private (ranging from the us forest service to local red cross volunteers to regional medical groups), be informally instituted over a great part of the united states (beck & plowman, ; donahue, ) . a second scenario is the inadvertent or deliberate creation of biotechnological disasters. genetic engineering of humans or food products is currently in its infancy. the possible good outcomes and products from such activity are tremendous (morton, ) and are spreading around the world (pollack, ) . but the double-edged possibilities mentioned earlier are also present. there is dispute over genetically modified crops, with many european countries resisting and preventing their use and spread in their countries. while no major disaster or crisis from this biotechnology has yet occurred, there have been many accidents and incidents that suggest that this will be only a matter of time. for example, in , starlink corn, approved only for animal feed is found in the food supply, such as taco shells and other groceries. the same year farmers in europe learned that that they had unknowingly been growing modified canola using mixed seed from canada. in , modified corn was found in mexico even though it was illegal to plant in that country. that same year, experimental corn that had been engineered to produce a pharmaceutical that was found in soybeans in the state of nebraska. in several places, organic farmers found that it was impossible for them to keep their fields uncontaminated (for further details about all these incidents and other examples, see pollack, ) . noticeable is the leaping of boundaries and uncertainty about the route of spreading. it does not take much imagination to see that a modified gene intended for restricted use, could escape and create a contamination that could wreak ecological and other havoc. perhaps even more disturbing to some is genetic engineering involving human beings. the worldwide dispute over cloning, while currently perhaps more a philosophical and moral issue, does also partly involve the concern over creating flawed human-like creatures. it is possible to visualize not far-fetched worst-case scenarios that could be rather disastrous. it should be noted that even when there is some prior knowledge of a very serious potential threat, what might happen is still likely to be as ambiguous and complex as when sars first surfaced. this can be seen in the continuing major concern expressed in to mid- about the possible pandemic spread of avian influenza, the so called "bird flu" (nuzzo, ; thorson & ekdahl, ) . knowledge of the evolution and spread of new pandemics, their effects and whether presently available protective measures would work, may well be very limited. knowledge that it might occur provides very little guidance on what might actually happen. it is possible to imagine the destruction of all food supplies for human beings either through the inadvertent or deliberate proliferation of very toxic biotechnological innovations for which no known barriers to spreading exists. these potential kinds of global disasters are of relatively recent origins and we may expect more such possibilities in the future. the human race is opening up potentially very catastrophic possibilities by innovations in nanotechnology, genetic engineering and robotics (barrat, ; joy, ; makridakis, ) . a potential is not an actuality. but it would be foolish from both a research as well as a planning and managing viewpoint to simply ignore these and other doomsday possibilities. the question might be asked if there is a built-in professional bias among disaster and crisis researchers and emergency planners to look for and to expect the worst (see mueller, for numerous examples). in the disaster and crisis area, this orientation is reinforced by the strong tendency of social critics and intellectuals to stress the negative. it would pay to look at the past, see what was projected at a particular time, and then to look at what actually happened. the worldwide expectations about what would happen at the turn of the century to computers are now simply remembered as the y k fiasco. it would be a worthy study to take projections by researchers about the future of ongoing crises and disasters, and then to look at what actually happened. in the s, in the united states, scholars made rough analyses about the immediate future course of racial and university riots in the country. their initial appearances had not been forecasted. moreover, there was a dismal record in predicting how such events would unfold (no one seemed to have foreseen that the riots would go from ghetto areas to university campuses), as well as that they rather abruptly stopped. we should be able to do a better job than we have so far in making projections about the future. but perhaps that is asking more of disaster and crisis researchers than is reasonable. after all, social scientists with expertise in certain areas, to take recent examples, failed completely to predict or forecast the non-violent demise of the soviet union, the peaceful transition in south africa, or the development of a market economy in communist china (cf. tetlock, ) . a disaster or crisis always occurs in some kind of social setting. by social setting we mean social systems. these systems can and do differ in social structures and cultural frameworks. there has been a bias in disaster and crisis research towards focusing on specific agents and specific events. thus, there is the inclination of social science researchers to say they studied this or that earthquake, flood, explosion and/or radioactive fallout. at one level that is nonsense. these terms refer to geophysical, climatological or physical happenings, which are hardly the province of social scientists. instead, those focused on the social in the broad sense of the term should be studying social phenomena. our view is that what should be looked at more is not the possible agent that might be involved, but the social setting of the happening. this becomes obvious when researchers have to look at such happenings as the southeast asia tsunami or locust infestations in africa. both of these occasions impacted a variety of social systems as well as involving social actors from outside those systems. this led in the tsunami disaster to sharp cultural clashes regarding on how to handle the dead between western european organizations who came into look mostly for bodies of their tourist citizens, and local groups who had different beliefs and values with respect to dead bodies (scanlon, personal communication with first author). the residents of the andaman islands lived at a level many would consider "primitive". at the time of the tsunami in southeast asia, they had no access to modern warning systems. but prior to the tsunami, members of the tribal communities saw signs of disturbed marine life and heard unusual agitated cries of sea birds. this was interpreted as a sign of impending danger, so that part of the population got off the beaches and retreated inland to the woods and survived intact (icpac report, ) . there is a need to look at both the current social settings as well as certain social trends that influence disasters and crises. in no way are we going to address all aspects of social systems and cultural frameworks or their social evolution, either past or prospective. instead, we will selectively discuss and illustrate a few dimensions that would seem to be particularly important with respect to crises and disasters. what might these be? let us first look at existing social structures around the world. what differences are there in authority relationships, social institutions and social diversity? as examples, we might note that australia and the united states are far more governmentally decentralized than france or japan (bosner, for example, rees ( ) , a cosmologist at cambridge university, gives civilization as we know it only a - chance of surviving the st century. schoff, ) . this affects what might or might not happen at times of disasters (it is often accepted that top-down systems have more problems in responding to crises and disasters). but what does it mean for the management of transboundary disruptions, which require increased cooperation between and across systems? will decentralized systems be able to produce "emergent" transboundary cooperation? as another example, mass media systems operate in rather different ways in china compared with western europe. this is important because to a considerable extent the mass communication system (including social media) is by far the major source of "information" about a disaster or a crisis. they play a major role in the social construction of disasters and crises. for a long time in the former soviet union, even major disasters and overt internal conflicts by way of riots were simply not openly reported (berg, ) . and only late in did chinese authorities announce that henceforth death tolls in natural disasters would be made public, but not for other kinds of crises (kahn, ) . another social structural dimension has to do with the range of social diversity in different systems (bolin & stanford, ) . social groupings and categories can be markedly different in their homogeneity or heterogeneity. the variation, for instance, can be in terms of life styles, class differences or demographic composition. the aging population in western europe and japan is in sharp contrast to the very young populations in most developing countries. this is important because the very young and the very old incur disproportionately the greatest number of fatalities in disasters. human societies also differ in terms of their cultural frameworks. as anthropologists have pointed out, they can have very different patterns of beliefs, norms, and values. as one example, there can be widely held different conceptions of what occasions disasters and crises. the source can be attributed to supernatural, natural, or human factors as indicated earlier. this can markedly affect everything from what mitigation measures might be considered to how recovery and reconstruction will be undertaken. norms indicating what course of action should be followed in different situations can vary tremendously. for example, the norm of helping others outside of one's own immediate group at times of disasters and crises ranges from full help to none. thus, although the kobe earthquake was an exception, any extensive volunteering in disasters was very rare in japan (for a comparison of the us and japan, see hayashi, ) . in societies with extreme cross-cultural ethnic or racial differences, volunteering to help others outside of one's own group at times of disasters or crisis is almost unknown. social structures and cultural frameworks of course are always changing. to understand future disasters and crises, it is necessary to identify and understand trends that may be operative with respect to both social structures and cultural frameworks. in particular, for our purposes, it is important to note trends that might be cutting across structural and cultural boundaries. globalization has been an ongoing force. leaving aside the substantive disputes about the meaning of the term, what is involved is at least the increasing appearance of new social actors at the global level. with respect to disaster relief and recovery, there is the continuing rise of transnational or international organizations such as un entities, the european union, religiously oriented groupings, and the world bank (boin et al., ) . with the decline of the importance of the nation state (guéhenno, ; mann, ) , more and new social actors, especially of an ngo nature, are to be anticipated. the rise of the information society has enabled the development of informal social networks that globally cut across political boundaries. this trend will likely increase in the future. such networks are creating social capital (in the social science sense) that will be increasingly important in dealing with disasters and crises. at the cultural level, we can note the greater insistence of citizens that they ought to be actively protected against disasters and crises (beck, ) . this is part of a democratic ideology that has spread around the world. that same ideology carries an inherent paradox: the global citizen may not appreciate government interference in everyday life, but expects government to show up immediately when acute adversity hits. finally, there has been the impact of the / attacks especially on official thinking not just in the united states but elsewhere also. this happening has clearly been a "focusing event" (as birkland, uses the term) and changed along some lines, certain values, beliefs and norms (smelser, ; tierney, ) . there is a tendency, at least in the us after / , to think that all future crises and disasters will be new forms of terrorism. one can see this in the creation of the us department of homeland security, which repeated errors in approach and thinking that over years of research have shown to be incorrect (e.g., an imposition of a command and control model, assuming that citizens will react inappropriately to warnings, seeing organizational improvisation as bad managing, see dynes, ) . these changes were accompanied by the downgrading of fema and its emphasis on mitigation (cohn, ) . valid or not, such ideas influence thinking about transboundary disasters and crises (and not just in the united states). the ideas expressed above and the examples used were intended to make several simple points. they suggest, for instance, that an earthquake of the same magnitude in france to one in iran will probably be reacted to differently. a riot in sweden will be a different phenomenon than one in myanmar. to understand and analyze such happenings requires taking into account the aspects just discussed. it is hard to believe that countries that currently have no functioning national government, such as somalia and the democratic republic of the congo or marginally operatives ones such as afghanistan, will have the same reaction to disasters and crises as societies with fully functional national governments. different kinds of disasters and crises will occur in rather different social settings. in fact, events that today are considered disasters or crises were not necessarily so viewed in the past. in noting these cross-societal and cross-cultural differences, we are not saying that there are no universal principles of disaster and crisis behavior. there is considerable research evidence supportive of this notion. we would argue, for example, that many aspects of effective warning systems, problems of bureaucracies in responding, the crucial importance of the family/household unit are roughly the same in all societies. to suggest the importance of cross-societal and cross-cultural differences is simply to suggest that good social science research needs to take differences into account while at the same time searching for universal principles about disasters and crises. this is consistent with those disaster researchers and scholars (e.g., oliver-smith, ) who have argued that studies in these areas have badly neglected the historical context of such happenings. of course, this neglect of the larger and particularly historical context has characterized much social science research of any kind (wallerstein, ) ; it is not peculiar to disaster and crisis studies. one trend that affects the character of modern crises and disasters is what we call the social amplifications of crises and disasters. pidgeon, kasperson, and slovic ( ) described a social augmentation process with respect to risk. to them, risk not only depends on the character of the dangerous agent itself but how it was seen in the larger context in which it appeared. the idea that there can be social amplification of risk rests on the assumption that aspects relevant to hazards interact with processes of a psychological, social, institutional, and cultural nature in such a manner that they can increase or decrease perceptions of risk (kasperson & kasperson, ) . it is important to note that the perceived risk could be raised or be diminished depending on the factors in the larger context, which makes it different from the vulnerability paradigm which tends to assume the factors involved will be primarily negative ones. we have taken this idea and extended it to the behaviors that appear in disasters and crises. extreme heat waves and massive blizzards are hardly new weather phenomena (burt, ) . there have recently been two heat waves, however, that have new elements in them. in , a long lasting and very intensive heat wave battered france. nearly , persons died (and perhaps , - , in all of europe). particularly noticeable was that the victims were primarily socially isolated older persons. another characteristic was that officials were very slow in accepting the fact that there was a problem and so there was very little initial response (lagadec, ) . there was a similar earlier happening in chicago not much noticed until reported in a study seven years later (see klinenberg, ) . it exhibited the same features, that is, older isolated victims, bureaucratic indifference, and mass media uncertainty. at the other temperature extreme, in , canada experienced an accumulation of snow and ice that went considerably beyond the typical. the ice storm heavily impacted electric and transport systems, especially around montreal. the critical infrastructures being affected created chain reactions that reached into banks and refineries. at least municipalities declared a state of emergency. such a very large geographic area was involved that many police were baffled that "there was no scene", no "ground zero" that could be the focus of attention (scanlon, ) . there were also many emergent groups and informal network linkages (scanlon, ) . in some ways, this was similar to what happened in august , when the highly interconnected eastern north american power grid started to fail when three transmission lines in the state of ohio came into contact with trees and short circuited (townsend & moss, ) . this created a cascade of power failures that resulted in blackouts in cities from new york to toronto and eventually left around million persons without power, which, in turn, disrupted everyday community and social routines (ballman, ) . it took months of investigation to establish the exact path of failure propagation through a huge, complex network. telecommunication and electrical infrastructures entwined in complex interconnected and network systems spread over a large geographic area with multiple end users. therefore, localized disruptions can cascade into large-scale failures (for more details, see townsend & moss, ) . such power blackouts have occurred among others in auckland, new zealand in (newlove, stern, & svedin, ) ; in buenos aires in (ullberg, ); in stockholm in and in siberian cities in (humphrey, ; in moscow in (arvedlund, ; in brazil in (brooks, ); in bangladesh in (al-mahmood, , and in sri lanka in (lbo, ). all of these cases initially involved accidents or software and hardware failures in complex technical systems that generate severe consequences creating a crisis with major economic and often political effects. these kinds of crises should have been expected. a national research council report ( ) forecast the almost certain probability of these kinds of risks in future network linkages. blackouts can also be deliberately created either for good or malevolent reasons having nothing to with problems in network linkages. employees of the now notorious enron energy company, in order to exploit western energy markets, indirectly but deliberately took off line a perfectly functioning las vegas power plant so that rolling blackouts hit plant-dependent northern and central california with about a million residences and businesses losing power (egan, ) . in the earliest days of electricity in new york city, the mayor ordered the power cut off when poor maintenance of exposed and open wires resulted in a number of electrocutions of citizens and electrical workers (jonnes, ) . one should not think of blackouts as solely the result of mechanical or physical failures creating chain-like cascades. most disasters are still traditional ones. for example, four major hurricanes hit the state of florida in . we saw very little in what we found that required thinking of them in some major new ways, or even in planning for or managing them. the problems, individual or organizational, that surfaced were the usual ones, and how to successfully handle them is fairly well known. more important, emergent difficulties were actually somewhat better handled than in the past, perhaps reflecting that officials may have had exposure to earlier studies and reports. thus, the warnings issued and the evacuations that took place were better than in the past. looting concerns were almost non-existent and less than ten percent indicated possible mental health effects. the pre-impact organizational mobilization and placement of resources beyond the community level was also better. the efficiency and effectiveness of local emergency management offices were markedly higher than in the past. not everything was done well. long known problematical aspects and failures to implement measures that research had suggested a long time ago were found. there were major difficulties in interorganizational coordination. the recovery period was plagued by the usual problems. even the failures that showed up in pre-impact mitigation efforts were known. the majority of contemporary disasters in the united states are still rather similar to most of the earlier ones. what could be seen in the hurricanes in florida was rather similar to what the disaster research center (drc) had studied there in the s and the s. as the electronic age goes beyond its birth and as other social trends continue, new elements may appear creating new problems that will necessitate new planning. if and when that happens, we may have rather new kinds of hurricane disasters, but movement in that direction will be slow. as the famous sociologist herbert blumer used to say in his class lectures a long time ago, it is sometimes useful to check whatever is theoretically proposed against personal experience. in , an extensive snowstorm led to the closing of almost all schools and government offices in the state of delaware. this was accompanied by the widespread cancellations of religious and sport events. there was across the board disruption of air, road and train services. all of this resulted in major economic losses in the millions of dollars. there were scattered interruptions of critical life systems. the governor issued a state of emergency declaration and the state as well as local emergency management offices fully mobilized. to be sure, what happened did not fully rival what surfaced in the canadian blizzard discussed earlier. but it would be difficult to argue that it did not meet criteria often used by many to categorize disasters. what happened was not that different from what others and we had experienced in the past. in short, it was a traditional disaster. finally, at the same time we were thinking about the florida hurricanes and the delaware snowstorm, we also observed other events that many would consider disasters or crises. certainly, a bp texas plant explosion in would qualify. it involved the third largest refinery in the country. more than a hundred were injured and persons died. in addition, there was major physical destruction of refinery equipment and nearby buildings were leveled. there was full mobilization of local emergency management personnel (franks, ) . at about the same time, there were landslides in the state of utah and california; a stampede with hundreds of deaths in a bombay, india temple, train and plane crashes in different places around the world, as well as large bus accidents; a dam rupture which swept away five villages, bridges and roads in pakistan; recurrent coal mine accidents and collapses in china; recurrent false reports in asia about tsunamis that greatly disrupted local routines; sinking of ferries with many deaths, and localized riots and hostage takings. at least based on press reports, it does not seem that there was anything distinctively new about these occasions. they seem to greatly resemble many such prior happenings. unless current social trends change very quickly in hypothetical directions (e.g., marked changes as a result of biotechnological advances), for the foreseeable future there will continue to be many traditional local community disasters and crises (such as localized floods and tornadoes, hostage takings or mass shootings, exploding tanker trucks or overturned trains, circumscribed landslides, disturbances if not riots at local sport venues, large plant fires, sudden discoveries of previously unknown very toxic local waste sites, most airplane crashes, stampedes and panic flights in buildings, etc.). mega-disasters and global crises will be rare in a numerical and relative sense, although they may generate much mass media attention. for example, the terrorist attacks in european cities (madrid in ; london in ; paris in ; brussels, nice, munich berlin in ; stockholm and manchester in ) were certainly major crises and symbolically very important, but numerically there are far more local train wrecks and car collisions everyday in many countries in the world. the more localized crises and disasters will continue to be the most numerous, despite the rise of transboundary crises and disasters. what are some of the implications for planning and managing that result from taking the perspective we have suggested about crises and disasters? if our descriptions and analyses of such happenings are valid, there would seem to be the need for new kinds of planning and preparation for the management of future crises and disasters (ansell et al., ) . non-traditional disasters and crises require some non-conventional processes and social arrangements. they demand innovative thinking "outside of the box" (boin & lagadec, ; lagadec, ) . this does not mean that everything has to be new. as said earlier, all disasters and crises share certain common dimensions or elements. for example, if early warning is possible at all, research has consistently shown that acceptable warnings have to come from a legitimately recognized source, have to be consistent, and have to indicate that the threat or risk is fairly immediate. these principles certainly pertain to the management of transboundary disruptions. actually, if traditional risks and hazards and their occasional manifestations were all we needed to be worried about, we would be in rather good shape. as already said several times, few threats actually manifest themselves in disasters. for example, in the , plus tornadoes appearing in the united states between and , there were casualties in only of them, and of these occasions accounted for almost half of the fatalities (noji, ) . similarly, it was noted in that while about . million people had been killed in earthquakes since , over % of them had died in only occurrences (jones, noji, smith, & wagner, , p. ) . we can say that risks and hazards and their relatively rare manifestations in crises and disasters are being coped with much better than they ever were even just a half-century ago. for example, there has been a remarkable reduction in certain societies of fatalities and even property destruction in some natural disaster occasions associated with hurricanes, floods and earthquakes (see scanlon, for data on north america). in the conflict area, the outcomes have been much more uneven, but even here, for example, the recurrence of world wars seems very unlikely. but transboundary crises and disasters require some type of transboundary cooperation. for example, let us assume that a health risk is involved. if international cooperation is needed, who talks with whom about what? at what time is action initiated? who takes the lead in organizing a response? what legal issues are involved (e.g., if health is the issue, can health authorities close airports?)? there might be many experts and much technical information around; if so, and they are not consistent, whose voice and ideas should be followed? what should be given priority? how could a forced quarantine be enforced? what of ethical issues? who should get limited vaccines? what should the mass media be told and by who and when? at a more general level of planning and managing, we can briefly indicate, almost in outline form, a half dozen principles that ought to be taken into account by disaster planners and crisis managers. first, a clear connection should be made between local planning and transboundary managing processes. there usually is a low correlation between planning and managing, even for traditional crises and disasters. but in newer kinds of disasters and crises, there are likely to be far more contingencies. planning processes need to be rethought and enhanced to help policymakers work across boundaries. second, the appearance of new emergent social phenomena (including groups and behaviors) needs to be taken into account. there are always new or emergent groups at times of major disasters and crises, but in transboundary events they appear at a much higher rate. networks and network links have to be particularly taken into account. third, there is the need to be imaginative and creative. the response to hurricane katrina suggests how hard it can be to meet transboundary challenges. but improvisation can go a long way. a good example is found in the immediate aftermath of / in new york. in spite the total loss of the new york city office of emergency management and its eoc facility, a completely new eoc was established elsewhere and started to operate very effectively within h after the attack. there had been no planning for such an event, yet around , persons were evacuated by water transportation from lower manhattan (kendra & wachtendorf, ; kendra, wachtendorf, & quarantelli, ) . fourth, exercises and simulations of disasters and crises must take into account transboundary contingencies. most such training and educational efforts along such lines are designed to be like scripts for plays. that is a very poor model to use. realistic contingencies, unknown to most of the players in the scenarios, force the thinking through of unconventional options. even more important, policymakers need to be explicitly trained in the management of transboundary crises and disasters. fifth, planning should be with citizens and their social groups, and not for them. there is no such thing as the "public" in the sense of some homogenous entity (blumer, ) . there are only individual citizens and the groups of which they are members. the perspective from the bottom up is crucial to getting things done. this has nothing to do with democratic ideologies; it has instead to do with getting effective and efficient planning and managing of disasters and crises. related to this is that openness with information rather than secrecy is mandatory. this runs against the norms of most bureaucracies and other organizations. the more information the mass media and citizens have, the better they will be able to react and respond. however, all this is easier said than done. finally, there is a need to start thinking of local communities in ways different than they have been traditionally viewed. up to now, communities have been seen as occupying some geographical space and existing in some chronological time. instead, we should visualize the kinds of communities that exist today are in cyberspace. these newer communities must be thought of as existing in social space and social time. viewed this way, the newer kinds of communities can be seen as very important in planning for and managing disasters and crises that cut across national boundaries. to think this way requires a moving away from the traditional view of communities in the past. this will not be easy given that the traditional community focus is strongly entrenched in most places around the world (see united nations, ) . but "virtual reality communities" will be the social realities in the future. assuming that what we have written has some validity, what new research should be undertaken in the future on the topic of future disasters and crises? in previous pages, we suggested some future studies on specific topics that would be worthwhile doing. however, in this section we want to outline research of a more general nature. for one, practically everything we discussed ought to be looked at in different cultures and societies. as mentioned earlier, there is a bias in our perspective that reflects our greater familiarity with and awareness of examples from the west (and even more narrowly western europe, the united states and canada). in particular, there is a need to undertake research in developing rather than only developed countries. and that includes at least some of these studies being undertaken by researchers and scholars from the very social systems that are being studied. the different cultural perspectives that would be brought to bear might be very enlightening, and enable us to see things that presently we do not see, being somewhat a prisoner of our own culture. second, here and there in this chapter, we have suggested that it is important to study the conditions that generate disasters and crises. but there has to be at least some understanding of the nature of x before there can be a serious turn to ascertaining the conditions that generate x. we have taken this first step in this chapter. future work should focus more on the generating conditions. a general model would involve the following ideas. the first is to look at social systems (societal, community and/or organizational ones), and to analyze how they have become more complex and tightly coupled. the last statement would be treated as a working hypothesis. if that turns out to be true, it could then be hypothesized that systems can break down in more ways than ever before. a secondary research thrust would be to see if systems also have developed ways to deal with or cope with threatening breakdowns. as such, it might be argued that what ensues is an uneven balance between resiliency and vulnerability. in studying contemporary trends, particular attention might be given to demographic ones. it would be difficult to find any country today where the population composition is not changing in some way. the increasing population density in high risk areas seems particularly important. another value in doing research on this topic is that much demographic data are of a quantitative nature. we mentioned financial and economic collapses cutting across different systems. how can financial collapse conceivably be thought of as comparable in any way to natural disasters and crises involving conflict? one simple answer is that for nearly a hundred years, one subfield of sociology has categorized, for example, panic flight in theater fires and financial panics as generic subtypes within the field of collective behavior (blumer, ; smelser, ) . both happenings involve new, emergent behaviors of a non-traditional nature. in this respect, scholars long ago put both types of behavior into the same category. although disaster and crisis researchers have not looked at financial collapses, maybe it is time that they did so. these kinds of happenings seem to occur very quickly, are ambiguous as to their consequences, cut across political and sector boundaries, involve a great deal of emergent behavior and cannot be handled at the community level. in short, what has to be looked for are genotypic characteristics not phenotypic ones (perry, ) . if whales, human beings, and bats can all be usefully categorized as mammals for scientific research purposes, maybe students of disasters should also pay less attention to phenotypic features. if so, should other disruptive phenomena like aids also be approached as disasters? our overall point, is that new research along the lines indicated might lead researchers to seeing phenomena in ways different than they had previously seen. finally, we have said little at all about the research methodologies that might be necessary to study transboundary ruptures. up to now, disaster and crisis researchers have argued that the methods they use in their research are indistinguishable from those used throughout the social sciences. the methods are simply applied under circumstances that are relatively unique (stallings, ) . in general, we agree with that position. but two questions can be raised. first, if social scientists venture into such areas as genetic engineering, cyberspace, robotics and complex infectious diseases, do they need to have knowledge of these phenomena to a degree that they presently do not have? this suggests the need for actual interdisciplinary research. social scientists ought to expand their knowledge base before venturing to study certain disasters and crises, especially the newer ones. there is something here that needs attention. in the sociology of science there have already been studies of how researchers from rather different disciplines studying one research question, interact with one another and what problems they have. researchers in the disaster and crisis area should look at these studies. our view is that the area of disasters and crises is changing. this might seem to be a very pessimistic outlook. that is not the case. there is reason to think, as we tried to document earlier, that human societies in the future will be able to cope with whatever new risks and hazards come into being. to be sure, given hazards and risks, there are bound to be disasters and crises. a risk free society has never existed and will never exist. but while this general principle is undoubtedly true, it is not so with reference to any particular or specific case. in fact, the great majority of potential 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authors: unceta, irene; nin, jordi; pujol, oriol title: differential replication in machine learning date: - - journal: nan doi: nan sha: doc_id: cord_uid: t ymc when deployed in the wild, machine learning models are usually confronted with data and requirements that constantly vary, either because of changes in the generating distribution or because external constraints change the environment where the model operates. to survive in such an ecosystem, machine learning models need to adapt to new conditions by evolving over time. the idea of model adaptability has been studied from different perspectives. in this paper, we propose a solution based on reusing the knowledge acquired by the already deployed machine learning models and leveraging it to train future generations. this is the idea behind differential replication of machine learning models. learning system's environment is prone to change in time. the gartner data science team survey [ ] found that over % of machine learning models developed in companies are never actually put into production, due mostly to a lack of alignment with environmental demands. to survive in such an ecosystem, machine learning models need to adapt to new conditions by learning to evolve over time. this notion of adaptability has been present in the literature since the early times of machine learning, as practitioners have had to devise ways in which to adapt theoretical proposals to their everyday life scenarios [ , , ] . as the discipline has evolved, so have the available techniques to this end. consider, for example, situations where the underlying data distribution changes resulting in a concept drift. traditional batch learners were incapable of adapting to such drifts. online learning algorithms were devised [ ] to succeed in this task by iteratively updating their knowledge according to the data shifts. in other situations, it is not the data that change but the business needs themselves. for instance, fraud detection algorithms [ ] are regularly retrained to incorporate new types of fraud. commercial machine learning applications are designed to answer very specific business objectives that may evolve in time. take, for example, the case where a company wants to focus on a new client portfolio. this may require evolving from a binary classification setting to a multi-class configuration [ ] . under such circumstances, the operational point of a trained classifier can be changed to adapt it to the new policy. alternatively, it is also possible to add patches in the form of wrappers to already deployed models. these endow models with new traits or functionalities that help them adapt to the new data conditions, either globally [ ] or locally [ ] . in contrast, when it is the very nature of the system that changes, alternatives are scarce. when change affects the entire ecosystem of a model, most existing solutions are not applicable. say, for example, that one of the original input attributes is no longer available, that a devised black-box solution is required to be interpretable or that updated software licenses require moving to a new production environment. it is such drastic changes in the demands of a machine learning system that this article is concerned with. a straightforward solution in this context is to discard the existing model and re-train a new one. however, by discarding the given solution, we loose all the acquired knowledge and have to rebuild and validate the full machine learning stack. this is seldom the most efficient not the most effective way for tackling this challenge. in this paper, we explore this problem and advocate for imitating the way in which biological systems adapt to changes. in particular, we stress the importance of reusing the knowledge acquired by the already existing machine learning model in order to train a second generation that is better adapted to th enew conditions. adaptation of machine learning models to new scenarios or domains is a well known problem in the machine learning literature. the most well known research branches are transfer learning and domain adaptation. domain adaptation usually deals with changes in the data distributions as time evolves, or with learning knowledge representations for one domain such that they can be transferred to another related target domain. for example, due to the covid- pandemic, several countries decided to accept card payments without introducing the pin up to euros instead of the previous euros limit, in order to minimize the interactions of card holders with the points of selling. this domain modification may affect to the fraud card detection algorithms, requiring modifications in their usage. conversely, transfer learning refers to the specific case where the knowledge acquired when solving one task is recycled to solve a different, yet related task [ ] . in general, the problem of transfer learning can be mathematically framed as follows. given source and target domains d s and d t and their corresponding tasks t s and t t , the goal of transfer learning is to build a target conditional distribution p (y t |x t ) in d t for task t t from the information obtained when learning d s and t s , where t s = t t and d s = d t . advantages of this kind of learning when compared with traditional learning are that learning is performed much faster, requiring less data, and even achieving better accuracy results. in this work we focus in a different adaptation problem. in our described scenario, the task remains the same but the existing solution is no longer fit because of changes in the environmental constraints. we can frame the problem at hand using the former notation as follows. given a domain d s , its corresponding task t , and the set of original environmental constraints c s that make the solution of this problem feasible we assume an scenario were a hypothesis space h s has been defined. in this context, we want to learn a new solution for the same task and for a new target scenario defined by the set of feasibility constraints c t , where c t = c s . this may or may not require the definition of a new hypothesis space h t . in a concise form and considering an optimization framework this can be rewritten as this problem corresponds to that of environmental adaptation. under this notation, the original solution corresponds to a model h s that belongs to the hypothesis space h s defined for the first scenario. this is a model that fulfills the constraints c s and maximizes p (y|x; h) for a training dataset s = {(x, y)}, defined by task the t on the domain d s . adaptation involves transitioning from this original scenario to scenario ii; a process which may be straightforward. although, in general, this is not the case. the solution obtained for the first scenario may be unfeasible in the second; thus, effectively ceasing the lifespan of the learned model. this happens when h s is outside of the feasible set defined by c t . in the most benevolent case, there may exist another solution from the original hypothesis space, h s , that fulfills the new constraints. however, there might be no overlapping between the set of constraints c t and the set of models defined by h s . this implies that no model of that hypothesis space can be considered a solution. in such cases, adaptation involves definition of a new hypothesis space h t altogether. take, for example, the case of an application with a multivariate gaussian kernel support vector machine. assume that due to changes in the existing regulation, models are required to be fully interpretable in the considered application. the new set of constraints is not compatible with the original scenario and hence we would require a complete change of substrate. in this scenario, we introduce the notion of differential replication of machine learning models as an efficient approach to ensure model survival in a new demanding environment, by building on knowledge acquired in previous generations. this is solving for scenario ii considering the solution obtained for scenario i. differential replications ensures the environmental adaptation of machine learning models when they are subjected to constant changes. "when copies are made with variation, and some variations are in some tiny way "better" (just better enough so that more copies of them get made in the next batch), this will lead inexorably to the ratcheting process of design solving the former environmental adaptation problem can sometimes be straightforwardly done by discarding the existing model and re-training a new one. this is possible when the new model hypothesis space h t is required to provide feasible solutions for the constraint set c t . however, it is worth considering the costs of this approach. in general, rebuilding a model from scratch (i) implies obtaining the clearance from legal, business, ethical, and engineering departments, (ii) does not guarantee that a good or better solution of the objective function will be achieved , (iii) requires a whole new iteration of the machine learning pipeline, which is costly and time-consuming, (iv) assumes full access to the training dataset, which may no longer be available or require a very complex version control process. plus, in many companies machine learning solutions are kept up-to-date using automated systems that continuously evaluate and retrain models; a technique known as continuous learning. note, however, that this may take huge storage space, due to the need to save all the new incoming information. hence, in the best case scenario, re-training is an expensive and difficult approach that assumes a certain level of knowledge that is not always guaranteed. nonetheless, this is the most commonly used technique for solving this environmental adaptation problem. in what follows we consider other techniques. environmental adaptation is well known for living beings. under the theory of natural selection, adaptation relies on changes in the phenotype of a species over several generations to guarantee its survival and evolution. this is sometimes referred to as differential reproduction. in the same lines, we define differential replication of a machine learning model as a cloning process in which traits are inherited from generation to generation while at the same time adding variations that make descendants more suitable/fit to the new environment. more formally, differential replication refers to the process of finding a solution h t that fulfills the constraints c t , i.e. it is a feasible solution, while preserving/inheriting features from h s . note that, in general, p (y|x; h t ) ∼ p (y|x; h s ). in the best case scenario, we would like to preserve or improve the performance of the source solution h s , also known as the parent. however, this is requirement that may not always be achieved. in a biological simile, requiring a guepard to be able to fly may imply loosing its ability to run fast. in this section, we consider existing approaches to implement differential replication in its attempt to solve the problem of environmental adaptation. the notion of differential replication is built on top of two concepts. first, there is some inheritance mechanism that is able to transfer key aspects from the previous generation to the next. that would account for the name of replication. second, the next generation should display new features or traits not present in their parents. this corresponds to the idea of differential. these new traits should make the new generation more fit to current environment to enable environmental adaptation of the offspring. particularizing to machine learning models, implementing the concept of differential may involve a fundamental change in the substratum of the given model. this means we need a new hypothesis space that will ensure that part of the models in that space fulfill the constraints of the new environment c t . consider, for example, the case of a large ensemble of classifiers. in highly time demanding tasks, this model may be too slow to provide real time prediction when deployed into production. differential replication of this model enables moving from this architecture to a simpler, more efficient one, such as that of a shallow neural network [ ] . this "child" network can inherit the decision behavior of its predecessor while at the same time being more fit to the new environment. conversely, replication requires that some behavioral aspect be inherited by the next generation. usually, it is the model's decision behavior that is inherited, so that the next generation will replicate the parent decision boundary. replication can be attained in many different ways. as shown in fig. , depending on the amount of knowledge that is assumed about the initial data and model, mechanisms for inheritance can be categorized as follows: • inheritance by sharing the dataset: two models trained on the same data are bound to learn similar decision boundaries. this is the weakest form of inheritance possible, were no actual information is transferred from source to target. here the decision boundary is reproduced indirectly and mediated through the data themselves. re-training falls under this category. this form of inheritance requires no access to the parent model, but assumes knowledge of its training data. • inheritance using edited data: editing is the methodology that allows data selection for training purposes [ , , ] . editing can be used to preserve those data that are relevant to the decision boundary learned by the original solution and use them to train the next generation. take, for example, the case where the source hypothesis space corresponds to the family of support vector machines. in training a differential replica, one could retain only those data points that were identified as support vectors. this mechanism assumes full access to the model internals, as well as to the training data. • inheritance using model driven enriched data: data enrichment is a form of adding new information to the training dataset through either the features or the labels. in this scenario, each data sample in the original training set is augmented using information from the parent decision behavior. for example, a sample can be enriched by adding additional features using the prediction results of a set of classifiers. alternatively, if instead of learning hard targets one considers using the output of the parent's class probability outputs or logits as soft-targets, this richer information can be exploited to build a new generation that is closer in behavior to the parent. under this category fall methods like model distillation [ , , , ] , as well as techniques such as label regularization [ , ] and label refinery [ ] . in general, this form of inheritance requires access to the source model and is performed under the assumption of full knowledge of the training data. • inheritance by enriched data synthesis a similar scenario is that where the original training data is not accessible, but the model internals are open for inspection. in this situation, the use of synthetic datasets has been explored [ , ] . in some cases, intermediate information about the representations learned by the source model are also used as a training set for the next generation. this form of inheritance can be understood as a zero-shot distillation [ ] . • inheritance of internals model's knowledge: in some cases, it is possible to access the internal representations of the parent model, so that more explicit knowledge can be used to build the next generation [ , ] . for example, if both parent and child are neural networks, one can force the mid-layer representations to be shared among them [ ] . alternatively, one could use the second level rules of a decision tree to guide the next generation of rule-based decision models. • inheritance by copying in highly regulated environments, access to the original training samples or to the model internals is not possible. in this context, experience can also be transmitted from one model to its differential replica using synthetic data points labelled according to the hard predictions of the source model. this has been referred to as copying [ ] . note that on top of a certain level of knowledge about either the data or the model, or both, some of the techniques listed above often impose also additional restrictions on the considered scenarios. techniques such as distillation, for example, assume that the original model can be controlled by the data practitioner, i.e. internals of the model can be tuned to force specific representations of the given input throughout the adaptation process. in certain environments this may be possible, but generally it is not. to illustrate the utility of differential replication, we describe six different scenarios where it can be exploited to ensure a devised machine learning solution adapts to different changes in its environment. a widely established technique to provide explanations is to use linear models, such as logistic regression. model parameters, i.e. the linear coefficients associated to the different attributes, can be exploited to provide explanations to different audiences. although this approach works in simple scenarios where the variables do not need to be modified nor pre-processed, this is never the case for real life applications, where variables are usually redesigned before training and new more complex features are often introduced. this is even worse when, in order to improve model performance, data scientists create a large set of new variables, such as bi-variate ratios or logarithm scaled variables, to capture non-linear relations between original attributes that linear models cannot handle during the training phase. this results in new variables being obfuscated and therefore often not intelligible for humans. a straightforward solution using differential replication is to replace the whole predictive system, composed by both the pre-processing/feature engineering step and the machine learning model by a copy that considers both steps as a single black box model [ ] . doing this, we are able to deobfuscate model variables by training copies to learn the decision outputs of trained models directly from the raw data attributes without any pre-process. in-company infrastructure is subject to continuous updates due to the rapid pace with which new software versions are released to the market. changes in the organizational structure of a company may drive the engineering department to change course. say, for example, that a company whose products were originally based on google's tensorflow package [ ] makes the strategic decision of moving to pytorch [ ] . in doing so, they might decide to re-train all models from scratch in the new environment. this is a long and costly process that can even result in a loss of performance. specially if original data is not available or the in-house data scientist are new to this framework. alternatively, using differential replication, the knowledge acquired by the existing solutions could be exploited in the form of hard or soft labels or as additional data attributes for the new generation. as a model is tested against new data throughout its lifespan, some of its learned biases may be made apparent. under such circumstances, one may wish to transit to a new model that inherits the original predictive performance but which ensures non-discriminatory outputs. a possible option is to edit the sensitive attributes to remove any bias, reducing in this way the disparate impact in the task t , and then training a new model on the edited dataset. alternatively, in very specific scenarios where the sensitive information is not leaked through additional features, it is possible to build a copy by removing the protected data variables [ ] . or even, redesign the hypothesis space considering a loss function to account for the fairness dimension when training subsequent generations. batch machine learning models are rendered obsolete by their inability to adapt to a change in the data distribution. when this happens the most straightforward solution is to wait until there are enough samples of the new distribution and re-train the model. however, this solution is timely and often expensive. a faster solution is to use the idea of differential replication to create a new enriched dataset able to detect the data drift. for example, including the soft targets and a timestamp attribute in the target domain, d t . then, train a new model using this enriched dataset that replicates the decision behavior of the previously trained classifier. finally, we also need to allow the new model to accept new incoming data samples to be learned. this second characteristic can be added by incorporating the online requirement in the c t constrains for the differential replication process [ ] . developing good machine learning models requires abundant data. the more accessible the data, the more effective a model will be. in real applications, training machine learning models usually requires collecting a large volume of data from users, often including sensitive information. directly releasing these models trained using user data could derive in privacy breaches, as the risk of leaking sensitive information encoded in the public model increases. differential replication can be used to avoid this issue by is training another model, usually a simpler one, that replicates the learned decision behavior but which preserves the privacy of the original training set by not being directly linked to these data. the use of distillation techniques in the context of teacher-student networks, for example, has been reported to be successful in this task [ , ] . auditing machine learning models is not an easy task. when an auditor wants to audit several models under the same constraints, it is required that all models audited fulfill an equivalent set of requirements. those requirements may limit the use of certain software libraries, or of certain model architectures. usually, even within the same company, each model is designed and trained on its own basis. as research in machine learning grows, new models are continuously devised. however, this fast growth in available techniques hinders the possibility of having a deep understanding of those models and makes the assessment of some auditing dimensions a nearly impossible task. in this scenario, differential replication can be used to establish a small set of canonical models into which all others can be translated. in this sense, deep knowledge of these set of canonical models would be enough to drive auditing tests. for example, let us consider that the canonical model is a deep learning architecture with a certain configuration. any other model can be translated into this particular architecture using differential replication . the auditing process need then only consider how to probe the canonical deep network to report impact assessment. in this paper we have described a general framework based on knowledge reuse from generation to generation to extend the useful life of machine learning models by adapting them to their changing environment. to tackle this issue of environmental adaptation, we have proposed a mechanism inspired in how biological organisms evolve: differential replication. differential replication allows machine learning models to modify their behavior to meet the new requirements defined by the environment. we envision this replication mechanism as a projection operator able to translate the decision behavior of a machine learning model into a new hypothesis space with different characteristics. this allows traits of a given classifier to be inherited by another, more suitable under the new premises. we have listed different inheritance mechanisms to achieve this goal, depending on specific knowledge availability scenarios. these range from the more permissive inheritance by sharing the dataset to the more restrictive inheritance by copying, which is the solution requiring less knowledge about the parent model and training data. finally, we provide examples of how differential replication applies in practice for six different real-life scenarios. on the origin of species by means of natural selection, or preservation of favoured races in the struggle for life magic quadrant for data science and machine learning platforms engaging the ethics of data science in practice fairer machine learning in the real world: mitigating discrimination without collecting sensitive data the fallacy of inscrutability large scale online learning end-to-end neural network architecture for fraud scoring in card payments online error-correcting output codes uncertainty estimation for black-box classification models: a use case for sentiment analysis why should i trust you?: explaining the predictions of any classifier a survey on transfer learning model compression application of proximity graphs to editing nearest neighbor decision rule geometric decision rules for instance-based learning algorithms application of the gabriel graph to instance based learning distilling the knowledge in a neural network rethinking the inception architecture for computer vision knowledge distillation in generations: more tolerant teachers educate better students when does label smoothing help revisiting knowledge distillation via label smoothing regularization label refinery: improving imagenet classification through label progression using a neural network to approximate an ensemble of classifiers zero-shot knowledge distillation in deep networks knowledge distillation from internal representations explaining knowledge distillation by quantifying the knowledge transactional compatible representations for high value client identification: a financial case study copying machine learning classifiers towards global explanations for credit risk scoring tensorflow: a system for large-scale machine learning automatic differentiation in pytorch using copies to remove sensitive data: a case study on fair superhero alignment prediction from batch to online learning using copies patient-driven privacy control through generalized distillation private model compression via knowledge distillation this work has been partially funded by the spanish project pid - gb-i (mineco/feder, ue), and by agaur of the generalitat de catalunya through the industrial phd grant -di- . key: cord- - cpe x authors: moustakas, aristides title: ranking the explanatory power of factors associated with worldwide new covid- cases date: - - journal: nan doi: nan sha: doc_id: cord_uid: cpe x disease spread is a complex phenomenon requiring an interdisciplinary approach. covid- exhibited a global spatial spread in a very short time frame resulting in a global pandemic. data of new covid- cases per million were analysed worldwide at the spatial scale of a country and time replicated from the end of december to late may . data driven analysis of epidemiological, economic, public health, and governmental intervention variables was performed in order to select the optimal variables in explaining new covid- cases across all countries in time. sequentially, hierarchical variance partitioning of the optimal variables was performed in order to quantify the independent contribution of each variable in the total variance of new covid- cases per million. results indicated that from the variables available new tests per thousand explained the vast majority of the total variance in new cases ( . %) followed by the governmental stringency index ( . %). availability of hospital beds per k inhabitants explained % extreme poverty explained . %, hand washing facilities . %, the fraction of the population aged or older explained . %, and other disease prevalence (cardiovascular diseases plus diabetes) explained . %. the percentage of smokers within the population explained . % of the total variance, while population density explained . %. patterns of infectious diseases across spatial and temporal scales are fundamental for understanding their dynamics and for designing eradication strategies [ , ] . disease spread is a complex phenomenon and requires an interdisciplinary approach spanning from medicine to statistics and social sciences [ ] . covid- exhibited a global spatial spread in a relatively very short time frame resulting in being characterized as a pandemic by the world health organisation [ ] . to date there is no known anti-viral treatment or vaccine against covid- [ ] . therefore the available options against the virus are the characteristics of the immune system and health status of each individual, the health system of the country that the individual has access to, the social behaviour of the other individuals forming the society, public interventions of movement or public campaigns, and testing [ ] [ ] [ ] . thus, there are relatively few options to be employed in order to diminish the spread of the disease. this scarcity of options makes quantifying the factors associated with disease spread more important and ranking the relative contribution of each factor on covid- spread may facilitate diminishing it [ ] . analysis so far has often been dominated either on a one-at-a-time factor analysis (e.g. new cases per testing effort or total cases per age structure) or on a country basis analysis (e.g doubling time in one country in comparison to other countries). while such comparisons are straightforward and comprehensive, from a statistical perspective they are examining one factor at a time and masking underlying characteristics within countries under a variable 'country' [ ] . this results in a hidden burden of the underlying factors regarding disease spread and causality is often discussed in a speculative manner. admittedly the problem is complex due to the large differences across the potential underlying factors across countries. a small variance implies that the mean contains virtually all of the information, while a large variance implies that more information than the mean is present [ ] . when examining several countries together and across time, quantifying the variance may be more informative than the mean [ ] . variance is introduced both by space, there are large e.g. climatic differences between locations on the same date, as well as by temporal e.g. climatic or behavioural changes within locations in seasons [ ] [ ] [ ] . the potential effect of economic, epidemiological and public health, or governmental interventions may become clearer when the contribution of these factors into new covid- cases are analysed accounting for the fact that they derive from different countries as well as in different time snapshots [ ] but in a way that the effect of each factor can be quantified in conjunction with the effects of other factors. to that end methods that can account for both spatial and temporal autocorrelation [ ] in the data of new covid- cases but can quantify the effect of each epidemiological, economic, public health, and governmental intervention are key to our understanding of how the disease spreads in populations worldwide [ , ] . in this study spatio-temporal worldwide data of new covid- cases form the "our world in data" database [ ] were analyzed using computational statistics. the spatial replicate of the dataset included over countries time replicated for each country across a period of ≈five months. data driven analysis was performed in order to quantify the optimal variables in cases where several candidate variables were available. during the data driven variable selection, the fact that data derived from different countries and were time replicated was accounted for by nesting the variance of time within the variance of country and treated as random effects [ , ] . the percentage of the total variance explained by each epidemiological, economic, public health, and governmental intervention variables associated with covid- new cases was quantified using hierarchical variance partitioning [ , ] thereby ranking the relative contribution of the variance of each factor on new covid- cases worldwide. the objective was to quantify epidemiological, public health, economic, and governmental intervention factors associated with covid- spread worldwide. new covid- cases per million per country per time step were used a proxy of disease spread. new cases per million in each country was chosen instead of new cases per country as this estimator is less biased by the total population of each country -countries with higher populations are more likely to produce higher new cases or total but the number may be relatively low in comparison to the total population pool. data regarding new covid- cases per million from the "our world in data" database were analyzed. the dataset was last accessed on / / and the download location is https://github.com/owid/covid- data/tree/master/public/data. the data derive from the european centre for disease prevention and control (ecdc), an eu agency with the aim to strengthen europe's defense against infectious diseases. the ecdc collects and aggregates data from countries around the world. the most up-to-date data for any particular country is therefore typically available earlier via the national health agencies than via the ecdc. this lag between nationally available data and the ecdc data is not very long as the ecdc publishes new data daily; typically this time lag is at the level of some hours and less than a day. the ecdc collects compiles and harmonizes data from around the world in a consistent way which allows us to compare what is happening in different countries. the spatial replicate of the dataset comprised of countries while the temporal replicate spans from / / to (including) / / . the variables included: from the available variables male and female smokers were averaged as 'smokers'. we employed generalised linear mixed effects models (lme; [ ] ) with new covid- cases per million as the dependent variable. as the dataset contained several potential indexes of testing, population density, or age structure within each country, initial analysis was conducted in order to select the most informative index of each. we initially sought to quantify the most parsimonious data driven index of testing which included the fixed effects of (i) news tests (ii) total tests (iii) new tests per thousand (iv) total tests per thousand (v) new tests smoothed, (vi) new tests smoothed per thousand. this was achieved by fitting six lmes with new cases per million as the dependent variable and six lmes with i -vi as the single independent variable. the random effect structure of each lme included the nested variance of time within each country (random~country/time). doing so the fitted lmes accounted for both temporal and spatial autocorrelation in the time replicated data deriving from different geographic locations [ , ] . lmes were fitted with maximum likelihood (ml) estimation to allow comparisons between models with different fixed effects and selecting the lme that exhibited the lowest akaike (aic) value [ , ] . here and throughout the analysis, there were , data points in the analysis but there were variables with missing values at some time steps or at some countries. missing values were omitted from the statistical analysis. therefore aic values are compared between models fitted with different fixed effects but also with potentially different sample sizes. similarly, lmes with new cases per million as the dependent variable and the fixed effects of (i) population or (ii) population density, and the nested random effects of time within country were fitted with ml and compared against aic values to select the optimal data driven population index. regarding age structure of the population within each country, the available variables were (i) median age of the population, (ii) the percentage of the population aged or older, and (iii) the percentage of the population aged or older. the analysis proceeded by selecting the ml fitted lme with the lowest aic between the three available age population structure variables. all three fitted lmes contained the random effects of time nested within country. regarding economic status of the population within each country, the available variables were (i) gdp per capita, and (ii) percentage of the population under extreme poverty. the analysis proceeded by selecting the ml fitted lme with the lowest aic between the two available economy status variables. the two fitted lmes contained the random effects of time nested within country. having selected the optimal index of testing, population density and age structures the analysis proceeded with the following variables: ( ) population density, ( ) new tests per thousand, ( ) governmental stringency index, ( ) percentage of the population aged > , ( ) percentage of the population under extreme poverty, ( ) cvd death rate, ( ) diabetes prevalence, ( ) percentage of smokers, ( ) percentage of the population with access to hand washing facilities, and ( ) hospital beds per k inhabitants within each country as independent variables. hierarchical variance partitioning (hvp) statistical modelling was implemented to account for the contribution of each data driven epidemiological, economic, public health, and governmental intervention explanatory variable to the total variance of new covid- per million cases [ , ] . hvp is a statistical framework that is capable of handling correlated independent variables, whilst providing a reliable ranking of predictor importance of each variable [ ] . variance partitioning is calculated from the akaike (aic) weights of each explanatory variable and it is based upon the number of times that a variable was significant in all possible combinations of the explanatory variables. the hvp function produces a minor rounding error for hierarchies constructed from more than nine variables [ ] -the available data driven variables were . to check if this error affects the inference from an analysis, the analysis was repeated several times with the variables entered in a different order [ ] . the analysis resulted in changes in the derived results when the order of the variables was changed. the analysis proceeded by creating a new variable that merged together other disease related variables: other diseases variable= (cvd_death_rate + diabetes_prevalence) plus the other remaining eight variables resulting in a total of nine variables. there is no known statistical bias in hvp when or fewer variables are used [ ] . the optimal data driven index for explaining new cases per million from the ones available regarding testing was new cases per thousand as fitted by lmes and selected against the lowest aic value (table a) . new tests per thousand smoothed could not be fitted as the lme did not converge (table a) . the optimal data driven population index for new cases per million was population density (table b ). the optimal data driven index for age structure within the population was the percentage of the population within each country aged or older (table c ). the optimal aic selected lme regarding the economic status of the population within each country in relation to new covid- cases per million was extreme poverty (table d) . results from hvp indicated that total tests per thousand explained . % of the total variance of new cases per million, while governmental stringency index explained . % (fig. , table ). availability of hospital bed per k inhabitants explained % (fig. , table ). extreme poverty explained . % of the total variance of new cases per million, hand washing facilities . %, the fraction of the population aged or older explained . %, other disease prevalence (cardiovascular diseases plus diabetes) explained . % (fig. , table ). the percentage of smokers within the population explained . % of the total variance of new covid- cases per million, while population density explained . % (fig. , table ). the best model fit regarding new covid- cases per million and the economic status of the country where the new cases are recorded indicated that extreme poverty was a better predictor of new cases than gdp per capita. it is thus the poorest individuals within each country impacted rather than poor countries. from the data available, the fraction of the population aged or older explained optimally new cases per million and not median population age. total tests per thousand and not new tests or new tests smoothed or other available indexes is a better predictor of new cases per million, perhaps unsurprisingly as the number of new cases is already normalized by the population and thus the number of tests also normalized by the population explains better the pattern. the latter also applies for population density instead of total population as the best available predictor of new cases per million. summing up, from the data-driven analysis it is evident that new covid- cases per million are best explained by extreme poverty prevalence within each country as well as by the fraction of the population older than , thereby indicating association of the spread of the disease with the poor and older. results from variance partitioning of the data-driven selected epidemiological, public health, economic, and governmental intervention variables explaining covid- new cases per million across countries through time, indicated that the vast majority of new cases per million are explained by the number of tests conducted. the number of new tests per thousand explains over % of the total variance through time and countries and thus the message regarding the efficacy of testing against covid- spread is strong, at least form the results derived here. the efficacy of testing has been highlighted as the best strategy against other diseases too across humans, agriculture, and wildlife [ , , , ] . it therefore seems that the optimal strategies against covid- spread should include high number of tests both to suspicious cases as well as random population testing. would increasing the number of tests result in detecting more covid- cases? lost covid- cases are not uncommon [ , ] . from a statistical perspective, variance partitioning does not provide information on the sign of the effects (positive or negative) it simply shows in how many cases this variable could not be excluded from the final optimal statistical model in explaining new covid- cases. the slope between new tests per thousand inhabitants and new cases per million vary between countries (fig. a) . indeed there are countries where the slope between new cases per million and new tests per thousand are positive indicating that testing more would actually result into identifying more cases (fig. a) ; [ ] . however, there are also countries with a negative slope between new tests -new cases' indicating that testing frequency is saturated (fig. a) . overall, using data from all countries and time steps, the relationship between testing and new cases is positive indicating that worldwide more tests would result in identifying higher number of new cases (fig. b) . therefore the efficacy of testing has not been saturated. the second best variable in explaining new covid- cases per million was the governmental stringency index. the governmental stringency index contains several measures taken by governments including school closures, national and international movement restrictions, public gathering and public events restrictions, exiting home restrictions as well as testing policies and financial measures [ ] . to that end testing policy is in part contained in the stringency index as a weighted percentage of the overall index. however the relationship between stringency index and new tests per thousand is very weak with both r and slope close to zero: linear regression (new_tests_per_thousand) = . + . (stringency_index), s = . , r = . %, p< . . therefore of the available governmental measures summarized in the stringency index, testing frequency can be treated independently. in general, countries increased their level of stringency as their number of confirmed covid- cases raised, however there is significant variation in the rate and timing of this relationship [ ] . another study indicated that in the early and accelerating stages of the pandemic, many citizens across countries viewed their governments' response as insufficient [ ] . in general the status of the infection spread and policy implementation influence restrictions uniformly across every countries [ ] . given the overall large effect of testing on new cases, it has been investigated whether there exists a testing frequency for covid- such that the shutdown could have been avoided [ ] . the study concluded that indeed there is an optimal testing frequency such that lockdown and thus governmental stringency may not be deemed necessary [ ] . the test against covid- is known to be imperfect but not precisely known [ ] and testing strategies to surmount this problem have been proposed [ ] . the availability of hospital beds per k inhabitants, hand washing facilities, the effect of covid- in the older people as well as prevalence of other diseases and smokers have been highlighted [ , , ] and this study confirms their importance. environmental factors have also been reported to play an important role in covid- dynamics [ ] however this study did not explore their relative contribution. table . data driven variable selection in cases where several candidate variables were available. variable selection was conducted by fitting lmes with new covid- cases per million as dependent variable and the candidate explanatory variables as single fixed effect variables and the variance introduced time nested within the variance of countries as random effects. models were fitted with ml to allow comparisons between 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species of vertebrates, especially mammals, have been successful invaders and colonizers of new territories, in particular, insular island ecosystems. others have exhibited high environmental tolerance and adaptability after careful and repeated introductions to new locales by humans. following establishment, several vertebrate species have become important pests. these pests harm agricultural systems by damaging agricultural lands [e.g., rabbits (oryctolagus cuniculus linnaeus) in australia and new zealand], by attacking crops [e.g., european starlings (sturnus vulgaris linnaeus) in the united states], and by acting as sources for communicable diseases [e.g., brushtail possums, (trichosurus vulpecula kerr) , are reservoirs for bovine tuberculosis (mycobacterium bovis karlson and lessel) in new zealand]. other pest vertebrates damage natural systems by threatening the continued existence of endangered flora [e.g., goats (capra hircus linnaeus) on the galapagos islands] and fauna [e.g., brown tree snake (boiga irregularis { merrem }) on guam], and by adversely affecting wilderness areas by changing ecosystem functions and diversity (vitousek et al., ) . the continued relocation of vertebrates exacerbates the ongoing problem of global homogenization of biota (lodge, ) . movement of particular vertebrates into areas where they had not previously existed has, in some instances, occurred naturally without human intervention [e.g., the passerine bird (zosterops lateralis { latham }) arrived in new zealand unassisted from australia]. the vast majority of vertebrate translocations have been human assisted. accidental introduction has occurred as a consequence of human transportation [e.g., brown tree snakes, mice (mus musculus lin-naeus) , and rats such as rattus rattus linnaeus and r. norvegicus berkenhout) ]. some releases have been intentional (but illegal) to serve self-centered private interests [e.g., monk parakeets (myiopsitta monachus { boddaert }) in new york, florida, and texas]. other species have been legitimately introduced to procure public benefit by providing: ( ) new agricultural products [e.g., european wild boars (sus scrofa linnaeus); sheep (ovis aries linnaeus); cows (bos taurus linnaeus), goats and rabbits for meat, and brushtail possums for fur in new zealand], ( ) recreation [e.g., red deer (cervus elaphus linnaeus), fallow deer (dama dama linnaeus), and trout (salmo trutta linnaeus and s. gairdneri richardson) in new zealand]; ( ) companionship [e.g., cats (felis domesticus linnaeus) and dogs (canis familiaris linnaeus)]; or ( ) biological control agents [e.g., the european fox (vulpes vulpes linnaeus), stoats (mustela erminea linnaeus), weasels (m. nivalis linnaeus) , and ferrets (m. putorius furo linnaeus) for the control of rabbits in australia or new zealand; cane toads chemical and cultural control of vertebrate pests is expensive and nonsustainable, and at best provides a temporary local solution to problems (hone, ; williams & moore, ) . biological control of vertebrates, a potentially less expensive and self-sustaining method of population suppression, has focused primarily on mammalian pests. predators, parasites, and pathogens specific to mammals with two notable exceptions (the myxoma and calici viruses that infect rabbits) have failed to provide satisfac-tory control (shelford, ; howard, ; davis et al., ; wood, ; smith & remington, ; whisson, ) . historical records indicate that the majority of attempts at vertebrate biological control have been ad hoc efforts and not the product of careful studies designed to elucidate factors and conditions likely to affect the impact of natural enemy introductions on pest populations. furthermore, failure of biological control of vertebrates by predatory vertebrates has compounded problems associated with exotic vertebrates because control attempts result in addition of new species that cause biological and conservation problems. the level of control achieved by natural enemies is dependent on ratios of natality to mortality of control agents and their host species (davis et al., ) . for vertebrates these ratios are affected by many factors: advanced learning; social, territorial, and breeding behaviors; chemical, physical, and immunological defenses; temporal and spatial escape strategies; and genetic selection in both natural enemy and host populations for persistent coexistence. these complex interrelated factors, coupled with opportunistic feeding habits, have made vertebrate pests difficult targets for biological control with natural enemies. advances in understanding of mammalian fertilization biology have provided molecular biologists with necessary information to develop and investigate the concept of immunocontraception for vertebrate pest control. immunocontraception utilizes genetically modified pathogens that express surface proteins from the target pest's egg or sperm to induce an immune response in the host. antibodies then attack gametes in the host's reproductive tract causing sterilization (tyndale-biscoe, b . computer models indicate that immunocontraception may provide long-term control of vertebrate pests because genetically modified pathogens reduce net reproductive rates without killing hosts (barlow, (barlow, , . in this chapter, i discuss attributes that have aided vertebrate establishment; damage resulting from colonization and uncontrolled population growth; biological control of mammalian pest species with predators, parasites, and pathogens; and future directions that biological control research for vertebrates is taking with genetically engineered microorganisms. permissive to successful introductions of new species. e ton's ( ) predictions have been substantiated in part by paleobiological reconstructions of invasions between newly joined communities (vermeiji, ) and by mathematical modeling describing multi-species interactions in communities (macarthur, ; case, ) . isolated oceanic islands (e.g., new zealand), and insular continents and habitats (e.g., australia and lakes) often have a low diversity of native species. such environments have typically experienced little immigration and are susceptible to invasion by vertebrates (brown, ) . stable, speciose communities with high levels of interspecific competition appear to resist invasion by new species and are sources of successful colonists into less speciose or disturbed communities (macarthur, ; brown, ; lodge ) . this phenomenon has produced asymmetrical patterns of colonization, with successful vertebrate invaders usually being native to continents or extensive nonisolated habitats within continents with more diverse biotas (brown, ; vermeiji, ) . continental herbivores and predators have been very successful in establishing self-sustaining populations in insular habitats, in part because such habitats often lack large generalist vertebrates and essentially have just two trophic levels, producers and decomposers (if specialist herbivores and their predators are excluded) (vitousek, ) . niches equivalent to those on the mainland are largely unoccupied (brown, ) . insular ecosystems therefore often appear to readily accommodate generalist herbivores and predators, perhaps because of low levels of competition for resources that are often inadequately defended chemically or physically (vitousek, ; vermeij, ; bowen & van vuren, ) . organisms from insular habitats that have not coevolved closely with predators or herbivores lack life history features that deter attack or permit survival despite high mortality from predation or herbivory (bowen & van vuren, ) . lack of such biological attributes may increase the competitive advantage of exotics (case, ; coblentz, ; vitousek, ) . introduced vertebrates can also be extremely disruptive in continental regions when habitat disturbance by urbanization or agriculture occurs. european wild boars have detrimental effects on gray beech forests in the great smoky mountains in the southeast united states. habitat disturbance-through pig rooting, trampling, and browsing-and human removal of predators (pumas and wolves) aided pig establishment and spread in this area (bratton, ; singer et al., ; vitousek, ) . communities vary in their ability to accommodate the establishment and proliferation of new species (primack, ) . elton ( ) suggested that species-poor communities (e.g., islands) or highly disturbed habitats are more although there are well-recognized exceptions to general rules that characterize successful vertebrate colonists (ehrlick, ; williamson & fitter, b) , species that establish self-sustaining populations outside their native range typically exhibit some of the following general characters: ( ) short generation times, ( ) high dispersal rates, ( ) high tolerance for varying geographic and climatic conditions, ( )polyphagy, ( ) low attack rates from upper trophic level organisms, and ( ) human commensalism (ehrlich, (ehrlich, , lodge, ; williamson & fitter, a) . the assumption of a high intrinsic rate of increase is generally unnecessary for establishment (ehrlich, ; lodge, ) , although it is important for the establishment of some exotic bird species (veltman et al., ) . the spread of the european rabbit in australia and new zealand, countries that both historically lacked significant eutherian mammal fauna, illustrates some of the preceding points. the european rabbit originated in spain and portugal (corbet, ) and spread through most of europe over years ago following deforestation by humans for agriculture and overgrazing by livestock. animals reared in captivity were carried through europe in advance of naturally spreading populations (flux, ) . the spread of the european rabbit throughout australia following its introduction in varied from km/year to approximately km/year. rate of spread was fastest across dry savannas where conditions were most similar to mediterranean climates and slowest through woodlands (myers et al., ) . in australia, habitat alteration by humans such as conversion of land to pasture, overgrazing of rangelands, and predator eradication [e.g., dingos (canis familiaris dingo meyer)] aided rabbit survivorship and spread. rabbits are polyphagous and feed on grasses and browse shrubs. during severe food and water shortages, bark, fallen leaves, seed pods, tree roots, and termites are consumed (myers et al., ) . rabbits are highly fecund and exhibit rapid population growth under good conditions. individual female rabbits to months of age can produce litters averaging to young, and with abundant food to offspring per year are produced (gibb & williams, ) . behavioral adaptability, sociality, and territoriality, in addition to use of elaborate underground warrens, have also aided rabbit proliferation in marginal habitats (myers et al., ) . assistance in establishment some of the first introductions of exotic vertebrates were those commensal with humans as they colonized new areas. among well-documented early human introductions are dingoes in australia (brown, ) and polynesian rats [rattus exulans (peale)] on pacific islands (roberts et al., ) . as early europeans explored the planet, other commensal species such as r. rattus, r. norvegicus, and mus musculus expanded their geographic range without deliberate human assistance and are now cosmopolitan in distribution (brown, ) . not all vertebrate pests cohabitat with or are associated with human disturbance of the environment. red deer and feral cats, for example, inhabit much of new zealand's pristine habitats with no human management. most vertebrate translocations fail even with human assistance. failure of exotics to establish may depend on life history parameters, responses to abiotic factors, inability to outcompete native species for resources or enemy free space, or chance (cornell & hawkins, ) . deliberate releases of exotic birds have establishment rates of around to % (veltman et al., ) . establishment estimates for intentional vertebrate releases are biased because successes are more often recorded than failures (ehrlich, ; veltman et al., ) . the amount of effort directed toward introduction is an important variable affecting successful colonization by vertebrates, and establishment rates increase with high levels of management and numbers of individuals released (ehrlick, ; griffith et al., ; williamson & fitter, b; veltman et al., ) . in contrast, organisms that are casually introduced into new areas have much lower probabilities of establishing and proliferating. this phenomenon is expressed in the tens rule, a statistical characterization of probability outcomes for different levels of invasion success (williamson & fitter, a , b . for a variety of plants and animals, a general rule holds that in species imported (i.e., brought into new areas intentionally or accidentally) appear in the wild, in of those now found in the wild become established, and that in of those established with self-sustaining populations become pests (williamson & fitter, b) . following establishment, proliferation, and rise to pest status, control of exotic vertebrates is often prompted by economic, environmental, or conservation concerns. several control strategies may be pursued, the most common being chemical control (e.g., poisoning) and cultural control (e.g., trapping, fencing, and shooting). the least used option has been biological control. chemical and cultural control of vertebrate pests has been covered by hone ( ) and williams and moore ( ) . biological control is the intentional use of populations of upper trophic level organisms (e.g., predators, parasites, and pathogens) commonly referred to as natural enemies to suppress populations of pests to lower densities than would occur in the absence of natural enemies (debach, ; van driesche & bellows, ) . biological control programs for vertebrates have employed all three classes of natural enemies: predators, parasites, and pathogens. in contrast to weeds and pestiferous arthropods, however, biological control as a population suppression tactic for management of vertebrate pests has historically received much less attention. predators of vertebrates in the few instances they have been used have not been particularly successful. some vertebrate predator introductions also had severe impacts on nontarget organisms. consequently, early unpromising results discouraged intensive development of this technology (howard, ; davis et al., ; wood, ) . there is a need for increased effort using biological control agents against vertebrates, especially where resistance to toxins has developed, or behavior and terrain makes chemical and cultural control difficult and expensive (wood, ; bloomer & bester, ) . biological control should be fostered internationally because many countries experience similar problems (e.g., rabbits are agricultural pests in argentina, australia, chile, europe, and new zealand; rats, cats, and dogs attack endangered faunas on many oceanic islands; feral pigs and goats in new zealand, australia, and the united states degrade habitat and threaten endangered flora). biological control can be aided by the establishment of institutions to help coordinate regional and international research activities. for example, in , the australian federal government supported the creation of the cooperative research center for biological control of vertebrate pest populations (also known as the vertebrate biocontrol center), an unincorporated collaborative venture between state and federal organizations with international cooperators (anonymous, a) . the principle research goal of this institution is population suppression of noxious vertebrate species by regulating reproductive rates (tyndale-biscoe, a). a fundamental issue that has important implications for biological control is understanding the regulatory effects predators have on prey populations. determining impact of introduced predators on pest and nontarget populations is becoming increasingly more important as public awareness of potential nontarget impacts increases and the impact of past introductions on nontarget organisms has become clearer (howarth, ; van driesche & hoddle, ) . introductions of vertebrate predators as biological control agents against vertebrates have in some instances had disastrous impacts on nontarget wildlife, especially insular communities that have lacked an evolutionary history with generalist predators (case, ) . an example is the impact the small indian mongoose on native rail populations in hawaii following its release in the s for rat control (loope et al., ) . the mongoose has little demonstrable effect on rats (cagne, ) and mongoose populations are now poisoned to protect native birds (loope et al., ) . exotic predators may enhance the success of introduced pest species by moderating the competitive impact of natives on introduced pests should predators reduce densities of native species (case, ) . on the other hand, there is very good evidence that under certain circumstances introduced exotic predators can regulate target vertebrate pests. in such cases, predator efficacy may be affected by ecosystem complexity; by influence of such extrinsic factors as weather, disease, or human intervention on pest population growth; and by the availability of alternative food sources to sustain predators when pest populations are low. in simple ecosystems such as islands, establishment of reproducing predator populations can result in the extinction of target pests. in the absence of alternative prey, releases of cats for rabbit control on berlinger island near portugal by a lighthouse keeper resulted in the eradication of the rabbits, and subsequently cats died from starvation (elton, ) . in complex communities, alternate prey may be taken when primary prey populations are low for prolonged periods, as is the case for some microtine rodent species in europe. european rodent populations exhibit fluctuations in size as a response to variation in food availability. these fluctuations are also influenced by predation. population cycles are not observed in southern hemisphere countries where european pests and predators have been transferred (korpim~iki & krebs, ; sinclair, ) . rabbit populations in australia and new zealand are maintained at low levels by introduced predators, but regulation only occurs after pest numbers have been reduced by other means. poisoning programs in new zealand in the s and s substantially reduced rabbit densities and populations were maintained at low levels by introduced predators, in particular, ferrets and cats (newsome, ) . similarly in australia, european foxes and cats maintain rabbit populations at low densities following population crashes caused by prolonged hot summers that reduce forage and browse (newsome et al., ; newsome, ) . mouse populations are regulated in a similar fashion by predators (raptors and foxes) in australia (sinclair et al., ) . introduction of two foxes dusicyon culpaeus (molina) and d. griseus (gray) native to mainland chile onto the chilean side of tierra del fuego island regulated rabbit populations after rabbit densities were substantially reduced by the myxoma virus (jaksic & yhfiez, ) . the suppressive action of predators on rabbits in australia has been demonstrated through predator removal experiments [referred to as perturbation experiments by sinclair, ( ) ] in which european foxes and cats were shot from four-wheel drive vehicles at night. removal of predators resulted in rapid rabbit population growth compared with rabbit densities in control plots in which predators were not removed (newsome et al., ) . the "predator pit" first conceptualized by may ( ) describes rabbit regulation in australia and new zealand by generalist predators. the model suggests that once prey populations fall below certain densities (i.e., because of culling or disease) predators can prevent recovery to higher levels. generalist predators achieve this by maintaining relatively high numbers by attacking alternate prey species, and low but persistent levels of predation on species in the pit prevents pest populations from outbreaking. for the rabbit-fox system in australia, a predator pit operates at densities of to rabbits per kilometer of linear transect. below these densities foxes utilize alternate food sources (e.g., native animals) and above this critical density rabbit populations escape regulation by predators (newsome, ) . in new zealand, rabbits are contained in the pit by cats and ferrets when densities are . rabbits per hectare (barlow & wratten, ) . the effect of predators on long-term population dynamics of alternate prey species is generally difficult to disentangle from confounding effects of habitat degradation and competition for food and breeding sites from other introduced species (pech et al., ) . foxes regulate mice and rabbits through positive density dependence at low prey densities. increasing pest densities during outbreaks results in inverse density-dependent predation and type iii functional responses (sinclair et al., ; pech et al., ) . rabbit and mouse populations escape predator regulation when favorable weather provides good breeding conditions, or when predators are controlled by shooting or poisoning (newsome, ; sinclair et al., ; pech et al., ) . predator control may be necessary for lifestock protection or for conservation of endangered wildlife and when implemented resurgence of pest populations occurs (newsome et al., ; newsome, ) . predator numbers may increase when primary prey (e.g., rabbits) are abundant. predation by abundant predators on secondary prey (e.g., native animals) result, leading to declines in secondary prey density. under such circumstances native prey species may only persist in refugia or in areas with artificially reduced predator pressure (pech et al., ) . altematively, declining densities of a primary pest prey species (either through management or disease) can intensify predator attacks on nontarget organisms. therefore, when conservation of endangered natives is a concern, culling of predators may be undertaken either concurrently with the decline in prey density or in anticipation of such a decline (grant norbury, personal communication, ) . in such situations an integrated approach to managing vertebrate pests and their predators is necessary (newsome, ) . predator efficacy can be enhanced either through habitat modification or resource provisioning. cats can maintain rat and mouse populations around farm buildings below environmental carrying capacity as long as they are provisioned with additional food (e.g., milk). dietary supplementation prevents rodent extermination and the subsequent extinction of cats. sustaining a cat population prevents uncontrolled invasions by rodents and low pest densities are maintained (elton, ) . provision of nesting boxes for barn owls (tyto alba javanica) reduces crop damage by rats in malaysian oil palm plantations; rodenticide use declined, and in some instances use was eliminated (wahid et al., ) . changes in management practices can improve predator efficacy. rodent control by tyto alba (scopoli) in pinus radiata don plantations in chile was enhanced by clearing -m wide strips between trees (for owls to maneuver in while in flight) and construction of perches in forests (for resting and surveillance). bam owl numbers and predation rates on rodents increased following habitat modification (mufioz & murfa, ) . under increased predation pressure, rodents will modify foraging behaviors by reducing activity when owls are flying or making hunger calls (abramsky et al., ) . learning in this manner produces behavioral adaptations because of strong selection pressures to minimize predation risks on pest populations (davis et al., ) . parasites or macroparasites (e.g., helminths, lice, ticks, fleas, and other metazoans) do not typically kill their hosts as a prerequisite for successful development as insect parasitoids do. they tend to be enzootic (i.e., remain at fairly constant levels through time) and usually must pass through a free-living stage to complete an entire life cycle (anderson, ; mccallum, ) . the potential of parasites to regulate vertebrate host populations was first proposed as early as (lack, ) and later was demonstrated theoretically with lotka-voltera models in which parasites increased host mortality rates may, ) . parasites act in a positive density-dependent manner by adversely affecting host survival or reproduction dobson & hudson, ; scott & dobson, ) . host parasite load also affects the ability of individual parasites to grow, reproduce, and survive in definitive hosts; and the severity of density dependence on host and parasite fitness is affected by patterns of parasite distribution in host populations (scott & lewis, ) . helminths, for example, tend to be aggregated within host populations so that few hosts are heavily burdened while most are lightly infected (scott & lewis, ) . density-dependent constraints on parasite survival and reproduction occur in the few heavily infected hosts, and under such conditions, helminth population stability is enhanced . furthermore, parasites with low-to-moderate pathogenicity exert stronger regulatory actions on populations than highly pathogenic species that cause their own extinction by killing hosts before transmission (anderson, ) . parasite regulation of vertebrate populations has been observed under field conditions. botfly (cuterebra grisea coquillett) parasitism of voles [microtus townsendii (bachman)] in vancouver canada, is inversely density dependent; and botfly infestation significantly reduces vole survival, reproduction, and development (boonstra et al., ) . the parasitic helminth trichostrongylus tenuis (cobbold) is the primary agent responsible for long-term population cycles in red grouse [lagopus lagopus scoticus (latham)] inhabiting scottish heathlands (dobson & hudson, ) . the regulatory effect of t. tenuis has been demonstrated by reducing parasite infestations with helminthicides in experimental birds. treated grouse showed increased overwintering survival, clutch sizes, and hatching rates when compared with untreated birds (dobson & hudson, ) . in the laboratory, introduction of the nematode heligmosomoides polygyrus dujardin reduced mice densities by % in comparison with control populations. reduction of nematode transmission rates and elimination of parasites with helminthicides allowed infested mouse populations to increase (scott, ) . although host and parasite densities in this study were higher than those found in nature, the data showed that introduction of a parasite regulated host population abundance. the potential effectiveness of nematodes as biological control agents in field situations has been evaluated for control of the house mouse, an introduced pest in australia (singleton & mc-callum, ; spratt, ) . mouse (mus domesticus) populations erupt every to years in cereal-growing regions of southeastern australia (singleton & mccallum, ; mccallum, ) and economic losses to mouse plagues exceed $ million (australian) (beckman, ; singleton, ) . outbreaks are associated with high autumn rainfalls following prolonged periods of drought that extend the growing season for grasses that set seeds. this high-quality food source increases high mouse survivorship and breeding throughout winter. population crashes occur when food supplies are exhausted (singleton, ) . saunders and giles ( ) suggested that droughts are necessary to remove the regulating effects of natural enemies, and this removal combined with favorable weather conditions permitted mouse numbers to increase rapidly. capillaria hepatica (bancroft), a parasitic nematode that infests mice, is naturally occurring and widely distributed in pestiferous rodents in coastal areas of australia. it is, however, absent in mouse populations in cereal-growing areas . this nematode is unique because it is the only known helminth with a direct life cycle that requires host death for transmission. female nematodes deposit eggs in the host's liver; and these eggs are liberated by predation, cannibalism, or necrophagy with subsequent digestion of infected liver. unembryonated nematode eggs voided after ingestion undergo embryonation to become infective and are probably consumed when mice preen their fur and feet (fig. ) . ground beetles (carabidae) may vector c. hepatica eggs after they have been eaten (mobedi & arfaa, ). firststage larvae emerge from ingested embryonated eggs and move into the liver through the hepatic portal system (wright, ) . nematode infestation significantly reduces natality and numbers of young mice weaned by infected females (mccallum & singleton, ; singleton & mc-callum, ; . capillaria hepatica is associated with introduced rat and mouse species in urban areas, and naturally occurring infections in native australian mammals are rare probably because of the susceptibility of nematode eggs to ultraviolet radiation and desiccation singleton et al., ) . native australian mice and marsupials are susceptible to experimental infection in laboratories . rats (r. norvegicus and r. rattus) are major reservoirs for c. hepatica in urban areas and infestation rates range from to % (childs et al., ; singleton et al., ) . infestation levels are lower in sympatric mice populations ( to %, singleton et al., ) . low rat numbers in cereal-growing regions of australia may be a factor contributing to the nonpersistence of c. hepatica in these areas . infestation of nonrodent mammals by c. hepatica is rare but has occurred in rabbits (gevrey & chirol, ) , dogs (leblanc & fagin, ) , horses (munroe, ) , and humans (pannenbecker et al., ) . human infections can be treated successfully (pereira & franca, ) . exploratory models investigating the impact of c. hepatica on mouse populations indicated that the requirement of host death for parasite transmission is strongly destabilizing. in the absence of resource limitation mouse densities increase similarly to disease-free populations before parasites have an impact and infected populations decline in density (mccallum & singleton, ) . slow regulation of mouse populations occurs because of the need for host death for transmission. consequently, the nematode's life cycle operates on the same time scale as that of its host instead of being orders of magnitude faster, as is the case with other parasites that do not require host death for transmission (mccallum & singleton, ; singleton & mc-callum, ) . the destabilizing influence of c. hepatica on mouse parasitology today, , [ ] [ ] [ ] [ ] populations may contribute to localized host and parasite extinctions. these extinctions, coupled with very low mouse densities in nonoutbreak years, result in population bottlenecks and may explain why nematodes do not persist in regions where mouse outbreaks occur. soil type, temperature, and moisture content do not affect nematode egg survival and embryonation under favorable conditions in outbreak regions (spratt & singleton, ) . outbreak intensity can theoretically be reduced by c. hepatica if populations are inoculated early, preferably year before an outbreak is expected (mccallum, ) . releases of high doses of nematode eggs in the summer or autumn when mouse densities are sufficient to enable high levels of transmission may offer the best chance for successful control (mccallum & singleton, ; mccallum, ) . field experiments in enclosures and with increasing populations of free-ranging mice have failed to demonstrate long-term regulation on mouse population growth with periodic inoculative releases of c. hepatica eggs. unexpected declines in control populations (i.e., populations not treated with nematodes) have to some degree masked the effect of c. hepatica on mice populations singleton et al., ; singleton & chambers, ) . transmission of c. hepatica in treated populations is not density dependent and can occur at low levels for to months. transmission rates show seasonal trends influenced by soil temperatures and increasing aridity singleton & chambers, ) . improved understanding of the influence of factors (such as temperature and rainfall on nematode persistence, survival, and transmission in field situations) and timing of releases of parasite eggs may improve releases of c. hepatica for control of mouse outbreaks (singleton et al., ; singleton & chambers, ) . vertebrate species that successfully colonize new habitats have reduced parasite loads in comparison with mother populations from which they originated (dobson & may, ) . lower infestation levels probably occur because individuals that make up small founding populations either were uninfected or had only a limited subset of the total potential parasite species found in the area of origin, or intermediate hosts required for parasite persistence were absent in the new range. sparrows and starlings, both successful colonizing species from europe, have two to three times fewer parasites in north america compared with populations from which they originated. populations established outside of europe may have benefited from reduced parasite burdens, although there are no quantitative data to indicate that this aided establishment and proliferation (dobson & may, ) . investigating the role of parasites on population dynamics of rabbits in europe with the view for possible introduction into countries where rabbits are pests is also warranted (boag, ) . introduced mammals such as rats, goats, and cats on oceanic islands exhibit depauperate parasite faunas (dobson, ) . fewer parasites coupled with presumed low genetic diversity of small founding populations, and reduced selection pressures for parasite resistance may make these pest vertebrates vulnerable to introduced host-specific parasites. the ideal parasite introduced into a high-density pest population that originated from a small founding population should have low-to-intermediate pathogenicity, because such parasites establish and maintain themselves in populations at lower densities than more pathogenic species do . macroparasites that reduce both host longevity and fecundity may have the potential to cause sustained reductions of host population densities (dobson, ) . low genetic variability among target populations should theoretically enable introduced parasites to become more evenly distributed among hosts, and reduction in parasite aggregation would increase natural-enemy efficacy (dobson & hudson, ) . the possibility of reassociating parasites with vertebrate pests is not limited to mammals and birds. host-specific parasites may have the potential to reduce reproduction and longevity of pest reptile (dobson, ) and amphibian species (freeland, ) . the brown tree snake is the proximate cause of native bird extinctions on guam following its accidental introduction after world war ii on military equipment (pimm, ; savidge, ; jaffe, ; rodda et al., ) . the snake also has caused declines of native reptile and small mammal populations, and enters houses and attacks sleeping human infants (rodda et al., ) . additionally, the brown tree snake has caused eco-nomic losses by adversely affecting domestic animals (e.g., chickens and pets), and high densities of snakes on power lines regularly cause short circuits that interrupt electrical supplies and necessitate repairs. control of the brown tree snake has been attempted through trapping, but the snake's extreme preference for live bait over artificial lures has made this approach impractical (rodda et al., ) . the brown tree snake mnative to eastern indonesia, the solomon islands, new guinea, and northeastern australiambelongs to the family colubridae. it is the only member of this family on guam. there is one native species of snake on guam, the blind snake, rhamphotyphlopys braminus (daudin), which belongs to the family typhlopidae and is the only snake occurring on many islands in the central pacific region (t. fritts, personal communication, ) . the brown tree snake has extended its range and is now established on the previously snake-free island of saipan, and this snake has been intercepted in hawaii; corpus christi, texas, and spain (rodda et al., ) . given the propensity for the brown tree snake to be dispersed to new habitats within cargo loads on planes and ships, the major social, economic, and ecological problems that are caused on islands after colonization, in addition to its distant taxonomic relationship to snakes common to pacific islands, make the brown tree snake an excellent target for biological control. the taxonomic relationship between colubrids and typhlopids may simplify the task and reduce the cost of finding natural enemies unique to the brown tree snake. parasites or pathogens that are host specific just to the family (i.e., colubridae) or genus (i.e., boiga) level may be safe to nontarget snakes (e.g., typhlopids) because these organisms have not evolved the ability to cause disease in distantly related hosts. extreme caution should be exercised when implementing a biological control program against vertebrate pests with parasites. parasites and pathogens can pose major threats to populations of endangered animals (mccallum, ; mccallum & dobson, ) . the susceptibility of nontarget organisms, especially endemic species, to infection by candidate biological control agents should be investigated thoroughly prior to parasite releases. reassociating parasites that preferentially infect a competitively dominant pest species may increase species diversity of invaded communities by reducing the pest's prevalence. in this instance, the natural enemy would assume the position of a keystone parasite (marcogliese & cone, ) . pathogens or microparasites include viruses, bacteria, and protozoans. pathogens tend to be unicellular and exhibit epizootic (i.e., boom or bust) life cycles due to rapid proliferation in hosts (anderson, ; mccallum, ) . the potential of pathogens to regulate vertebrate population densities by reducing the longevity and fecundity of infected hosts has been demonstrated theoretically with mathematical models and by perturbation experiments using vaccines (smith, ) . as with macroparasites, models indicate that microparasites of intermediate pathogenicity are more effective biological control agents (anderson, ) . highly virulent pathogens kill themselves by destroying hosts before they can be transmitted and avirulent strains are not transmitted because they are removed by the immune system. the immune system is theorized as being responsible for maintaining the intermediate virulence of vertebrate microparasites (anita et al., ) . pathogens that are readily transmitted (i.e., microparasites spread by water, air, and vectors) or have high-density host populations are more contagious than those with low transmission rates (i.e., spread is by host-to-host contact) or low host densities (ebert & herre, ) . new associations between pathogens and novel hosts are generally not more harmful than those that have evolved closely with the host. experimental evidence indicates that novel disease-causing organisms are on average less harmful, less infectious, and less fit than the same parasite strain infecting the host it is adapted to (ebert & herre, ) . also, a microparasite's ability to infect and exploit novel hosts decreases with increasing geographic and presumably genetic distance from the host to which the pathogen is adapted (ebert, ) . exceptions do occur, however, and pathogens can have devastating impacts on hosts that have no evolutionary history with the disease organism. an example is the myxoma virus, the causative agent of myxomatosis in european rabbits. the use of this natural enemy against rabbits in australia and europe has been the most thorough biological control program against a vertebrate pest. the myxoma virus is a member of the genus leporipoxvirus (poxviridae) and originated from south america where it was first recognized as an emerging disease of european rabbits in laboratories in montevideo, uruguay, in . infected laboratory rabbits died of a fatal febrile disease that caused tumors on the head and ears. the tumors resembled myxomas (a benign tumor composed of connective tissue and mucous elements) and the disease was subsequently named infectious myxomatosis of rabbits (fenner & marshall, ; fenner & ratcliffe, ; fenner, ) . the indigenous host for myxoma virus in south america is the forest rabbit [sylvilagus brasiliensis (linnaeus)]. unlike its effect on european rabbits, myxoma inoculum injected into forest rabbits caused benign fibromas at the site of inoculation that persisted for many months, although death did not occur. mosquitoes were implicated in vectoring the disease from forest rabbits to european rabbits being bred in south american rabbitries. another leporipox-virus has been isolated in california from the brush rabbit, sylvilagus bachmani (waterhouse), and is closely related to the myxoma virus (fenner & marshall, ; fenner & ratcliffe, ; fenner, ; fenner & ross, ; ross & tittensor, ) . myxoma virus has been used in australia, europe, chile, and argentina for biological control of european rabbits. the virus was first imported into australia from brazil in and but was not released (fenner & ratcliffe, ) . work by australians with the virus began again in the united kingdom in and continued with caged rabbits on wardang island off the south coast of australia. the virus was successfully established on mainland australia in (fenner, ) and within years it had established itself over most of the rabbit's range (fen-ner& ratcliffe, ) . the virus initially had a major impact on the estimated million rabbits and on the damage they caused, reducing population density by to %. efficacy was dependent on climate and rabbit population susceptibility. populations have subsequently increased and stabilized at around million because of myxomatosis. damage attributable to rabbits still amounts to $ million (australian) annually, including both lost agricultural production and cost of control applications (robinson et al., ) . in addition to agricultural losses, rabbits severely affect native flora by eating foliage and inducing wind and water erosion of soils by overgrazing. native fauna are also affected as rabbits out-compete indigenous herbivores and dense rabbit populations sustain exotic predator populations that feed on native animals (gibb & williams, ; myers et al., ; robinson et al., ) . within a few years of the initial panzootic, field isolates of the virus showed less virulence when compared with the original strain that had been released. the original strain killed > % of laboratory rabbits on average . days after infection, while circulating strains caused % mortality after . days. genetic resistance in rabbits was also detected (fenner & marshall, ; fenner & ratcliffe, ) . dual natural selection had occurred, the virus had attenuated, and rabbits had increased in resistance to the disease. mosquitoes have been responsible for vectoring myxoma virus in australia. the european rabbit flea, spilopsylus cuniculi (dale), an important vector in europe, was introduced into australia in and increased the geographic distribution of the disease. this flea did not persist in areas with rainfall < mm. the xeric adapted spanish rabbit flea, xenopsylla cunicularis smit, was introduced in and active redistribution is still ongoing (fenner & ross, ) . new zealand also has inordinate numbers of rabbits, and attempts to establish the myxoma virus from to failed because of inclement weather and a paucity of suit-able arthropod vectors. further attempts at establishment were not undertaken because poisoning programs had reduced rabbits to very low numbers, additional control expenditure was unjustifiable, and the new zealand public was not in favor of using lethal myxoma virus for rabbit control on humanitarian grounds (gibb & williams, ) . until the s, myxomatosis was the only disease known to severely affect rabbit numbers. a second highly contagious viral disease emerged in the mid- s and was accidentally introduced onto mainland australia (o'brien, ) . it is the first pathogenic natural enemy to have established in new zealand for biological control of rabbits. rabbit calicivirus disease (rcd) [also known as rabbit hemorrhagic disease virus (rhdv)] emerged as a fatal disease in in angora rabbits exported from east germany to jiangsu province of china (liu et al., ) . in , the disease appeared in italy where million rabbits were estimated to have died. the disease spread rapidly through rabbit populations in europe reaching the united kingdom in (chasey, ) . the probable mechanism for dispersal in continental europe was the movement of live rabbits and rabbit products. transmission of rcd from france into coastal areas of southeast england is thought to have occurred by wind-borne aerosols containing virus, birds, and transchannel ferry traffic (chasey, ) . outbreaks of rcd occurred in mexico in and (gregg et al., ) and in rrunion island in the indian ocean in . movement of rcd to these areas probably occurred with imports of frozen rabbit carcasses from china because the virus can survive freezing to temperatures of - ~ (chasey, ) . the rcd virus belongs to the caliciviridae and consists of a positive sense, single-stranded rna genome, enclosed by a sculptured capsid composed of multiple copies of a single major protein of kda, and is to nm in diameter (ohlinger et al., ; parra & prieto, ) . disease symptoms are characterized by high morbidity and mortality in rabbits over weeks of age. younger rabbits often survive infection and may develop antibodies to rcd virus (nagesha et al., ) . clinically, rcd symptoms are expressed after an incubation period of to h in which a febrile response and increasing lethargy are observed. infected rabbits typically die within to h postinfection and % mortality is observed after days. necropsies show a pale swollen friable liver, enlarged spleen, and clots in blood vessels. death is ascribed to acute necrotizing hepatitis and possible hemorrhaging (fuchs & weissenbrck, ; studdert, ) . however, necropsies close to the time of death show an absence of hemorrhaging and inclusion of hemorrhagic in the name of this rabbit disease that indicates the cause of death is misleading (studdert, ) . a different viral disease is responsible for european brown hare syndrome (ebhs) which causes severe hepatic necrosis in hares (lepus europaeus pallas and l. timidus linnaeus). the disease was first recorded in sweden in , and spread through continental europe and reached the united kingdom in (fuller et al., ) . in sweden, losses of hares to ebhs occurred years prior to sympatric rabbit populations developing rcd. similar observations were made in the united kingdom where hares began dying from ebhs years before rcd was observed in rabbit populations (fuller et al., ) . electron microscopy, nucleotide sequencing, and experimental cross-transmission studies have indicated that rcd virus and ebhs virus are closely related (le gall et al., ) but distinct members of the caliciviridae (chasey et al., ; nowotny et al., ) . disease symptoms are generally similar for rabbits and hares but show distinguishing characteristics in necrosis of liver lobules and clotting of blood vessels (fuchs & weissenbrck, ) . serological studies on rabbit sera collected in from czechoslovakia and austria indicate that rcd virus probably evolved from an apathogenic strain endemic to europe from at least this time (nowotny et al., ) . studdert ( ) speculates that the causative agent of rcd probably existed in europe as a quasi species, a collection of indifferent mutants with a variety of accumulated nucleotide changes. in this scenario, mutants occupied a specific ecological niche until one strain better adapted to prevailing conditions became the dominant member of the population. adaptation may have occurred because mutations caused increased virulence in an avirulent rabbit virus or increased the host range of hare-infecting viruses by allowing mutant strains to bind more efficiently to surface receptors on rabbit hepatocytes. given studdert's ( ) speculative scenario, rcd virus may be a highly evolvable organism. european rabbits appear to be the only animals susceptible to infection by rcd virus, and vaccines have been developed to protect domestic animals (boga et al., ) . other rabbits including cottontail rabbits (sylvilagus spp.), black-tailed jack rabbits (lepus californicus gray), volcano rabbits [romerolagus diazi (ferrari-prrez)] (gregg et al., ) , and hares (gould et al., ) are not affected. the limited host range of rcd virus makes it an obvious candidate for use in a biological control program against european rabbits in new zealand and australia. a joint biological control program between these two countries using rcd virus was initiated in and a strain of virus from the czechoslovakia republic was imported into australian quarantine facilities in to test effects on nontarget species (robinson & westbury, ) . host-specificity testing of nontarget species in australia for susceptibility to rcd virus further verified the limited host range of this natural enemy. test subjects in-cluded domestic lifestock (horses, cattle, sheep, deer, goats, pigs, cats, dogs, and fowls) , noxious exotic vertebrates (foxes, hares, ferrets, rats, and mice), native mammals (eight species), birds (five species), and reptiles (one species). there was no evidence for viral replication, clinical signs, or lessions in any organisms tested (gould et al., ) . artificial inoculation of rcd virus in north island brown kiwis (apteryx australis mantelli bartlett) and lesser short-tailed bats (mystacina tuberculata gray), both native to new zealand, also failed to produce disease symptoms (buddle et al. ) . the apparent host specificity of rcd virus to rabbits, rapidity of action, and the capacity to infect rabbits from other rabbits, [through feed and feces, or from a contaminated environment (o'brien, ) ] prompted further evaluation of this biological control agent under field quarantine conditions in australia. studies monitoring the effects of rcd virus on rabbit populations were initiated on wardang island near adelaide off the south coast of australia in (rudzki, ; robinson & westbury, ) . in september , rcd breached quarantine and appeared on mainland australia, possibly carried there by calliphorid flies and onshore winds (cooke, ; lawson, ) . attempts at containment failed (seife, ) . within months of the initial discovery of rcd virus on the mainland, an estimated million rabbits were killed in south australia. in dry areas, to % of infected populations died (anderson, ) with dead rabbits averaging per hectare. elsewhere, fatality rates were closer to % (anonymous, b) . in the period from october to november , an estimated total of million rabbits died from rcd in south australia and the majority of surviving rabbits were less than weeks of age (cooke, ) . the development of resistance in young rabbits may have profound effects on the long-term population dynamics on the rabbit-rcd virus system. ten arthropod vectors of rcd virus have been identified and include flies, mosquitoes, and rabbit fleas (anonymous, b) . rates of spread of rcd are greatest in spring and autumn at to km a day and are correlated with peaks of insect activity. dispersal of the disease probably has been assisted by humans moving contaminated material to new areas (cooke, ) . increased attacks on native fauna by exotic predators such as foxes because of declines in rabbit numbers do not appear to have occurred because predator populations have declined with rabbit numbers (anonymous, b). the virus is now endemic in australia and will probably be officially declared as a biological control agent under the biological control acts of the commonwealth and states (robinson & westbury, ) . rcd virus was smuggled into the south island of new zealand by high country farmers in august and illegally disseminated by feeding rabbits carrots and oats satu-rated with contaminated liquefied rabbit livers. a network of cooperators spread the virus over large areas of the south island and its subsequent spread (human assisted through the movement of carcasses, baiting, and insect vectors) made containment and eradication of the disease impossible. such actions by farmers clearly violated new zealand's biosecurity act, which was enacted in part to protect agriculture from unwanted introductions of pests. the new zealand government has sanctioned controlled virus releases into new areas. the short-term impact of rcd on new zealand rabbit populations has resulted in to % mortality in central otago and large-scale field studies are planned (g. norbury, personal communication, ) . cats on oceanic islands have been subjected to biological control with pathogens. six cats were introduced onto marion island in the indian ocean in (howell, ) ; by , numbers were in excess of and were increasing an average of % per year (van rensburg et al., ) . populations were sustained by consuming approximately , seabirds yearly and cats were probably responsible for the local extinction of the common diving petrel pelecanoides urinatrix (gmelin) (bloomer & bester, ) . surveys of cats on marion island revealed the presence of feline herpes virus and feline corona virus, but the highly contagious feline parvo virus was absent in the population (howell, ) . initiation of a biological control program with feline parvo virus, the causative agent of feline panleucopenia, began in with the release of artificially inoculated feral cats collected from the island (howell, ) . the disease reduced cat numbers by % after years by reducing fecundity and increasing mortality of juvenile cats (van rensburg et al., ) . virions found in high concentrations in feces, urine, saliva, and vomit were transmitted through direct contact between cats or contact with contaminated objects (howell, ) . annual declines of cat numbers were % from to . this rate decreased to % per year from to and was accompanied by lower titers of virus in serum samples collected from feral cats, indicating that viral efficacy was decreasing (van rensburg et al., ) . at reduced densities, hunting and trapping became viable and have been incorporated into an ongoing eradication program that may be assisted by the use of trained dogs (bloomer & bester, ) . sexually transmitted diseases have adverse effects on domestic and wild vertebrates by reducing survival, conception rates, and numbers of offspring born and successfully weaned (smith & dobson, ) . rabbits are susceptible to infections of venereal spirochetosis (treponema cuniculi), which causes sterility (smith & dobson, ) . goats can develop trichomoniasis, a sexually transmitted disease caused by the flagellated protozoan trichomonas foetus (reidmuller). this pathogen has been suggested as a bio-logical control agent for goat populations on oceanic islands that lack this microparasite (dobson, ) . sexual transmission of diseases may further guarantee host specificity in biological control programs. it also enhances the ability of parasites and pathogens to persist in low-density populations or solitary species (e.g., predators). the rate of spread of sexually transmitted organisms is tightly correlated with mean and variance of the numbers of sexual partners per host because of the need for host-tohost contact (horizontal transmission) for transmission. host population density is not important with respect to persistence or rate of spread of sexually transmitted diseases. this property, coupled with asymptomatic carrier states, long infectious periods, or vertical transmission (infective propagules are passed from mother to offspring), greatly enhances the ability of pathogens to persist in lowdensity host populations (smith & dobson, ) . because sexually transmitted organisms can persist in low-density populations or populations of declining density, the potential of genetically engineering sexually transmitted viruses to sterilize infected hosts is being investigated (barlow, ) . viruses that have antigens from the host sperm, or the zona pellucida around host eggs engineered into the genome provoke an immune system response that renders the recipient sterile. immunocontraception (also referred to as immunosterilization) as a means to control noxious vertebrates is being actively pursued by australia and new zealand (mccallum, ) . an alternative approach to immunocontraception is to use genetically modified microparasites to prevent lactation in females so that juveniles are not successfully weaned or to interfere with hormonal control of reproduction (cowan, ; jolly, ; rodger, ) . many species that become pests are distinguished from nonpestiferous species by their higher intrinsic rates of increase (rm). pest vertebrates have high rm values characterized by large litters, and by maturing sexually at young ages. agents that reduce reproductive rates may be more effective for control than mortality-inducing biological control agents are because resistance development should take longer to occur and population recovery would be slower (tyndale-biscoe, b) . resistance development may be further delayed by combined use of multiple agents that affect fertility in different ways [e.g., using agents that cause sterilization, alter levels of reproductive hormones, or affect lactation (cowan & tyndale-biscoe, ) ]. in sexually reproducing vertebrates, proteins associated with male and female gametes are potentially foreign antigens in the opposite sex. exposure to reproductive antigens occurs when females receive sperm and accessory fluids from males during copulation. as a general rule, females do not develop antibodies to these antigens because physiological and immunological mechanisms have evolved to prevent this (robinson & holland, ) . inoculation of sperm into females of the same species either subcutaneously or intramuscularly produces high sperm antigen antibody titers in recipients. in most cases, this causes either permanent or temporary infertility in females. such results indicate that sperm antigens in the reproductive tract are tolerated and that exposure to these antigens by different routes overcomes protective mechanisms, with infertility resulting (robinson & holland, ) . sperm antibodies in females that can arise from either systemic or local immune responses are found in cervical mucus, genital fluids (e.g., endometrial, tubal, and follicular fluids), and blood. antibodies bind to sperm, often in specific locations such as the head, midpiece, tail shaft, or tail tip. once bound to sperm, antibodies cause agglutination (e.g., irreversible binding to cervical mucus that normally aids sperm transport) or immobilization of sperm. antibodies may also interfere with acrosome reactions preventing ovum penetration and fertilization, or they block the binding of sperm to the zona pellucida (shulman, ) . the zona pellucida (zona) that surrounds growing oocytes and ovulated eggs is antigenic and available to circulating antibodies during oocyte growth and ovulation. nonreproductive tract inoculation of females with zona preparations leads to infertility (millar et al., ) . antibodies produced in response to administered zona antigens bind to the zona and prevent sperm penetration (millar et al., ) . zona glycoproteins are highly conserved among mammals, for example, nonspecific pig zona preparations cause infertility in humans, primates, dogs, rabbits, horses, and deer (robinson & holland, ) . a major objective in immunocontraception research is isolation of species-specific zona glycoproteins that do not cause sterility induced by immune response in species from which zona preparations were not derived. low variability among zona glycoproteins may limit the number of species-specific zona preparations for immunocontraception (millar et al., ) . immunocontraception for wildlife population control has been successfully implemented for horses (equus caballus linnaeus) (kirkpatrick et al., (kirkpatrick et al., , . free-ranging feral mares inoculated by dart gun with porcine zona pellucida showed depressed urinary estrogen concentrations and failure to ovulate. zona booster inoculations given years after initial inoculations prevented conception in treated horses for a third year compared with control populations that were not vaccinated. contraceptive effects were reversible after years of consecutive treatment, but prolonged treatment ( to years) with zona preparations caused irreversible ovarian dysfunction and fertility loss (kirkpatrick et al., (kirkpatrick et al., , . similar results have been achieved with porcine zona pellucida inoculations in whitetail deer [odocoileus virginianus (zimmerman)] (kirkpatrick et al., ) . gametic antigens that induce immune response can be administered by baits that are ingested by target organisms or can be inoculated directly into hosts with darts or bullets (tyndale-biscoe, b). injection of foxes with sperm antigens reduces fertility from to %. baits are considered the favorable method for delivering antigens to foxes in australia. potential baits include dried meats that contain microencapsulated antigens. use of recombinant bacterial vectors (e.g., salmonella typhimurium) also are being considered. an orally administered agent needs to reach the lower gastrointestinal tract to stimulate a response in the common mucosal immune system in the gut-associated lymphoid tissue. this in turn induces mucosal immunity in the reproductive tract of female foxes and causes sterilization (bradley et al., ) . at present, an effective bait specific to foxes that is environmentally stable and easy to manufacture has not been developed. nontarget impact is a concern because most antigens exhibit some specificity to the family level only. effective vaccines for rabies have been delivered as oral baits to foxes in europe, demonstrating the baiting technique is an effective dissemination method (bradley et al., ) . models indicate density-independent factors such as drought and rain (which affect pasture growth and rabbit numbers) strongly influence the effectiveness of baitdelivered fertility control in reducing fox abundance . an alternative proposal to deliver antigens orally is to develop transgenic plants to produce and deliver gametic antigens in palatable form to herbivorous pests. plants could be sown over target areas and allowed to become self-propagating vaccines. transgenic seeds, fruits, or leaves (e.g., transgenic carrots or maize) could be harvested and used as oral baits delivered to specific sites such as fenced watering points that allow pest animals access while excluding lifestock (smith et al., ) . baiting is an expensive form of control that requires monitoring of dosage and uptake rates and multiple areawide applications. problems of hormonal modification of behavior and delayed population control are additional drawbacks. one advantage is that baits can be used to treat localized populations that are problematic. similar shortcomings exist with antigen inoculations by projectiles where cost estimates are significant. to control the estimated , wild horses in australia with dart-delivered porcine zona pellucida would cost $ (australian) per horse per year compared with cents for permanent control with a bullet (tyndale-biscoe, ) . lethal methods of control provide immediate impact on pest populations and reduce pest status rapidly, with control being quickly observable. in contrast, fertility impairment is not immediate, population responses are delayed, and large proportions of populations need to be sterilized for this technique to be effective. large-scale distribution of gametic antigens might be possible through releases of host-specific microparasites expressing species-specific antigen genes (tyndale-biscoe, a , b . self-spreading and replicating parasitic vectors that have been genetically engineered and that may require periodic reinoculation into populations are analogous to augmentative biological control programs with traditional natural enemies (e.g., parasitoids, predators, or pathogens) released periodically for the control of pest arthropods. host-specific viruses carrying foreign dna could be cheap and effective biological control agents that have the potential to disseminate widely by sexual transmission, contagion, or arthropod vectors. the selected micro-or macroparasite must be able to carry foreign dna coding for gametic antigens, as well as promoters to express foreign genes and cytokines to enhance effectiveness (tyndale-biscoe, b). such agents must be able to reduce growth rates of infected populations and to maintain reproductive rates at lower levels (caughley et al., ) , and should not interfere with sexual behavior or social organization (caughley et al., ; robinson & holland, ; tyndale-bisoce, b) . with some pests such as rabbits and foxes, dominant members of populations make the main contribution to reproduction and inhibit breeding by subordinate members by occupying prime territories. ideally, a sterilizing agent should not change social hierarchies by allowing individuals with lower social status to successfully rear more offspring because this will cause pest populations to increase substantially (caughley et al., ) . genetically engineered agents should sterilize females because models predict greater population suppression with infertile females than with sterilized males (barlow, ; caughley et al., ) . in the absence of arthropod vectors, sexually transmitted diseases engineered to cause sterilization are superior to nonsexually transmitted ones because multiple matings with sterilized females increases contact rates and the competitive ability of the engineered agent with nonsterilizing strains. the impact of immunocontraception is further enhanced if the sterilizing agent causes limited host mortality and there is low naturally occurring immunity to sexually transmitted diseases (barlow, ) . sexually transmitted herpes-type viruses are being proposed as vectoring agents to induce sterilization in brushtail possums in new zealand (barlow, ; barlow, ) . the recently identified borna disease virus that causes wobbly possum disease in new zealand may be a suitable alternative to a herpes virus (atkinson, ) . the myxoma virus and murine cytomegalovirus are being investigated as gamete antigen delivery agents for rabbits and mice, respectively, in australia (mccallum, ; tyndale-bisoce, b; shellam, ) . four potential insertion sites for genes coding for gametic antigens have been identified in myxoma virus and recombinants have been constructed to express two esherichia coli (escherich) enzymes and influenza virus hemagglutinin genes. the ability of a novel myxoma virus to compete and spread among existing myxoma strains in field situations has been demonstrated by monitoring the spread of virus containing identifiable gene deletions (robinson et al., ) . the myxoma virus that can express foreign genes may operate as a vector for gametic proteins (robinson et al., ) . work is continuing on isolating and inserting rabbit gamete antigen genes into the myxoma virus genome (robinson et al., ) . the responses of experimental rabbit and fox populations in australia to imposed sterility by surgical ligation of fallopian tubes in females have been studied in an attempt to simulate the effects of virally mediated immunocontraception after recombinant virus establishment in wild populations. this technique prevents conception among predetermined proportions of females in populations without interfering with hormones or reproductive behavior (williams & twigg, ) . the dynamics of rabbit populations enclosed by rabbit-proof fencing that exhibited , , , or % sterilization of females were studied in each of two locations in western and eastern australia where climate patterns differed. females born into treatment populations were trapped and sterilized to maintain the same overall sterility levels (williams & twigg, ) . juvenile rabbits born into populations with sterilized females exhibited greater survivorship because of lowered competition for resources. this greater survival compensated for decreased fertility, but recruitment rates were ultimately constrained by environmental factors (e.g., depletion of vegetation). in populations with % sterility, reduced juvenile mortality did not compensate fully for lowered reproduction, smaller numbers of rabbits were recruited into these populations, and numbers subsequently declined. these results indicate that levels of sterilization with a genetically altered micorparasite have to reach at least % to achieve reductions in population density (williams & twigg, ) . surgical sterilization does not affect reproductive behavior in treated populations. sterile dominant female rabbits maintain hierarchical dominance, increased body weight over control females, continued to defend prime territory, and engaged in normal reproductive behavior including breeding burrow construction (tyndale-bisoce, b). birth rates of sexually mature females were in direct proportion to the level of fertility in experimental populations, indicating that fertile females did not respond to female infertility or decreased densities of young by producing larger litters (williams & twigg, ) . sterilized females tended to live longer than unsterilized females. this increased longevity suggests that sterile females may proportionately increase as treated populations reach an equilibrium density. obviously, larger proportions of sterile females reduce population productivity and the numbers of fertile females that a sterilizing microparasite would have to infect and sterilize. higher proportions of sterile females may reduce numbers of infective individuals harboring sterilizing microparasites and numbers of vectors (e.g., fleas that would spread an engineered myxoma virus), and may contribute to decline of transmission rates. these interactions need to be clarified and mathematical models may be of use here (williams & twigg, ) . engineered microparasites that sterilize pest animals offer the possibility of humane control without killing or causing animals to suffer the effects of debilitating disease. as a form of biological control, immunocontraception may also reduce the need for broadcast distribution of toxins for pest suppression, thereby reducing environmental contamination and nontarget mortality. this is of special concern when pests inhabit suburbs, urban parks, government and state campuses, nature reserves, military bases, or other areas where lethal controls may no longer be legal or safe (kirkpatrick et al., ; williams, ) . the concept of virally mediated immunocontraception has generated considerable debate on legal and ethical issues concerning releases of engineered microorgansims into the environment. once contagious recombinant agents that cause permanent sterilization in animals are released into the environment they cannot be recalled (tyndale-bisoce, ) . several potential risks are recognized. first, engineered viruses that are host specific and contain species-specific antigens could mutate and infect and sterilize nontarget species after release (anderson, ) . under such conditions it may be difficult if not impossible to contain and eradicate a mutant virus from an infected animal population that is abundant, secretive, and free ranging. second, sterilizing viruses either might cross international boundaries accidentally or be maliciously moved to sterilize desirable organisms in new areas (tyndale-bisoce, b) . for example, viruses engineered with little host specificity to sterilize widely dispersed marsupial pests in new zealand may enter australia and infect endangered wildlife (rodger, ; mccallum, ) ; engineered myxoma viruses may spread from australia into the americas and sterilize native rabbit species (tyndale-biscoe, ) . third, dart-delivered contraceptives used for wildlife control in the past have had adverse effects on individuals within target populations. changes in morphology of repro-ductive organs, secondary sexual characteristics, and behavior have been observed. viruses that induce sterility could alter genetic profiles of target populations because infectious agents may act as a new reproductive disease and individuals may exhibit differential susceptibility (nettles, ) . fourth, public concerns over the use of viruses and genetic engineering indicate substantial apprehension about the use of sterilizing viruses for pest management, these fears that need to be fully alleviated may delay or prevent field trials and widespread application (lovett, ) . despite potential drawbacks, immunocontraception is a potentially cost-effective method for reducing pest impact on endangered native species (sinclair, ) and on agricultural yields, and is an additional tool for sustainable pest management (williams, ) . a sterilizing agent that does not cause painful disease symptoms is an ethically acceptable form of pest control that is justifiable from animal rights perspectives, because it does not cause the suffering typical of current lethal methods (e.g., trapping, shooting, poisoning, and introduced disease) ( oogjes, ; singer, ) . under certain circumstances, the use of vectors to disseminate genetically engineered viruses is warranted (mccallum, ) . experience with the myxoma virus in australia indicates that it has not been deliberately or accidentally spread to any other country since its introduction in the s because of either the lack of suitable arthropod vectors or the inability of the virus to establish where different strains are already present. this history may indicate possible difficulty for unintentional establishment of genetically engineered microparasites in new areas, and establishment of engineered myxoma viruses may be possible only with carefully timed and repeated releases into rabbit populations (tyndale-biscoe, ) . however, such safeguards may be moot if a highly competitive sterilizing strain is engineered and released. quarantine legislation designed to prevent accidental or intentional but illegal importation of unwanted organisms would be exercised by countries under current international obligations and should impede establishment in new countries if rigorously enforced. however, current legal safeguards may be insufficient. new zealand's experience with rcd indicates it is possible for lay people to illegally import and establish reproducing populations of exotic pathogens. in australia, rcd breached a carefully planned quarantine on an offshore island. unintended establishment and proliferation of engineered viruses may be contained if outbreaks are recognized early, and if proportions of susceptible individuals are removed rapidly from the population either by culling or by immunizing against the pathogen (tyndale-b iscoe, ) . this has never been tried with wild animal populations. the containment of contagious pathogens, such as foot and mouth disease in livestock, indicates such an approach may be possible. highly attenuated forms of myxoma virus are used to protect wild and domestic rabbits in france and the united states, indicating the availability of such technology for this virus at least (fenner & ross, ; tyndale-biscoe, ) . limited field trails with sterilizing microorgansisms are unlikely before (anderson, ). there is abundant evidence that introduced exotic vertebrates that establish feral reproducing populations have disastrous consequences for agriculture and preservation programs for native plants and animals. sources of current vertebrate introductions include sellers and buyers of exotic pets; acclimatization societies that import, establish, and relocate game animals and whose constituents include hunters and fishermen; and farmers and ranchers who import and experiment with novel lifestock (e.g., fitch farming). exotic vertebrates have in some instances great economic importance (as with lifestock and game animals), they also enjoy public popularity because of interest in hunting, fishing, eating, or viewing large and unusual animals in familiar environments. the negative ecological aspects of introduced vertebrates may be poorly understood by the public at large. such limited understanding may hinder control efforts and prevention of importation (bland & temple, ) . legislation has been passed in the united states to minimize risks of importing new and relocating existing vertebrate species. the lacey act passed in and ammended in was enacted to protect certain animals and endangered habitats, and to prevent introduction of noxious pests. under the act, violation of the law can result in fines and imprisonment [see usc w importation or shipment of injurious mammals, birds, fish (including mollusks and crustacea), amphibia, and reptiles; permits, specimens for museums; regulations m for more details]. similar legislation has been developed in new zealand. the biosecurity ( ) and hazardous substances and new organisms (hsno) ( ) acts were devised to protect the environment by preventing or managing the adverse effects of hazardous substances and exotic organisms. campbell ( ) points out that existing laws have many loopholes and are not effective when applied, indicating a need to improve existing regulations and to develop new laws to curtail unwanted entry by alien vertebrates. one proposal is to require importers of exotic organisms to develop "clean lists" and to prove that organisms are not potentially invasive and disrupting to native ecosystems (campbell, ) . legislative approaches limiting imports and exports of organisms may encounter complaints under the general agreement of tariffs and trade (gatt) that stricter quarantine measures are an unacceptable imposition of one country's environmental standards on others (camp-bell, ) . there is an obvious need for greater cooperation among interest groups, scientists, and legislators to devise solutions to problems associated with continuing introductions of exotic species and to provide direction for future action. as an evolutionarily stable control strategy development of resistance (behavioral or physiological) to pesticides (e.g., rodenticides) by vertebrates, and the need for repeated or multiple simultaneous control strategies (e.g., poisoning combined with trapping and hunting) indicate that control of vertebrates is an ongoing endeavor that attempts to reduce agricultural damage and losses (greaves, ) or to protect wilderness areas (cowan, ; morgan et al., ; payton et al., ) from pest damage. biological control has several advantages over chemical and cultural control practices (van driesche & bellows, ) : ( ) it is relatively cheap and biological control programs are often quicker to implement than to develop and to register new pesticides; ( ) use of carefully screened natural enemies increases selectivity of attack toward target pests; ( ) natural enemies in many instances are self-perpetuating and self-distributing; and ( ) development of resistance to natural enemies is extremely rare. one documented case of pests developing resistance to natural enemies is the development of resistance to myxomatosis by rabbits and corresponding attenuation of highly virulent strains of the myxoma virus to strains of intermediate virulence (fenner & ross, ) . the myxoma virusrabbit system in australia and europe is dynamic with increasing rabbit resistance selecting for more virulent strains of virus. this suggests that for the short-term, at least, the system is coupled in an antagonistic coevolutionary arms race (dwyer et al., ) . flexible natural-enemy behavior patterns and physiology have the potential to weaken evolutionary responses that can cause pest resistance to introduced control agents (holt & hochberg, ; jervis, ) . in comparison, pesticides and cultural controls tend to target a fixed physiological or behavioral function or pattern, and the resulting selection regime is constant allowing pests either to increase tolerance to poisons or to learn and develop avoidance behaviors (e.g., bait and trap shyness). spatial heterogeneity of natural-enemy attack limits selection pressure on hosts by natural enemies, thus reducing the rate of resistance development by pests compared with uniformly applied selection pressures such as pesticides. pests that escape attack move into enemy-free areas and continue breeding; thus, the rate of coevolution is reduced by susceptible pests in transient refuges (jervis, ) . at the metapopulation level, natural enemies may be ineffective selection agents because of widespread extinction and establishment of pest subpopulations that maintain pest susceptibility. additionally, resistance development may involve costs leading to a corresponding decrease in fitness. for example, increased tolerance to attack may reduce the pest's reproductive capacity and ability to compete for resources, or may increase susceptibility to other mortality agents (holt & hochberg, ) . there are opportunities to enhance biological control programs against vertebrate pests that cause social, agricultural, and conservation problems. in many instances, biological control offers the best chances for long-term control, particularly in isolated areas with rugged terrain, in suburban areas with high-density human populations, or in places where pests are nocturnal or secretive. biological control will not totally alleviate vertebrate pest problems. it may, however, reduce the vigor of pest populations, thereby reducing damage, minimizing nuisance value, or allowing native species to compete more effectively for food and breeding sites. programs could be initiated to simply reassociate host-specific micro-and macroparasites with pest populations that have depauperate natural-enemy faunas (dobson & may, ) , and there is no shortage of targets as small founding populations of vertebrates continue to invade and proliferate in new habitats. genetically engineered natural enemies are additional tools to aid biological control efforts. research with agents that cause immunocontraception will likely diversify as 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extent of biological control of rats with barn owls, tyto alba javanica in malaysian oil palm plantations. the planter biological control of vertebrate pest effectiveness and cost-efficiency of control of the wild rabbit, oryctolagus cuniculus (l.), by combinations of poisoning, ripping, fumigation, and maintenance fumigation response of wild rabbit populations to imposed sterility development and use of virus-vectored immunocontraception the characters of successful invaders the varying success of invaders biological control of vertebrates--a review, and an assessment of prospects for malaysia observations of the lifecycle of capillaria hepatica (bancroft, ) with a description of the adult acknowledgments i thank vincent d'amico, iii of bean's art ink for preparing the states geological survey provided information on the brown tree snake. key: cord- -bo ui zh authors: shervington, denese o.; richardson, lisa title: mental health framework: coronavirus pandemic in post-katrina new orleans date: - - journal: j inj violence res doi: . /jivr.vo i . sha: doc_id: cord_uid: bo ui zh the united nations office of disaster risk reduction defines disaster risk as the “likelihood of loss of life, injury or destruction and damage from a disaster in a given period, and a product of the complex interactions that generate conditions of exposure, vulnerability and hazard”. racial and ethnic minorities in the united states have been shown to have increased vulnerability and risk to disasters due to links between racism, vulnerability, and economic power, based on disadvantage related to different disaster stages: ) reduced perception of personal disaster risk; ) lack of preparedness; ) reduced access and response to warning systems; ) increased physical impacts due to substandard housing; ) likelihood of poorer psychological outcomes; ) cultural insensitivity on the part of emergency workers; ) marginalization, lower socio-economic status, and less familiarity with support resources leading to protracted recovery; and ) diminished standard of living, job loss, and exacerbated poverty during reconstruction and community rebuilding. moreover, given that psychiatric morbidity is predictable in populations exposed to disasters, mental health and psychosocial support programs should increasingly become a standard part of a humanitarian response. in the crisis and immediate recovery phase of disasters, the focus should be on making survivors feel safe and giving them assistance in decreasing their anxiety by addressing their basic needs and welfare. so, it is critical that governmental institutions, business, and non-profit organizations proactively find mechanisms to work collaboratively and share resources. special attention and extra resources must be directed towards vulnerable and marginalized populations. in this editorial we share lessons learned from experiencing disproportionate impact of health crisis and advocate for the notion that recovery efforts must address trauma at individual, interpersonal and community levels, and be based in a healing justice framework. new orleans' annual mardi gras celebration culminated in the last two weeks of february , with over . million visitors in the city. the first case of covid- was reported on march , and the first death was reported on march . on friday, march , after at least people died due to covidrelated illnesses, the mayor issued a stay-at-home order asking residents to avoid large crowds and to go outside only for essential services. according to the louisiana department of health office of public health, as of march , cases had been reported in louisiana, with deaths. eighteen hundred and thirty-four cases were reported in orleans parish, of which people have died. the city of new orleans has become one of the national epicenters of the covid- pandemic. an article appearing on march in the atlantic entitled, "watch new orleans: with the country's attention turned north, the coronavirus pandemic is exploding in louisiana," journalist van newkirk paints an alarming picture of the public health crisis. approximately % of the u.s. population lives in louisiana, but the state reports % of all covid- deaths, % of all hospitalizations, and % of all positive tests nationwide. the louisiana department of health and hospitals statistics indicate that orleans and jefferson parishes have the highest coronavirus death rates in the country. in orleans parish, there are . covid- deaths for every , residents, and . for jefferson parish. by comparison, both parishes have significantly higher death rates than king county, in seattle, which reports . deaths for every , residents and new york city that reports . deaths for every , residents. the united nations office of disaster risk reduction defines disaster risk as the "likelihood of loss of life, injury or destruction and damage from a disaster in a given period, and a product of the complex interactions that generate conditions of exposure, vulnerability and hazard". racial and ethnic minorities in the united states have been shown to have increased vulnerability and risk to disasters due to links between racism, vulnerability, and economic power, based on disadvantage in each of the eight disaster stages: ) reduced perception of personal disaster risk; ) lack of preparedness; ) reduced access and response to warning systems; ) increased physical impacts due to substandard housing; ) likelihood of poorer psychological outcomes; ) cultural insensitivity on the part of emergency workers; ) marginalization, lower socio-economic status, and less familiarity with support resources leading to protracted recovery; and ) diminished standard of living, job loss, and exacerbated poverty during reconstruction and community rebuilding. the new orleans data center has highlighted that the disparate severity of covid- in orleans parish can be attributed to a long history of racial inequities and socioeconomic disadvantages. the report went on to highlight various inequities, inequalities, and disparities, due largely to race and socio-economic status: ) compared to other hotspots, new orleans has higher poverty rates and lower average incomes; ) nearly in new orleans households do not have access to a vehicle, making drive-up testing close to impossible; ) twenty two percent of new orleanians have no access to internet, including smart phones; ) new orleans adults suffer from high blood pressure, diabetes, chronic kidney disease, and other preexisting conditions at rates higher than in seattle, new rochelle, or new york city. the impact of covid- is further amplified by the well-documented legacy of institutional racism and stark economic and health inequities, including limited access to quality healthcare. the high prevalence of the pre-existing conditions that put people at risk for serious complications from the coronavirus reflect the outcomes associated with negative social determinants of health. disasters reflect an encounter between a hazardous force (in this case the coronavirus) and a human population in harm's way which, within the ecological context, can create demands that exceed the coping capacity of the affected community. a disaster's forces of harm (loss and change) are a complex interplay of the interrelationship and interdependence of social and ecological factors-the individual/family context, the community context, and the societal/structural context. new orleans, nearly years ago, experienced a major disaster. on august , , hurricane katrina struck america's gulf coast. katrina was the deadliest hurricane in seven decades to hit the united states, bringing severe winds and record rainfall into new orleans for a -hour period. two days of intense storm surge damaged the city's pumping system, rendering it incapable of draining the rising water as major floodwalls failed along multiple city wa-terways. as a result, % of the city flooded, and homes, communities, and the urban infrastructure were destroyed. for weeks, the city was submerged in floodwaters as high as five meters, which resulted in extensive structural damage. service delivery was brought to a standstill, and emergency and rescue efforts were severely hampered. more than , people were evacuated, and a minimum of people died from storm-related causes. , in , the national weather service estimated that there was at least $ billion dollars in property damage from hurricane katrina, making it the costliest natural disaster in u.s. history at that time. a survey conducted two months post-katrina by the centers for disease control and prevention and the louisiana office of mental health found that % of those sampled were suffering from ptsd. a longitudinal survey of adult gulf coast residents (n= ) who were directly affected by hurricane katrina found the prevalence of ptsd six months post-katrina was twice as high as the prevalence estimates for the population in the years prior to the hurricane. in this study, poor, racial and ethnic minorities and those with fewer years of formal education more commonly reported stressful experiences postevacuation. notably, ptsd symptomatology was most common among those who lived in new orleans- . % of these respondents reported nightmares, . % reported being jumpier or startled more easily, and . % reported being more irritable or angry than usual. the follow-up survey conducted a year later found that anxiety or mood disorders persisted and increased slightly from . % to . %, and the prevalence of ptsd had almost doubled among those residents who remained displaced. similarly, suicidality was significantly higher with regard to suicidal ideation and suicide plans. a longitudinal study of low-income african american mothers pre-and post-katrina found that even though symptoms of post-traumatic stress disorder (ptsd) declined over time after the hurricane, they remained high- % of the sample showed scores suggesting continued symptoms of ptsd - months after the hurricane. the study also found that there was in increase in psychological distress from % pre-katrina to % - months after the hurricane. home damage was an important predictor of chronic symptoms of ptsd. these data differ from the typical post-disaster circumstances where mental disorders significantly decrease with time and up to % typically resolve within a year. for example, the dou-bling of ptsd levels noted two months after the september attacks returned to baseline - months later. these data illustrate the more severe adverse psychological effects of hurricane katrina compared to other disasters and emphasize the disproportionate mental health impacts of disasters on socio-economically disadvantaged racial and ethnic minority groups. a survey conducted by the institute of women and ethnic studies (iwes) in with adult african american katrina evacuees who had returned to new orleans within two years of the hurricane revealed that % reported irritability and depression, % reported appetite changes, % reported sleep disturbances, and % reported difficulty concentrating. regarding symptoms of ptsd, % reported flashbacks, % reported avoidance of stimuli, and % reported startling more easily. since , iwes has assessed youth for symptoms of ptsd and depression based on criteria from the american psychiatric association's diagnostic and statistical manual fifth edition and screened youth for exposure to violence and worries about their basic needs. close to years post-katrina, psychosocial screenings show an extremely high prevalence of traumatic stress and mental health disorder symptoms among youth aged - in new orleans. of the youth surveyed thus far, % endorse symptoms of depression; % endorse symptoms of lifetime ptsd with % endorsing symptoms of current ptsd; % report exposure to domestic violence; % report having lost a family member or someone close to murder; and % worry about not being loved. of note, the national prevalence rate for adolescent ptsd is % while the rate for depression is %. unlike disasters that are land-based, visually apparent, and time-bound-hurricanes, fires, earthquakes, tornadoes, flooding, and wind/sand storms-this disaster is silent, unseen, and highly unpredictable, and at this point there is no way of determining when the pandemic will end. this uncertainty and unpredictability about the spread of covid- and its impact has created significant emotional distress. a recent poll by the american psychiatric association conducted march - , found that a significant number of americans ( %) are anxious about the possibility of family and loved ones contracting covid- . the survey also found that % of americans report that the coronavirus is having a serious impact on their mental health, with % reporting that the virus is having a significant impact on their day-to-day lives. over % are worried about running out of food, medicine and/or supplies, and % worry that the virus will have a significant impact on their finances. it should be anticipated that mental health needs in new orleans during and after the coronavirus crisis will be significant and may be greater than in other us cities, given higher baseline (katrina-related) levels of trauma-based conditions. additionally, as has occurred globally, it is expected that frontline healthcare providers, at greatest risk for contagion from the virus, will be at great risk of developing unfavorable mental health outcomes. those who experience catastrophic events show a wide range of reactions: some suffer only worries and bad memories that fade with emotional support and the passage of time; others are more deeply affected and experience long-term problems-ptsd, depression, generalized anxiety disorders, and substance use disorders are the most common post trauma psychiatric sequelae. a systematic review of posttraumatic stress disorders following disasters in the past three decades concluded that the burden of ptsd among people exposed to disasters is substantial and is correlated with factors such as sociodemographic and background factors, event exposure, social support, and personality traits. in a february blog, the american psychiatric association committee on psychiatric dimensions noted that adverse psychological and behavioral responses to infectious disease outbreaks are common and include insomnia, reduced feelings of safety, scapegoating, increased use of alcohol and tobacco, somatic symptoms (physical symptoms) such as lack of energy and general aches and pains), and increased use of medical resources. given that psychiatric morbidity is predictable in populations exposed to disasters, mental health and psychosocial support programs should increasingly become a standard part of a humanitarian response. a global panel of experts on disaster and mass violence identified five key intervention principles that should be used to guide and inform intervention and prevention efforts at the early to midterm stages of the event. these principles are: ) promote a sense of safety; ) promote calm; ) promote a sense of self-and collective efficacy; ) promote connectedness; and ) promote hope. these principles were empirically found to restore social and behavioral functioning after disasters. in the crisis and immediate recovery phase of disdisasters, the focus should be on making survivors feel safe and giving them assistance in decreasing their anxiety by addressing their basic needs and welfare. in the lessons learned after the fireworks disaster in enschede, netherlands, soon after a disaster, survivors must be helped to regain their autonomy, reserving clinical psychiatric help for those exhibiting dissociative symptoms or those with prolonged mental health symptoms that showed no improvement after two months. similarly, the world health organization's guidance (june ) regarding mental health in emergencies advises.  strengthen community self-help and social support  offer psychological first aid-first-line emotional and practical support  assure basic mental health care for priority conditions (e.g. depression, psychotic disorders, epilepsy, substance use disorder, etc.) is provided at every health-care facility by trained and supervised general health staff)  provide psychological interventions offered by specialists, trained in trauma-focused approaches, for people impaired by prolonged distress  protect and promote the rights of people with severe mental health conditions and psychosocial disabilities  create links and referral mechanisms between mental health specialists, general health-care providers, community-based support, and other services (e.g. schools, social services, and emergency relief services such as those providing food, water, and housing/shelter) the national child traumatic stress network and the national center recommend psychological first aid (pfa) for ptsd when providing early assistance within days or weeks following an event. pfa is an evidence-informed modular approach to help children, adolescents, adults, and families in the immediate aftermath of disaster and terrorism. pfa is designed to reduce the initial distress caused by traumatic events and to foster short-and long-term adaptive functioning and coping. the core objectives are listed in table . in response to the current viral pandemic, the following strategic activities are being recommended based on local adaption to the aforementioned global and national frameworks, as well as lessons learned from hurricane katrina: to respond to contacts initiated by survivors or to initiate contacts in a non-intrusive, compassionate, and helpful manner. to enhance immediate and ongoing safety and provide physical and emotional comfort. to calm and orient emotionally overwhelmed or disoriented survivors. to identify immediate needs and concerns, gather additional information, and tailor psychological first aid interventions. to offer practical help to survivors in addressing immediate needs and concerns. to offer practical help to survivors in addressing immediate needs and concerns. to provide information about stress reactions and coping to reduce distress and promote adaptive functioning . linkage with collaborative services to link survivors with available services needed at the time or in the future. . support organizations/institutions addressing basic needs (food, housing, finances) and access to healthcare . promote physical safety in the population at large a. provide education regarding coronavirus transmission and steps to prevent transmission and dispel myths b. provide education regarding when to seek testing and/or hospital services . promote psychological safety through virtual/digital and social media; traditional media-print, radio, tv, and billboards: a. provide normalizing psycho-education regarding fear, anxiety, and mood disturbances (normal response to the threat of harm from virus) b. create virtual connection and community to enhance individual and collective efficacy, interpersonal learning, and hopefulness/optimism c. teach calming and coping mechanisms for the general population and targeted populations (medical providers, teachers, new parents, cbos) i. deep breathing ii. mindfulness meditation iii. overall wellness and self-care affirmations . assure access to tele-health resources and medication for residents with existing or newly acquired serious mental health disorders . conduct a rapid assessment of community knowledge, attitudes, beliefs, and actions regarding coronavirus. . prepare mental health systems (public and private) to provide culturally-proficient trauma-based services for children, adolescents, and adults . conduct research to assess level of traumabased disorders . conduct trainings at multiple levels in educational system to assist schools in being able to realize, recognize, and respond to increased levels of trauma conditions in students -i.e. assist schools in adopting trauma-informed and restorative practices . increase access to mental health servicescommunity and school-based with hurricane katrina, widespread assessment of disaster response and recovery efforts emphasized the lack of effective leadership within the federal emergency management agency which, under the authorization of the u.s. department of homeland security, coordinates communications across federal agencies in response to disasters. the inadequate rescue and failed governmental response to the disaster was decried by human rights experts as "shocking, a gross violation of human rights". a select bipartisan committee of the u.s. house of representatives investigating the hurricane cited failures at all levels of government. the report, "a failure of initiative," noted that medical care and evacuations suffered from a lack of advance preparations, inadequate communications, and inadequate coordination, and that the failure of complete evacuations led to preventable deaths, great suffering, and further delays in relief. the impact that the virus will have on the city will inevitably conjure memories of katrina for many new orleanians. covid- will affect every aspect of life. its predicted force is akin to a tsunami: a devastating eruption generating a series of progressive waves that sweep across the land in ever-widening circles. so as to never repeat the failures of hurricane katrina, it is critical that governmental institutions, business, and non-profit organizations proactively find mechanisms to work collaboratively and share resources. special attention and extra resources must be directed towards vulnerable and marginalized populations. for example, children that were born into and lived through the aftermath of katrina continue to show emotional distress nearly years after the disaster. the trauma caused by this public health crisis will be carried and embodied for the longest time by the youth that are living through it. meaningful action must be taken immediately to mitigate the possible devastating impact of this virus on the youth of new orleans. experts are calling for wide-ranging federal action including direct payments to families during this crisis, a national moratorium on rent and eviction, additional support for the homeless, and emergency resources for children in foster care. vann newkirk's march , article in the atlantic, "the kids aren't all right", focuses on the trauma and long-term economic impact that the crisis will have on children. newkirk interviewed bruce lesley, the president of first focus on children, who is advocating for an expansion of the supplemental nutrition assis-tance program (snap), and alice fothergill, who coauthored "children of katrina" with lori peek. fothergill spent seven years studying the effects of katrina on young people and found that existing social disadvantages, in this case poverty and race, fueled an uneven recovery among kids based on their socio-economic circumstances. she noted, "disasters last a really long time in the lives of children. people are talking about vulnerability, but they are not talking about children at all." as dr. shervington has advised on billboards throughout the city of new orleans in the years post-katrina as youth violence began to spike, 'untreated trauma is the underbelly of violence'. the covid- pandemic now grips new orleans in another disaster. we have learned that response and recovery efforts must address trauma at individual, interpersonal and community levels, and be based in a healing justice framework, as outlined in iwes' publication, healing is the revolution. united nations international strategy for disaster reduction race, ethnicity and disasters in the united states: a review of the literature monitoring the covid- pandemic in new orleans and louisiana textbook of disaster psychiatry hurricane katrina: facts, damage and aftermath control cfd, prevention. surveillance for illness and injury after hurricane katrina--three counties overview of baseline survey results: hurricane katrina community advisory group five years later: recovery from post traumatic stress and psychological distress among low-income mothers affected by hurricane katrina post-traumatic stress disorder following disasters: a systematic review mental health in new york city after the september terrorist attacks: results from two population surveys no one is coming to save us: coping with the stressful aftermath of katrina american psychiatric association. diagnostic and statistical manual of mental disorders prevalence, persistence, and sociodemographic correlates of dsm-iv disorders in the national comorbidity survey replication adolescent supplement. arch gen psychiatry factors associated with mental health outcomes among health care workers exposed to coronavirus disease the epidemiology of post-traumatic stress disorder after disasters committee on psychiatric dimensions of disasters. psychiatry.org/news-room/apa-blogs/apa-blog , accessed evidence-based mental health and psychosocial support in humanitarian settings: gaps and opportunities. evi-dencebased mental health five essential elements of immediate and mid-term mass trauma intervention: empirical evidence. psychiatry mental health services required after disasters: leaning from the lasting effects of disasters mental health center in post-disaster recovery: ten-year retrospective of mediant's work in enschede, netherlands national child traumatic stress network and national center for ptsd poverty expert finds new orleans 'shocking select bipartisan committee to investigate the preparation for and response to hurricane katrina. a failure of initiative the kids aren't all right healing is the revolution. institute of women and ethnic studies competing interests: none declared. ethical approval: not required. key: cord- - xgpvxax authors: messing, emily g; quinn, nicholas j; shah, dhara d; veltri, keith; chirico, jacqueline title: practicing during a pandemic: the role of a new pharmacy practitioner date: - - journal: am j health syst pharm doi: . /ajhp/zxaa sha: doc_id: cord_uid: xgpvxax in an effort to expedite the publication of articles related to the covid- pandemic, ajhp is posting these manuscripts online as soon as possible after acceptance. accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. these manuscripts are not the final version of record and will be replaced with the final article (formatted per ajhp style and proofed by the authors) at a later time. w hen transitioning from pharmacy resident to clinical pharmacist specialist, there are many challenges and uncertainties that one might face. from answering complex clinical and operational questions to finding your place on the interdisciplinary care team and defining your own career path, as a new practitioner you may experience uncertainty without preceptors to oversee and guide you. however, most practitioners are not fully prepared to practice during a pandemic soon after completing postgraduate training. while students and residents may be introduced to the concept of emergency preparedness in pharmacy school and throughout residency, nothing can fully prepare a new practitioner for the experience of being involved in management of a crisis such as the coronavirus disease (covid- ) pandemic. while there is published literature that describes the role of the pharmacist in a pandemic, it is mainly limited to outpatient pharmacy practice and past pandemics, such as the novel h n influenza outbreak. additionally, recent publications regarding the pharmacy profession's response to the covid- crisis are often generalized to pharmacists at various stages of their careers, and there are limited resources that emphasize the role of the new practitioner in emergency preparedness. the purpose of this article is to describe the unique roles that new practitioners can serve on a disaster response team. the scenarios discussed below are based on the experiences of new practitioners in a large, urban academic medical center located in new york city, the epicenter of the initial phase of the covid- pandemic in the united states. finding your place. health systems and institutions have handled the covid- pandemic in different ways, with many decisions having to be made rapidly by hospital leaderships. this dynamic can apply in any pandemic. within a pharmacy department, it is crucial to quickly establish daily calls with operations, clinical, and purchasing teams across the health system to share information and make decisions. these decisions pertain to repurposing space within hospitals to open new units, redeploying provider teams to treat critically ill patients, and creating new treatment guidelines with little or no evidence to serve as a guide. being included in decision-making processes can provide new practitioners the opportunity to take the lead on many initiatives and apply the necessary skill sets acquired during residency to real-life practice. the typical command structure during emergencies tends to follow the day-to-day hierarchical structure of the department: director, assistant directors, managers, pharmacists, and technicians. information is disseminated down hierarchy so that everyone is appropriately and routinely informed. residents, as well as new practitioners, can align with this structure in a variety of ways, such as by working with operational managers to open new units and retrieve medications to stock medication rooms and assisting clinical managers with literature reviews to create medication-use guidelines. they can even support directors with the various miscellaneous tasks that need to be accomplished. ultimately, the most important means for new practitioners to find their place in the departmental structure is by being flexible and attuned to all operational, clinical, or systems-based opportunities that arise. for a new practitioner, major challenges early in professional practice can cause insurmountable fear, apprehension, and uncertainty. it is easy to fall victim to impostor syndrome, described as "a collection of feelings of inadequacy that persist despite evident success." affected individuals suffer from feelings of "being unable to internalize and accept personal success without feeling like these accomplishments are due to luck rather than ability." many of the techniques used to overcome impostor syndrome can also be applied in a pandemic situation. these involve focusing on improving one's strengths, asking mentors for professional feedback, and acknowledging previous successes to tackle new challenges. managing operations during a pandemic. starting as a new pharmacy manager after completing a residency entails additional challenges that other new practitioners may not face. these challenges include making the transition from preceptor oversight and self-management to supervising other members of the department and establishing oneself as a leader at a new institution. when working as a new practitioner in a pharmacy administrative position, it is important to always call on department directors, senior members of the hospital leadership, and other pharmacy advisors within your mentor network for guidance. taking advantage of these resources can provide enormous insight and can be helpful when addressing some of the unintended consequences that may arise from opening new inpatient units in the absence of additional pharmacy support. pharmacist burnout, increased staff requests to use sick days, and drug shortages can be common, and looking to others for guidance on how to manage these issues can be beneficial. for example, if staff shortages arise, an option is to pull back on unit-based pharmacy services to provide centralized pharmacy coverage. if drug shortages occur, work with clinical staff to develop backup protocols and explore other therapeutic alternatives with the purchasing team. finally, communicating these changes to frontline pharmacists to ensure that they are given the opportunity to pose any questions or suggestions is of the utmost importance. given the overall anxiety of caring for patients in a pandemic or other crisis situation, it is crucial to lead by example. additionally, it is important to emphasize the mentality that no job is too small and every role is valuable in keeping the department running. this sense of teamwork can make an immeasurable difference, and it can be a big help when morale is low. working alongside staff members and creating a safe space for them to voice concerns allows the pharmacy team to become comfortable with being uncomfortable so that a "new normal" can be established. managing clinical practice during a pandemic. while the pharmacy operations team works to establish a new normal and find new ways to tackle the unprecedented challenges posed by a pandemic situation, the clinical pharmacists must also adjust their practices to meet patient care demands, including practices to ensure safe and effective medication use. it is crucial to establish a tangible action plan; however, it is important to remember that alternate strategies may be required if systems to curb inappropriate drug utilization are not adequate. a first step to address this challenge could be to create a priority list of medications commonly used in treatment of patients with covid- , including analgesics, sedatives, neuromuscular blocking agents, vasopressors, and electrolyte preparations. additionally, it is critical to work with purchasers and operational managers to prepare for the inevitable shortages in medications and to guide them towards appropriate alternatives. it may be difficult to illustrate the necessity of having critical care medications available while the focus is on antivirals and other experimental treatments. however, treatment guidelines can be used to reinforce the utmost necessity of supportive care. in situations where supportive care is a top priority, in conjunction with a rapid rise in the number of admitted patients, protocolization of care becomes a necessity. this is especially true when hospitalists unfamiliar with critical care medicine will likely be tasked with caring for mechanically ventilated patients. moreover, the use of supportive care may be limited by institutional guidelines prohibiting the use of certain medications outside of an intensive care unit (icu) due to lack of proper monitoring and supervision. despite these restrictions, sedative use at the authors' institution rose over % during the early weeks of the covid- crisis; despite the pharmacy department providing proper initial guidance on appropriate usage, medication shortages became inevitable. it is essential for new practitioners who have established relationships with the medical teams to develop procedural protocols that outline the processes for an-algesia and sedation in general medical units. for instance, clinical pharmacists can emphasize the use of oral agents and bolus dosing to wean infusions and prevent inappropriate oversedation. such actions can help minimize medication waste, conserve drugs in scarce supply, and ensure that patients are safely treated using evidence-based practices. regarding appropriate care of patients infected with a novel virus, it is important to be cognizant of original research published at a rapid pace, which may result in the development and dissemination of protocols within the health system without intensive review or discussion. specifically, policies not involving input by the pharmacy department can often overlook certain patient factors, including organ dysfunction, the need for weight-based dosing adjustments, and drug interactions. a multidisciplinary approach, especially during a pandemic situation, should be employed to ensure that there is an established and standardized process in place for development, approval, and dissemination of new policies and procedures. one approach is to require that all new protocols established during a pandemic be vetted by the institution's pharmacy and therapeutics committee before being introduced into practice. with the possibility of the adult census within an institution exceeding bed capacity during a pandemic situation, it is important to look to personnel on other units and floors to extend care and assist. examples of units that can be quickly transformed to admit adult patients include general pediatrics floors, pediatric step-down units, and icus of an affiliated children's hospital. , it is imperative for a new practitioner to work with adult and pediatric intensivists, hospitalists, nurses, and other pharmacists to ensure that such converted units are adequately supplied to expand pediatric services to adult patients. it is crucial to optimize automated dispensing cabinets by stocking medications commonly used in adult patients, including those required for advanced cardiac life support, rapid sequence intubation, and postintubation management. this can be achieved by creating an extensive checklist of medications that could be used in any of the above scenarios. finally, it is necessary to develop a materials checklist that incorporates protocols ensuring that converted units have an adequate supply of cardiac monitors, adult blood pressure cuffs, intravenous (iv) poles, and tubing for iv medications. with critically ill adult patients being admitted to a children's hospital, pediatric teams will be required to manage adult patients. a new practitioner can help prepare the clinician teams for this scenario by providing education, clinical pearls, and treatment algorithms to pediatric pharmacists, nurses, medical residents, hospitalists, and intensivists. additionally, although adult providers are familiar with caring for adult patients, they may also be required to treat patients outside of their practice specialty throughout the institution. new practitioners can facilitate such transitions by giving lectures to hospitalists shadowing icu rounds on topics such as analgesia and sedation or by publishing information on the health system's network. once education has been provided, new practitioners can run reports on targeted medication therapies using the electronic medical record to track and assess for appropriate use of sedatives, analgesics, paralytics, and vasopressors; this can allow pharmacists to "identify and intervene" on units that may be struggling with evidence-based therapies and to provide a venue to identify candidates for active clinical trials. lastly, it can be expected that there will be an increase in the number of code calls and rapid responses, and a new practitioner can play a valuable role in these emergent situations. this roles includes but is not limited to drawing up medications into syringes, priming tubing for medication infusions, and setting up the iv infusion pumps, all of which are skills practiced during residency training. additionally, new practitioners can further solidify their essential role on the patient care team by assisting residents and hospitalists with ordering medications that were administered during intubations and/ or cardiac arrests. furthermore, the new practitioner can play a pivotal role in the care of a patient who does not receive an icu bed for hours and, as a result, for whom postintubation and/or cardiac arrest care has to be started on the general medicine floor. in such cases a new practitioner can educate the nurses on the proper administration of critical care medications and ensure that appropriate patient monitoring is implemented. managing informatics systems during a pandemic. as operational and clinical workflows quickly change in response to a pandemic, it is crucial that the informatics systems used within the institution are updated to reflect the most up-todate treatment protocols. these changes are required so that patient safety is not compromised and can be accomplished through active communication and teamwork among pharmacy, informatics technology, medicine, and nursing teams. new practitioners can put their residency training into action by applying their recently acquired and extensive knowledge in critically evaluating literature for applicability to a specific patient population. this can be especially valuable in a time when changes are required at a rapid pace and there is very little available literature to help guide practice. new practitioners can contribute to the team by evaluating a requested change to practice, which will also require subsequent changes to the systems and can help prioritize these needs. another strength that new practitioners possess is that their residency training likely taught them to view informatics systems as a whole. they understand the entire workflow-from the moment the medication is requested and verified in the electronic medical record to the time of preparation in the pharmacy using the iv workflow system and, finally, administration by smart infusion pump. this knowledge is essential when validating all requested changes to informatics systems to ensure that each system is updated correctly while promoting safe patient care. this task can be accomplished by using tools taught during residency. examples include developing checklists to make sure that no system or step along the way is missed and maintaining open communication between the pharmacy and providers. another example is assessment of systems for possible risk points by performing informal failure mode and effects analyses for new medications and/or concentrations introduced into practice. ultimately, informatics systems will be used to support all clinical and operational activities within the institution, and new practitioners can play a valuable role in ensuring the safety and accuracy of the systems. closing notes. the transition from pharmacy resident to clinical pharmacy specialist comes with its own set of unique challenges under normal circumstances, and it can be even more demanding during times of uncertainty. while practicing during a pandemic is hopefully a once-in-a-lifetime experience, it is imperative that residency programs incorporate more emergency response training into their curriculums. this training can include emergency response simulations, literature reviews, and discussions on past pandemic responses, as well as active involvement in an institution's emergency preparedness committee. new practitioners have a vast array of previously developed skill sets, including communication, active listening, teamwork, decision-making, clinical knowledge, and flexibility. despite these skills, new practitioners may still doubt their own abilities; however, they should be confident in their training and never overlook their mentor network. it is important for them to rely on leaders within their institutions for guidance but also remember that they are leaders themselves. by doing so, they can establish themselves as essential members of the emergency response team by following the chain of command. knowing when to ask for help is another important attribute that new practitioners should not forget, especially during a time of instability and uncertainty. while new practitioners have a wealth of knowledge gained from residency training, their colleagues have more practical experience. the additional proficiencies that seasoned practitioners bring, coupled with new practitioners' extensive and diverse training experiences, can contribute to the development of a well-rounded patient care team. defining the pharmacist role in the pandemic outbreak of novel h n influenza on the frontline against covid- : community pharmacists' contribution during a public health crisis. res social adm pharm pharmacy emergency preparedness and response (pepr): a proposed framework for expanding pharmacy professionals' roles and contributions to emergency preparedness and response during the covid- pandemic and beyond. res social adm pharm bronx emerges as new york city's new epicenter feeling like a fraud? american psychological association overcoming the impostor syndrome hospital pharmacists' pharmaceutical care for hospitalized patients with covid- : recommendations and guidance from clinical experience. res social adm pharm surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease (covid- ) repurposing a pediatric icu for adults rapid implementation of an adult coronavirus disease unit in a children's hospital key: cord- - jo y b authors: ridzi, frank; prior, trina title: community leadership through conversations and coordination: the role of local surveys in community foundation run community indicators projects date: - - journal: int doi: . /s - - -z sha: doc_id: cord_uid: jo y b community indicators (ci) projects rely on a variety of sources for the data that they make available to measure community well-being. while statistics collected and distributed by national and local governments are perhaps the most prevalent, some communities in both canada and the united states have found great advantages to commissioning or administering their own surveys of local community members in order to enhance the insights that government-curated data can provide. in this paper we examine two organizations engaged with indicator projects that have opted to do so from the perspectives of their primary ci project supporters: the vancouver foundation in canada and the central new york community foundation in the united states. among the advantages explored are increased capacity in key community leadership elements of: engaging residents, working across sectors, commissioning and disseminating local data and research, shaping public policy, and marshaling resources. we conclude by reflecting on the many synergies between the ci and community foundation (cf) movements, paying attention to their shared interests in community well-being through better conversations and coordination among the organizations in the communities they serve. community well-being is a multifaceted and interdisciplinary concept that invites a variety of frameworks as well as industry sectors to participate in its study and improvement (phillips and lee ) . while a shared definition may be elusive, two key dimensions have helped to give shape to this growing field of study: . indicators used to measure community well-being (sung and phillips ) and . action being taken by local community members and anchor institutions to improve community well-being (sirgy ) . in the following pages we explore how two international movements, the community indicators (ci) movement and the community foundation (cf) movement, have characteristics that naturally position them to contribute to our understanding and improvement of community well-being. we then review how both movements have experienced increasing focus on local community well-being -ci increasingly focusing on localized data and cfs increasingly focusing on their deep knowledge of and ability to effectively take action to improve local communities. to further explore this increasing interest in local data and knowledge about community well-being, we then turn to two case studies where these movements have joined forces in the form of cf led ci projects, one in canada and one in the united states. we first provide context on the origin and development of these cf initiated ci projects before examining how their reliance on federally funded, and publicly available, data about their local communities proved insufficient to address the desire for knowledge about their local communities' well-being. we then profile innovative solutions to this problem and the new opportunities and capabilities local survey initiatives have created. community well-being is a multifaceted concept that revolves around place and geography. it has historically been articulated in a variety of ways but often includes economic, social and physical community dimensions (sirgy ) . though hard to define, there is general consensus that community well-being involves many interconnected parts that make it complex and hence well suited to interdisciplinary study in fields such as geography, sociology, political science and environmental and cultural studies (phillips and lee ) . this has led to broad conceptualizations such as kee et al.'s ( ) multidimensional model that includes the following six types of capital that a community can possess: human, economic, natural, infrastructure, cultural, and social (lee and kim ) . regardless of the dimensions included, community wellbeing is defined by the word "community" which typically refers to a specific local geography such as a city or town (phillips and lee ) . in addition to referencing a specific geography, two things that have historically been helpful in defining community well-being are: . indicators and . action. as we will explore in the future pages, both are points of synergy between the cf and ci movements. in the field of community well-being, indicators have been valued for their usefulness in "conceptualizing and assessing community wellbeing" (sung and phillips ) . it is not until we begin to try to measure whether a community's well-being is high or low that we are faced with the many possible approaches we can take. indicators help us translate our theoretical ideas into concrete, operational terms and force a degree of pragmatism on the study of well-being. after all, if well-being cannot be measured it is difficult to study using the standard tools of social science. the result is a robust literature on indicators of community well-being that is guided by such theoretical perspectives as "socio-economic development, personal utility, just society, human development, sustainability, and functioning" (sirgy : , ridzi et al. . rather than an afterthought, indicators and quality of life have evolved as intertwined concepts with some tracing the concept of quality of life and well-being itself to the us "social indicators movement" of the s (lee and kim : ) . the goal of taking action to improve the well-being is another defining characteristic of the field of well-being studies. this is a goal as well for the ci movement (and as we shall see of the cf movement) but it is also part of a symbiotic relationship such that in the words of sirgy ( ) "many community conditions are outcomes of community action (p. )." hence action (or inaction as the case may be) is in many ways implied in the notion of indicators. nevertheless, making the connection between indicators and action is itself a defining feature of the field as well-being and quality of life studies scholars have increasingly called for stronger connections between well-being studies and action in such forms as public policy (lee and kim ) . this is another way in which well-being and indicators are interwoven. as warner ( ) has pointed out, "a common thread among different indicator projects is the desire to find the right measures to influence policy and action (p. )." the increasing focus on connecting the study of well-being with indicators-style measurement and action is most visible at the local level (lee and kim ) . some examples include community indicators victoria (australia), jacksonville indicators (united states), sustainable seattle (united states), calgary indices of community well-being (canada), and the world bank's city indicators project (lee and kim ) . warner ( ) provides some further context to this local push for indicators and action by chronicling how the common frameworks that dominated quality of life studies (sustainability, healthy community, and government benchmarking) were augmented in the early s with a more subjective approach to well-being in such forms as questions of happiness and public happiness. this focus on measures of subjective well-being opened the door to collecting data beyond typically collected and reported census-style data and government administrative records. as sirgy ( ) has pointed out, ci projects seeking to capture residents' perception (such as happiness) and to assess the condition of community services have been forced to resort to community surveys. while requiring greater investment of local resources, it plays into one of the strengths of cis in its emphasis on the local. as warner has argued ( ), "from inception, the greatest strength of the community indicators movement was perhaps the ability to hyper-localize measures of community well-being (p. )." in this increasing emphasis on the advantages of local focus and data granularity we see a parallel with the community foundation movement. what has been referred to as the "community foundation movement" (harrow et al. ; sacks , community foundation atlas ) is a parallel trend to the ci movement that has also occurred internationally (but with a large contingency in the united states and canada). the cf movement focuses on action to improve community well-being. recent years have seen growth in a variety of place-based funders (in the united states and globally) (harrow et al. ; mazany and perry : ) but cfs in particular have seen such massive expansion that nearly % of those that exist today were created in the last years (leonard : ) . though cfs are known to play a variety of roles including investor, convener, partner, and supporter (philipp and traylor : ) , they can fundamentally be understood as charitable mechanisms designed, "to promote sustained community-based philanthropy and to address changing local needs (walkenhorst : )." they do this mainly by soliciting donations, managing bequests and generally serving as a community's permanent charitable endowment that exists to invest donations wisely and using a prudent spending rate. earnings are then reinvested back into the community through funding nonprofits to do work ranging from the arts and human services to animal welfare and environmental stewardship. dating back to the cf movement in the united states has prospered from changes in tax laws that have given them advantages over private foundations and allowed for the proliferation of donor-advised funds (harrow et al. ; carson : ; leonard : ) . the popularity of donor-advised funds effectively shifted the audience and accountability structure of cfs such that the majority of their business was living donors by the s (leonard : ) . this not only helped to drastically increase the number and size of cfs, but it also placed them in competition with forprofit financial sector products such as those offered by fidelity investments which allowed financial planners to also offer to help charity-minded citizens make donations back to their communities (ballard , leonard . as competition increased, cfs increasingly sought to articulate their market advantage as a profoundly more intimate knowledge of the local communities they serve (harrow et al. ; mazany and perry ; ballard ) . a key part of this is a nuanced sensibility about the local needs and assets that together bring about the community's well-being and quality of life. community foundations have expressed that they have a 'finger on the pulse' of the local community in a variety of ways including the use of ci to monitor changes in community well-being in areas such as unemployment or teen pregnancy rates (ranghelli ) . however, one key area in which cfs have increasingly sought to distinguish themselves is in the area of community leadership (cfleads and cfinsights , sacks ). within the cf world, community leadership has taken many forms, but has historically been defined along the lines of: contributing actively to community discourse in a way that better informs the community, building strategic connections that help to broker local solutions to pressing problems, cultivating both donor and governmental resources to maximize funding for local solutions, fostering greater efficiency in problem solving by leveraging systems change through such forms as policy advocacy and greater local collaboration, and championing accountability through measuring impact and increased capacity (ballard ) . this has often translated into such cf activities as: "convening stakeholders around a common problem or issue; forging partnerships that leverage additional public or private resources; brokering new, fragile or even contentious relationships; providing needed training and technical assistance to nonprofits; speaking out and using the media to raise visibility and spur action on an issue; commissioning research and needs assessments to identify gaps in services; and collaboratively creating new institutions (ranghelli : ) ." community foundation community leadership has also been increasingly seen in the area of supporting collective impact efforts to collaboratively address community problems through coordinated, multi-sector and data driven partnerships (ridzi and doughty ; ridzi ) . though cfs as a field have experienced increasing market pressures to move into the community leadership space, and have even been the target of public admonishments to lead, engagement has been inconsistent with less than a third engaging in this way (harrow et al. ) . this is in part due to wide variation in the proportion of discretionary grant making funds across organizations (which results in discrepancies across cfs in terms of their latitude to direct funds toward contemporary needs) (pavey et al. ) . there is also broad interpretation about what is meant by "community leadership" (pavey et al. ) . in some cases, it has meant talking a stand to be a force for civility and progress amid political chaos. this is the case with the community foundation for northern ireland, which focused on peace building by gaining the respect of different sectarian constituencies, and with the community foundation for south sinai and the maadi community foundationboth in egyptwhich publicly embraced goals related to revolution (harrow et al. ) . in other cases, community leadership has taken the form of efforts to revitalize chronically disadvantaged communities through "embedded philanthropy" and civic engagement (karlström et al. ). this has been the case with such cfs as the denver foundation and humboldt area foundation in california who have invested heavily in fostering local resident leadership (by funding block parties, neighborhood cleanups and advocacy) and including bipoc representation in economic planning efforts, respectively. in still other cases, such as the london community foundation, community leadership has taken the form of partnering with media (in this case the evening standard news outlet) to launch the dispossessed fund in order to shine a light on issues affecting londoners ranging from food poverty to gang violence to covid- (pavey et al. ; the london community foundation ). another approach to community leadership that has won acceptance in the cf world is that of curating and publishing indicators of community well-being, such as the toronto community foundation's vital signs which serves as a platform for advocacy toward improved services and policy change (harrow et al. ) . seeking to assert themselves as local community leaders with specialized local knowledge and personalized service (leonard ) many cfs have made investments in data infrastructures that reinforce their brand and identity as having a finger on the pulse of community well-being. in taking on this role, is not uncommon for cfs to conduct surveys. for instance, the first cf to come into existence, the cleveland foundation, conducted surveys at its onset related to schools and criminal justice to help set its grantmaking agenda and raise its profile as a leader in the community (sacks ) . more recently, in and , the kalamazoo community foundation surveyed the local community on community issues and philanthropic behavior. in and , the berkshire taconic community foundation launched a resident survey to assess community needs to give local community members the opportunity to provide perspectives "on key challenges and opportunities for improving lives." similarly, in the saint paul and minnesota foundation launched the "east metro resident pulse," a vitality survey of three counties that is conducted every two years. lastly, and perhaps most pertinent to this paper, going back to in canada, the community foundations of canada (cfc) coordinated vital signs reports of existing data (sacks ) , to which some foundations elected to add a survey component. the above literature on the ci and cf movements suggest a growing synergy of shared interests in the well-being of the local communities where they serve. their work is mutually advantageous and inherently compatible because they are both "movements" aimed at improving the local communities they serve through participation of local residents. community indicators and cfs furthermore offer the potential to complement each other's work by identifying issues of community concern and matching funding to address them, respectively. furthermore, both movements have been gravitating toward a more intimate knowledge of their communities. in this respect, the synergy between ci and cfs is visible through their mutual interest in local community surveys. to better understand the appeal of this trend, we present two case studies of cfs using ci and local surveys to focus on community engagement. the program context british columbia is canada's westernmost province, and with . million people, has the country's third highest population (statistics canada). vancouver foundation is canada's largest cf and although named after the city of vancouver, it is a provincial charity. it has been investing in communities since and through its more than endowment funds, has distributed more than $ billion throughout the province to charities in areas such as arts and culture, education, children and youth issues, environment, animal welfare, community health and social development. in addition to being a broad funder, the organization also focuses resources on community-identified initiatives that strengthen residents' connections and engagement in their communities. vancouver foundation works to convene partnerships and conversations around emerging issues, and also through conducting and sharing research. the commitment to learning and sharing knowledge and resources can be seen though its open licensing initiative which allows access to locally relevant and up to date data that can be used by others to identify and address the opportunities, issues and urgent needs related to their work. vancouver foundation began its notable ci work in with the national launch of vital signs, a program which originated as a project of the toronto community foundation in the late 's , and is now coordinated nationally by community foundations of canada (cfc). at the onset, the vital signs initiative was designed to focus on existing research from national, regional, government and non-government sources rather than conducting new research. each report contained ten set issue areas, such as affordability, education and safety, with some cfs adding one or two areas specifically relevant to their community. each issue area was then paired with four to ten indicators (patten and lyons ) , with cfc providing cfs with national data sets. on a designated day in the first week of october, participating foundations across canada would collectively launch their local vital signs reports. since its inception, "vital signs has evolved to become more flexible and accessible to a broad range of community foundations" (pole : ) with cfs adapting the format to ensure the best fit for their organization's needs and focus. some have moved away from a comprehensive look at how communities are faring in a range of key quality of life areas in favor of releasing reports focused on a specific issue such as social capital and the creative workforce. other foundations have elected to produce less labor-intensive mini reports or focus strictly on hosting community conversations. most recently, cfc has begun to align national data sets with the un's sustainable development goals (sdgs) which has allowed cfs to measure local canadian data against common indicators as well as in a global context. vital signs reports are designed to provide a comprehensive view of local issues and enhance the ability to make connections between various needs and issues. this allows cfs to work with a wide range of community stakeholders and sectors and is a means by which cfs can fulfill the community leadership aspect of their mission. with vital signs, cfs can play a role of neutral knowledge broker and convener in their community and are uniquely positioned to capitalize on their credibility to shape community discourse and dialogue on local issues (pole ) . while cfc provides access to national data sets, many foundations also elect to complement existing data with a perceptions survey component. these surveys are administered locally by the host cf with many focusing on asking residents, or 'citizen graders', to assign a letter grade, or rating, to each issue area as well as identify top priorities that need to be addressed for the issue area. vancouver foundation released its first report in with a focus on the city of vancouver, an urban area with a population at the time of approximately , ( statistics canada). three additional reports were released in , and with an extended reach of metro vancouver, an area with a population of approximately . million. two special youth issues were released in and . in , the foundation extended the reach of the report to have a provincial focus. the most recent report, released in october , focused on community participation, and also has a provincial focus. although vancouver foundation's first vital signs report in relied heavily on secondary data, the foundation identified at the time that there were a number of frustrations with this approach including: not being able to find recent data; finding that necessary data had not been collected for certain areas of interest; discovering that data were not in a useable format; and issues with public accessibility. these frustrations were not isolated to the vancouver foundation. a report published in on the vital signs program acknowledged the challenge of obtaining sufficient and up-to-date data. as the authors concluded, "ultimately the contents of the reports are circumscribed by what data are available" (patten and lyons : ) . while working with cfc on the foundation's reports, vancouver foundation, in an approach used by other cfs, also collected local data through a research committee. up until the report, survey data focused on assigning letter grades and identifying key areas for improvement, to provide valuable additional information to the report. in , vancouver foundation expanded its vital signs project to a provincial report to better reflect the foundation's geographic reach and to capture broader trends in communities throughout british columbia. due to the challenges of managing the scope of the project,and finding consistent and timely secondary data for both small and large communities, the decision was made to base the report solely on primary research collected through a survey. working with mustel research group, the survey contained three main areas of focus: . community assets, which looked at what people liked best about their community; . issue areas, which explored the issues of greatest concern and opportunity for improvement; and . sense of belonging and community involvement. in addition, there were demographic questions including income, education, type of home/dwelling, ethnicity, personal family situation and years lived in current community to enable robust cross tabulation for vancouver foundation, and those wishing to use the data. in addition to a research committee of local experts, the process of creating the survey was heavily influenced by input and feedback from other cfs, who were expected to be key users of the data. this process ensured it was relevant to, and representative of, the diversity of the province's communities. co-creation also fostered buy-in, which resulted in the majority of the province's cfs helping to distribute the survey ensuring provincial representation in responses. the survey was completed online by close to bc residents between june th and july th, , far surpassing the initial goal of responses. the final sample was weighted to match statistics canada census data on the basis of gender, age, and region of residence. community foundations across british columbia promoted the survey through websites, social media, email, newspaper advertisements and partnership arrangements. these valuable outreach efforts resulted in regional representation that otherwise would not have been possible. approximately % of interviews were collected by mustel group through panels, and % by cfs. respondents could complete the survey in english, chinese, or punjabi in an effort to further increase sample representation. to ensure cfs, and other interested parties, were able to view findings for the communities they serve, respondents were asked to identify where they live based on major centers where foundations are located. respondents from smaller surrounding communities were asked to select the center they live closest to. communities were then grouped into 'regional clusters' based predominately on bc health boundaries. syracuse new york is a medium sized city in the united states with a metropolitan statistical area population of around , . it is the largest city in the central new york region. the central new york community foundation is the region's largest charitable resource. established in , it collects contributions from donors, manages them to grow over time and then distributes funding to local charities to help them thrive. with assets of more than $ million it has invested more than $ million in community improvement projects since its inception. as a grantmaker, civic leader, convener and sponsor of strategic initiatives, the central new york community foundation strives to strengthen local nonprofits, encourage better understanding of the region, and address the most critical issues of our time. syracuse traces its ci work back to when a group of citizens began to have community conversations, collect indicators and track progress (ridzi ) . this effort evolved in when the central new york community foundation launched a new version of ci in a website format, cny vitals (ridzi ) . today the website consists of two components that highlight key community trends in the areas of poverty, education, health, housing, economy and arts and people (or demographics). the first component is a data visualization engine whose construction and maintenance is contracted out to a firm, which routinely updates the database with publicly available statistics from sources such as the united states census bureau, the department of labor and the state departments of health and education. the second component is a website that takes selected data visualizations from the first web engine and embeds them on a more journalistically focused website that seeks to put a human face on the data available in the visualization engine. while both components are available on the internet and appear as companion websites, the visualization engine has a variety of complex permutations for data display options that are more suited to professional data consumers such as grant writers and program developers. the second, more journalistic website is designed for the general public who is seeking to keep tabs on key community trends and are more receptive to a curated interpretation of what these trends mean for people in their everyday lives and why it should matter to the reader. this ci website is one of many that exist across the united states. it is similar in that the majority of data come from federally created sources that are made publicly available on government websites. while the united states census bureau is a robust and essential national asset, when it comes to local community improvement there were several key shortcomings that led the central new york community foundation to invest in greater local data collection infrastructure. first, was the issue of timeliness. as has been noted in other areas of the literature, the open source, free and easily accessible nature of government data comes with a trade-off of being delayed in its collection and availability. sometimes data that are collected are not available for a year or more afterwards. this makes it very difficult for organizations to use these data for planning to address immediate needs, and also difficult to assess whether any progress is made after local cf funded action is taken. furthermore, the audience for federal data is a national one that is satisfied with local estimates that have large margins of error. while this might be acceptable for communities that want to compare themselves with others across the nation, the error ranges are too large for communities that wish to use these data to measure themselves over time. finally, the questions asked in the data collected by national government entities are uniform across the nation and unresponsive to the nuances of local questions for which community members are seeking answers. it is simply infeasible to expect federal data collection authorities to tweak their surveys and census mechanisms to more precisely probe the issues that are on the minds of today's central new yorkers. overdependence on publicly available data sources was a sense of frustration for residents of the syracuse area. the community was able to identify where they were doing worse than other communities but not able to drill down to the specific sub parts or neighborhoods in the community to see what was going on at a more granular level. as a result, initiatives had major blind spots when it came to trying to deploy such approaches as results based accountability (rba) and data driven decision making (dddm). community leaders realized that, if they did not invest in a more sophisticated community data infrastructure, the majority of their day-to-day work would be conducted within a "black box "because they were unable to observe how things were progressing with data. given the shared desire for more intimate knowledge of the local community among both consumers of ci data and cf leaders, the central new york community foundation took several key steps to invest in a better data infrastructure. the cornerstone of this investment was a local survey that it initiated in . the foundation had been frustrated in the past by making investments using publicly available national data only to be thwarted in its efforts to measure and monitor progress using the same data sets (ridzi ) . following investments in new staffing skilled in data analysis and program evaluation, the foundation was able to pilot more rigorous program evaluation of its literacy efforts and furthermore able to document its progress in changing not only the outcomes of program participants, but also neighborhood and community level data improvements (ridzi et al. ; singh et al. ; ridzi et al. ). emboldened by this success the foundation sought to build a similar infrastructure that could be used for other future programming and that could both reliably measure the efficacy of foundation grantmaking and empower local grant recipient partners and collective impact peers to achieve a data driven norm for decision-making, collaboration and ongoing refinement of efforts. in collaboration with nonprofit partners participating in a data learning community the cf built a pilot for real time data sharing across organizations that would allow for coordinated, data driven action yet still protect the client confidentiality of all participating organizations (ridzi ) . in simple terms, this platform consists of a set of commonly used community need and outcome metrics that were utilized across a series of nonprofit partners. the result was a series of new capabilities that strengthened the capacity of both the ci project and the cf. as with other ci projects internationally, the central new york community foundation and vancouver foundation rely on a variety of sources to produce the data they publish related to community well-being. while statistics collected and distributed by national and local governments are cornerstones of the ci for these foundations, both have also found great advantages to commissioning or administering their own surveys of local community members in order to enhance the insights that government-curated data can provide. among the advantages explored in these two comparative case studies are: increased relevance to local concerns, input from community stakeholders, timeliness, granularity to local geographies and the ability to incorporate local perceptions in telling the story of local communities. each of these advantages are deployed to further the field by better measuring well-being and inspiring action but they do so in a way that is consistent with the broader cf field's aspiration of community leadership (cfleads and cfinsights , sacks , ballard , ranghelli . cfleads ( ) has articulated five key elements of effective community leadership: & "engaging residents to hear their concerns, lift up their ambitions and harness their talents. & working across sectors because the challenges facing communities are multifaceted and inter-connected and cannot be solved by any one entity or sector. & commissioning and disseminating local data and research to help understand the nuances of community challenges and provide information to help solve problems. & shaping public policy, recognizing that government systems have a significant impact on the lives of every resident. & marshalling resources beyond the foundation's own grantsfrom private foundations as well as from local, state and federal governmentto address community needs (p. )." as seen in table below, both of the cfs profiled have used local surveys to enhance their community leadership capacity in different areas. in the following sections we explore each initiative's efforts in greater detail so as to demonstrate the multiple ways in which surveys can be deployed to address different leadership goals. both cfs and ci exist in large part to serve the needs of a community's residents. this, however, has not always meant that residents have had a clear voice in the work of these institutions. conducting a community survey can be one strategy for involving those who live within a community and incorporating their perspectives, concerns and ideas. in the case of vancouver foundation, engaging residents can be clearly seen in both the survey and community conversations which take place as a result of (or a precursor to) the report. in , when the report was released, nine british columbia cfs used the survey data and another stated they planned use it the following year either through a report, community conversations or to inform their work. intentionally seeking to harness the talents of local residents, vancouver foundation's open license policy provides opportunities for others to develop ideas, content, products, and services in ways that benefit the community and unlock the full value of resources such as vital signs. the contents of vancouver foundation's vital signs report were made available under this license, which applies to all of the data and means it can be used for other work, as long as vancouver foundation is credited as the source of the content. to further reinforce that survey data collected by vancouver foundation is intended as a community resource, the vital signs website was created in a way that allowed data to be easily downloaded and shared in a usable jpeg format. the vital signs survey results have helped vancouver foundation better understand the communities it serves, and in some cases has surfaced new priority areas. a suite of survey questions in helped to identify belonging as a focus which led to the expansion of a neighborhood grassroots granting program. vancouver foundation's vital signs projects are part of an ongoing commitment to understanding the priorities and experiences of community. it is used to inform and guide work as a funder, partner, and convener, and share it with organizations with the hope that it might create new opportunities from the data and findings. in terms of increased input from community stakeholders, warner ( ) has argued that, "many early community indicator projects were driven by a desire to democratize datato make information more available to the general public ( )." such democratization is two sided in that it can mean both greater access to data and greater input to the focus and design of data collection. for vancouver foundation, the creation of the first provincial survey in involved extensive input from community stakeholders. there was recognition that based on geography, economic conditions, and urban or rural setting, communities experienced different challenges and opportunities and had different needs in terms of usable data. a draft of the survey was created with input from an advisory committee of community stakeholders and was then shared with all british columbia cfs for their suggestions and revisions. not only did this approach result in a survey more reflective of the province, it served to increase use of the findings. in , when vancouver foundation sought to create a new provincial survey with a target focus on community participation, a decision was made to seek input earlier in the process. a half-day session was held with participants comprised of individuals the foundation had worked with before, as well as those who have never previously engaged with vancouver foundation. from the workshop, four main areas were identified to focus on for the survey questions, along with assistance from the mustel research group, questions were then crafted around the focus areas. they were then tested and revised with feedback and suggestions from staff, british columbia cfs and a research advisory committee. for the central new york community foundation, resident engagement is more of an aspirational goal based on the approach of human centered design (hsd). hsd is an approach to problem solving that keeps the human element of needs and assets at the core of the process and continues to circle back to people to be accountable to solving their problems (harte et al. ; bannon ) . because the survey collection data platform relies on collecting data directly from the clients of each participating nonprofit, rather than relying on the perspectives of nonprofit staff as had been prevalent in earlier times, the data are based on the real-time experiences of residents. as a result, when it comes time to plan policy or program related responses, participating organizations are equipped with the ability to rapidly identify which of their clients are experiencing specific needs and reach out to these clients to invite them to focus groups or other ways of sharing their personal insights. the result is a framework and infrastructure that facilitates human centered design -an emerging best practice that involves clients in the initial design of programmatic responses to their needs but then continues to engage them as future iterations and refinements to those programming responses are developed. such programming efforts have historically taken shape within specific sectors and are siloed or disconnected from other sectors. for the central new york community foundation, avoiding such disconnects has been an ambition from the launch of the local survey. the idea of working across sectors has been at the heart of the national rise in popularity of collective impact and community coalition work (ridzi and doughty ) . inherent in this popularity is the recognition that communities face challenges that are not easy to solve. oftentimes referred to as "wicked" social problems, they are multifaceted and interconnected such that individual sectors (such as schools, healthcare, government etc.) are unable to solve them on their own. this recognition was at the heart of the central new york community foundation's local survey design and launch. in this case, it was a group of community stakeholders who first formulated and piloted the local survey (in collaboration with the central new york community foundation). a member of the adult education roundtable of the literacy coalition of onondaga county shared an intake survey that they used with their clients with the group and this was later refashioned into the survey that was administered across all of the participating members in that roundtable group. this input allowed for a survey that was responsive to the needs of this group and inclusive of their primary concerns such as learning disabilities, educational attainment, and access to educational resources. however, it was also designed to be cross-sector and this has led to its uses as a match making tool across sectors. eventually the survey was adapted across nonprofits from a wide range of sectors ranging from hospitals to early childhood service providers, community centers and antipoverty programs. because organizations were now sharing data in real time, while still protecting confidentiality, a new form of data-facilitated collaboration was possible. the central new york community foundation allowed this network of cross-sector organizations to intentionally seek out opportunities to work across sectors through what came to be referred to as "data dating" (ridzi ). this was a way for organizations to be much more specific in how they reached out to organizational partners. rather than reaching out based on preconceived notions, organizations could now use data to identify other organizations that either had a shared need so that they could apply for grant funding together or a need that was complementary to an existing asset. for instance, an organization focused on job training could browse the needs of other organizations providing services such as food pantries etc. to find where there were many potential recruits for their programming. this would lead them to reach out to the organizations that were already serving those clients and test the waters for potential collaboration such as opening satellite sites, formalizing client referrals and other ways of rethinking how their different organizations and missions could complement one another. having a local survey has helped the central new york community foundation to tell the stories of its communities not just from their perspectives, but also the perspectives of charities that were increasing their sophistication in the areas of working across sectors. as one shared, "sometimes in syracuse, organizations tend to work in silos and there are not always a lot of opportunities to meet and exchange ideas," one nonprofit survey participant said. "this provides us with an opportunity to all get to the table and examine through data how we can work through problems collectively." because the data collected by each organization were geocoded to census tracts before being anonymized and shared across organizations, the data could then be analyzed according to very granular neighborhood geographies. this allowed for an approach known as "hotspotting" in which key neighborhoods that were experiencing increases in particular needs could be identified and resources could be pulled together across organizations that were serving clients in the same neighborhood that experienced the acute needs. for instance, one neighborhood community center was able to use the data to plan a community day, to bring in agencies that provide services toward the greatest needs reported in their clients' assessments. as they shared, "when we evaluated the data that we and our… partners gathered, it became clear to us that we needed to double down on our food pantries," and "we found that there is a real need for food and personal items within some neighborhoods of the city, and we need to increase our efforts to get funding that will allow us to increase our supplies." as the saying goes, all politics are local. the same can be said about community needs. knowing about current needs is only part of the battle. knowing where they are concentrated is another key point of data. in the words of the nonprofit that planned the community day, "this tool gives us opportunities, especially with live mapping, to identify locations where interventions can be made… such an opportunity to identify unanticipated needs was so powerful and some partners were so surprised by what they found that they ended up using the data for strategic planning". it is not uncommon for people seeking ci data to presume that certain data sets exist and are accessible only to be surprised when they are unable to find such data. publicly available government data only go so far and, as a result, communities trying to address needs that arise from resident concerns find that they are not always able to rely on data to understand the nuances of their community. the provincial survey, managed and funded by vancouver foundation, enabled cfs to use the survey data specific to their region to supplement the work they were already doing and pair it with local secondary data. for some of the smaller foundations, the survey research made it possible for them to take part in the initiative they otherwise would not have been able to. for instance, the sunshine coast community foundation, who had not intended to produce a report in , received such a great response rate from their community, that they decided to publish a four page mini report with key findings from the region. community foundation driven survey findings can serve as a source of free, unbiased research for citizens, local government, businesses and service providers to better understand their community and take action. it is a resource to help mobilize community knowledge and identify community priorities. the survey component of the vancouver foundation work has evolved since the first report in . for the first survey, ipsos reid research firm was commissioned to conduct an omnibus survey with four quality of life questions. in total, a random sample of vancouver residents was polled through a telephone survey. this was combined with an online perceptions survey where close to informed citizens, comprised of civic, nonprofit and business leaders, were asked to assign a letter grade and identify top priorities for the issue areas. although the response rate increased in and , when the report changed its reach to the larger metro vancouver area, the approach remained the same with a random quality of life phone survey and a targeted online survey for citizen graders. in the approach was simplified to have one comprehensive survey, conducted online, which included quality of life questions, grading for the issue areas and identification of top ways to improve the issue areas. the survey was distributed through environics research to their panels and received almost responses. in , the foundation had a desire to expand beyond metro vancouver to a provincial survey. the reason for this was to provide a resource for the other cfs around bc to help with their vital signs projects. although cfc provides access to existing supporting data, primary research is time consuming and expensive to collect, so by acting as a data collection point for the province, the information could be shared widely to provincial cfs to reduce costs and avoid duplication of effort. by taking this approach, vancouver foundation would be able to provide communities around the province with data tables for their area which could then be incorporated into, or used to supplement, vital signs projects. a second rationale was that, as a provincial funder, it was a way to better understand the communities served and to learn about regional differences, similarities, issues, and opportunities. the creation of a provincial survey allowed vancouver foundation to provide regional and local data to all cfs in british columbia. this was an important shift as it enabled cfs at a local level to use primary research in their own vital signs projects to tell the story of their community, which could then be paired with national data provided by cfc, or local sources such as libraries, municipalities or post-secondary institutions. any community with a minimum response rate of received the data tables for their area. in total, communities achieved this number. sixteen regional reports were also created, based geographically off the health regions in the province. the expectation that each community collect a minimum of surveys highlights a principle of "sweat equity" such that participants feel that knowledge and resource sharing are not one-sided. in the case of the central new york community foundation, participating organizations were also required to collect surveys before they were granted access to the data collected by other participating organizations. in both cases this expectation of sweat equity helped to fuel a larger network of data sharing that has the potential to inform communities about localized needs as they fit into a larger community context. this expectation of sweat equity as a form of positive peer pressure to collect data for the common good also highlights the lack of available data for the community and the niche that cfs can play by commissioning, championing and spearheading local data collection. timeliness is a key part of the value added of commissioning data collection. vancouver foundation launches its survey in late spring/early summer for the years it produces a vital signs report. the report is released the first week in october and community conversations often take place within six months of the release of the data. this increases the confidence of those consuming and using that data on current perceptions and actions of residents. a key way that cfs can fulfill their leadership role is through convening and facilitating knowledge sharing. however, with limited time and resources, this can present a challenge for many looking to engage in this work. vancouver foundation was able to support capacity in this area by customizing tool kits of resources and data for use by the cfs in british columbia. a starting place for this work was hosting webinars and creating a document to help the foundations understand how to interpret the survey data, and further how it could be used. to assist further, community conversations toolkits were created. these were intended to allow cfs to use their local knowledge and connections to focus on the issues of most importance to them, while minimizing the time and effort required to host the events. the kits included: posters and social media promotional templates; customized data sheets for the area; conversation worksheets which included local data specific to the topics selected by the community, signage, copies of the report, and an event guide book. foundations were also given a small grant to help with the costs of rental space, catering and audiovisual equipment. squamish community foundation was one of the foundations that utilized the toolkit to host a community conversation. the conversation was held in the spring with the goals for the event including a discussion on areas of concern, evoking positive change, and enriching the quality of life for squamish residents (green ) . information from the event was then used to help inform direction for their vital signs report which was set to release in october . the capacity crowd at the event included the mayor and local experts who moderated the table discussions on key concerns such as housing and youth engagement. basing the conversations around the survey findings for the area was highly valuable for the community as it enabled a data-centered discussion rather than speculation on top resident concerns. in the case of the central new york community foundation, data sharing is done more on the network level (i.e. organizations that participate in the survey are able to see each other's data but those outside of this group do not have access). for these groups, timeliness and specificity to their clients' needs are paramount. previous experiences with long delayed data have haunted the central new york community and made it challenging to feel as though community efforts were responding to the here and now, rather than to last year's problems that we were just hearing about now. the difference was quite noticeable once the survey was launched. several nonprofits, as well as the central new york community foundation, noted increasing need in such things as food insecurity in real time and had conversations about these internally before talking about potentially collaborating to take action. by the time such groups connected they were already thinking about what other organizations to reach out to for collaboration. community foundation and ci initiatives are both often quite aware that they cannot solve the social problems they focus on by themselves. in the case of ci projects, there is a realization that the major goal is to identify and bring awareness to community needs, and then to hand off the work of addressing those needs to other community actors. for cfs, the role may include identifying funding needs and raising awareness but then extend into funding pilot projects and collaborations or collective impact coalitions to work on addressing those needs. however, even in these cases there is an awareness that foundation resources are limited and insufficient to address wicked social problems without the involvement of government. governments have access to a variety of data sources that ci projects and cfs do not. however, the form and format of these data are typically mandated by federal and state/ provincial source so governments, even local governments, seldom have time to explore the nuances of local needs through conducting local surveys. in the case of the central new york community foundation, the local survey helped to bolster efforts to shape public policy pertaining to lead poisoning. the central new york community foundation run ci project (cny vitals) revealed that lead exposure among children was three times higher in the county as compared to neighboring counties. however, these publicly available data were several years delayed in being released and they were not nuanced enough to understand the dynamics behind this problem. after reviewing more recent administrative data on lead exposure, the local survey being administered was able to probe deeper by asking about whether people had their homes or children tested for the presence of lead. noting a high proportion of families indicating that they were not being tested and noting this was increasing in real time provided confidence that this was a problem that was far from solved. furthermore, it was of a magnitude that could not be addressed with limited cf funding. as a result, the foundation took a role in actively supporting policy change in the form of a city ordinance to make testing for the presence of lead a requirement for rental apartments. this would solve the problem of people not having their homes tested. with the passing of this ordinance on july , this change in government systems promises to have an impact on the lives of residents that will extend far beyond the limited resources at the disposal of the foundation. in addition to directly advocating for government policy change, ci and cfs can leverage local surveys to address the systems by which governments get their work done. government systems involve both formal government and the many nonprofits they contract with to carry out direct service delivery. in the case of the central new york community foundation's work in syracuse, a close dialogue with the city about lead exposure and what to do once lead was discovered revealed that there was a dearth of local contractors that were trained in safe renovation practices in buildings that contain lead (potentially resulting in them making the problem worse by spreading contaminants in the midst of renovation). pairing the survey with collaborative relations in this way helped to reinforce that there was a real time need and encouraged collaboration and mutually supportive relationships that offered momentum as the city and county successfully applied for over $ million in federal u.s. department of housing and urban development (hud) funding. the work of foundations in this arena can be less visible and more behind the scenes. this does not mean it is not impactful. this is indeed the case in syracuse since federal officials shared that the foundation's work on bringing attention to this area and committing funding was influential in the federal government's decision to provide funding. the ability to help attract funding brings into focus the critical work of marshaling resources that we discuss in the following section. attracting funding to the community to address community needs is only half the battle. strategizing a plan, orchestrating that plan, and tracking progress involve critical components of follow through and can leverage local surveys. marshalling involves the steps taken to "bring people or things together and organize them so that they can be used in an effective way" including work to "organize information or ideas." in the case of the central new york community foundation, using a local survey has been helpful in marshalling resources around dealing with concentrated poverty by providing insights into community conditions and the success in addressing them. as a community, residents were actively discussing a report that had ranked the community as among the worst in the united states for concentrated poverty. while this alone was sufficient to create robust civic discussion, the community lacked data that allowed for probing the different dimensions of this local concern. poverty is an abstract concept. once addressed in the local survey that was created, however, it was possible to break the experience of poverty down into a variety of categories including housing, transportation, healthcare, clothing etc. being able to focus on this area of local concern also helped the foundation to feel more confident in its grant making and more responsive to the nuances of local need. as sirgy ( ) has asserted, ci projects can take a variety of different value propositions ranging from focusing on sustainability and social cohesion, to social inclusion and empowerment. in this case another of the dimensions he notes, socio-economic security, took first priority. having a local survey also helped the community to take a results based accountability (rba) approach to handling the over $ million in state funding that it successfully attracted to deal with poverty. while the central new york community foundation, and key partners such as the county government, had been interested in pursuing rba, program evaluation level data that could be combined across programs to monitor population level change was difficult to come by. as a result of this new local survey, administered continuously and online, a new source of data emerged that could be aggregated and could then be used to anticipate changes in other more longterm indicators. in one example, programs that received state anti-poverty funding were expected to have their clients complete the local community survey to both notice trends across clients of different organizations (i.e. declining unmet needs is a positive indicator along the pathway out of poverty) and notice opportunities for cross sector collaboration (as described above). in another instance, organizations that received funding were required to keep track of the people they served and to identify them by geographical location (census tract). this resulted in the ability to conduct program evaluation in new and innovative ways that were consistent with rba. for instance, one organization reported significant numbers of clients who were provided transportation services in a select group of census tracts. it was then possible to examine surveys collected in the targeted census tracts and monitor as the reported need for transportation declined. the experiences of the vancouver foundation and the central new york community foundation offer insights for other cfs that are considering investments in local surveys as part of a ci and community leadership strategy. specifically, such surveys offer a tool for conversations and coordination that can help a cf strengthen their portfolio in any of the five key elements of effective community leadership that cfleads ( ) has identified. when it comes to engaging residents, both examples offer helpful insights in their differing approaches. the vancouver foundation targeted the community at large through publically disseminated surveys and this has helped them emerge with a general sense of the opportunities and concerns of citizens across all walks of life. however, this approach is most likely to miss the dispossessed and hardest to reach citizens who most lack a voice. that is precisely the population with which the central new york community foundation sought to connect. in their case, residents had to be a client of organizations that tended to serve those in greatest need in the community. community foundations seeking to engage residents would do well to be clear at the outset about what parts of the population they are seeking to engage. when it comes to working across sectors, surveys can be effective at identifying what sectors should be involved and at gauging the relative magnitude of sentiments and needs. the central new york community foundation began with a mature survey from the human services sector which allowed it to assess the prevalence of multifaceted needs that the human services sector had already established were present (for instance the survey did not just ask about poverty but about the multiple dimensions of poverty). in addition, in order to enable cross-sector collaboration, organizations had to buy in to conducting surveys in which the majority of questions did not pertain to the services they offered (although they were welcome to augment the survey with such questions). only by asking residents about the needs that their services do not provide for could they learn what other sectors they needed to coordinate with. both foundations offer instructive lessons when it comes to commissioning and disseminating local data and research to elucidate the nuances of problems. neither foundation is yet fully leveraging local surveys to the full capacity of addressing all five community leadership components. this is partly a function of time; these communities may eventually evolve to utilizing local surveys to bolster their portfolios in all five elements. it is also a function of the fact the local surveys incur costs that must be balanced with the realities of finite resources. these include not only the costs of doing the survey work itself, but the time and resources needed to deal with the complexity of coordination with partner stakeholders. in recognition of the high cost of conducting surveys, the vancouver foundation views funding a provincial survey as one of the ways it can support and help build the capacity of other cfs in the province to take on their own data based projects. while the central new york community foundation supports nonprofits in administering their own surveys, this is not without its own cost to staff time. however, because it aligns with strategic plan goals (i.e. capacity building efforts among nonprofits), much of this work is done in a collaborative learning community setting with nonprofits focused on improving performance management skills, which helps to justify the use of staff time. when it comes to the complexity of coordination with partner stakeholders, vancouver foundation has found that those aged - can be a challenging group to reach for survey participation. in order to achieve a representative sample for vancouver foundation's provincial survey, social media boosts were purchased for facebook and instagram, extra outreach efforts were conducted with youth serving organizations to distribute the survey and an additional youth panel was accessed through mustel research group. province-wide representation would not have been possible strictly through typical research panels which tend to have representation from the larger centers. outreach by cfs in the province helped to address this issue. taken together, this enterprise, like many community initiatives, moves at the speed of trust. for both communities, the survey efforts started small and began to grow in the fashion of a snowball as they gained momentum over time. in the area of shaping public policy, local surveys can be very helpful as the source material for public policy advocacy, white papers and complex policy discussions. the added specificity and real-time nature can also provide assurances that the foundation is directing its advocacy at the optimal policy levers that will address community needs or build on strengths and talents. finally, surveys can help with marshalling resources because they offer a specificity about community issues that is not often available in publically collected data. just as importantly, they offer moveable numerical targets (such as the percent of respondents that report a specific need such as transportation) that donors and other partners can all unite their resources around. focus on the creation and use of local surveys highlights some of the key synergies between the ci and cf movements. it also helps to add new perspective to the already interdisciplinary study of community well-being. the cf and ci movements intersect and find synergies in their shared love of place and passion for location. but beyond their shared interest in the local communities where they are anchored, they both seek community engagement through conversations and better coordination among local stakeholders. it is in service to this ideal that we see such strategies as resident engagement, commissioning data collection, data dating and co-creation of shared metrics to facilitate collective impact and results-based accountability. coordinated ci projects and cfs serve to raise each other's profiles and mutually reinforce each other's missions. furthermore, they have a symbiotic relationship in that ci's address the cf need for community knowledge to invest in projects focused on well-being while cf's offer a steady source of funding for cis. both ci projects and cfs see mission overlaps when it comes to striving for expertise in the areas of: -knowing the community, -long-term focus and -results driven learning organizations that seek to evaluate impact. as mazany and perry ( ) point out, cfs are increasingly carving out their market niche in relation to their specialized local knowledge and personalized service. when comparing them to other philanthropic mechanisms, the distinguishing factor of cfs is in knowing the community (cfleads ). community foundations tend to be results-driven learning organizations that seek to engage in and evaluate the impact of their community leadership work (cf leads : ). in this article we have explored this within the framework that cfleads ( ) has articulated around the five key elements of effective community leadership. we have focused on how the two cfs studied have leveraged a local survey component to their ci work in order to improve their competency for these elements. specifically, we explored how a local survey can foster better engagement with residents around their concerns and the ways their ambitions and talents can point us toward solutions. we have seen how surveys can enable the service delivery community to work across sectors and we have seen how surveys can position foundations to originate and disseminate local data that can provide insights into the nuances of community challenges. all of this work empowers cfs to have a confident voice and to speak up in the service of shaping public policy; and more strategically to help in marshaling local resources. as slutsky and hurwitz ( ) assert, "community foundations raise the patient capital that allows them to stick with issues, even difficult ones, over the long haul. entrenched poverty and environmental degradation will not be solved during our lifetimes. fixing the schools, creating jobs for all who need them, and reforming healthcare will take years of hard work and perseveranceand reliable, patient capital. it's no accident that philanthropy often focuses on "intractable" problems (p. )." by focusing on identifying and then deepening understanding of such social problems through local surveys, cfs and ci strategically invest in detailed knowledge that can empower the communities they serve to take data driven action. they further reinforce the nexus of their missions by strengthening the leadership roles they play in monitoring and improving community well-being. data availability not applicable. conflict of interest 'not applicable'. code availability 'not applicable'. community foundations and community leadership a human-centred perspective on interaction design created by the national task force on community leadership prepared by cfleads and aspen institute community strategies group elements of effective community leadership assessing community foundation needs and envisioning the future dimensions of the field: an in-depth analysis of the community foundation movement connecting the dots with conversation: squamish will discuss areas of passion and concern community foundations: agility in the duality of foundation and community. the routledge companion to philanthropy a human-centered design methodology to enhance the usability, human factors, and user experience of connected health systems: a three-phase methodology embedded philanthropy and the pursuit of civic engagement modeling community well-being: a multi-dimensional approach economy doesn't buy community wellbeing: a study of factors shaping community wellbeing in south korea merging money and mission: becoming our community's development office here for good community foundations and the challenges of the st century here for good community foundations and the challenges of the st century vital signs: connecting community needs to community philanthropy in canada. the philanthropist the role of community foundations in the big society: taken for granted ensuring there is "community" in the community foundation here for good community foundations and the challenges of the st century knowledge as leadership, belonging as community: how canadian community foundations are using vital signs for social change vital signs: an exploratory case study of community foundations' local collaboration in a national program context measuring community foundations' impact. nonprofit sector research fund working paper series managing expectations when measuring philanthropic impact: a framework based on experience community indicators and the collective goods criterion for impact collective action, collective impact and community foundations: the emerging role of local institution building in an era of globalization and declining social safety nets goldilocks data-connecting community indicators to program evaluation and everything in between does collective impact work? what literacy coalitions tell us the imagination library program: increasing parental reading through book distribution the imagination library program and kindergarten readiness: evaluating the impact of monthly book distribution community quality-of-life indicators: best cases viii community foundations: symposium on a global movement-current issues for the global community foundation movement informed by knowledge shared and lessons learned. worldwide initiatives for grantmaker support (wings) the growing importance of community foundations. indianapolis: indiana university lilly family school of philanthropy retrieved on exploring the literacy practices of refugee families enrolled in a book distribution program and an intergenerational family literacy program what types of indicators should be used to capture community well-being comprehensively? int here for good community foundations and the challenges of the st century indicators and community well-being: exploring a relational framework evening standard dispossessed fund building philanthropic and social capital: the work of community foundations in federal reserve bank of san francisco & the urban institute (authors) publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations he is a past president of the literacy funders network, an affinity group of the council on foundations. frank holds a masters degree in public administration and a ph.d. in sociology from syracuse university's maxwell school. he also carries a certificate of advanced study in women's studies. prior to joining the community foundation vital signs reports, as well as the connect & engage report. prior to joining vancouver foundation, trina worked for years at bc children's hospital as an educator for the injury prevention program before transitioning into fundraising at the foundation. she is currently the director of partnerships and engagement at minerva bc. she holds a master of philanthropy and nonprofit leadership from carleton university in ottawa, canada, as well as a graduate diploma in social innovation from the university of waterloo and a ba in communication from simon fraser university key: cord- -axbyav m authors: kimball, ann marie title: emergence of novel human infections: new insights and new challenges date: - - journal: international encyclopedia of public health doi: . /b - - - - . - sha: doc_id: cord_uid: axbyav m novel human infections have continued to emerge over the past decade. their presentation, epidemiology, and microbiology have shifted the paradigms of traditional science. in particular insights into nongenetic or paragenetic mechanisms (plasmid mediated), modes of infection have challenged biology. in reviewing the new challenges posed by these emergent events, new technologies promise some answers; however, global health security against pandemic threats, particularly given the uneven distribution of global resources for prevention, detection, and response, remains a critical area of challenge. new human infections have continued to come forth over the last decade. this discussion will focus on the period from to . given the importance of the severe acute respiratory syndrome (sars) as the harbinger of coronaviruses such as the middle east respiratory syndrome (mers), some discussion of sars is also included. the phenomenon of emerging infections has been constant with the majority of human infections reflecting the introduction into humans of zoonotic pathogens. over the last decade, great progress has been made in defining more fully how emergence occurs. in fact the emergence of new infections has expanded the paradigms of microbiology in a number of ways, which will be highlighted here. specifically: ( ) it is now well appreciated that influenza can migrate directly from avian sources to humans, and the appreciation of the actual directness of 'species jumping' has moved forward; ( ) new infections have also introduced uncertainty in transmission dynamics with emphasis on super-spreader events as well as nosocomial transmission; ( ) infectious particles are not confined to those organisms which contain genetic material; ( ) a new paradigm such as 'planetary health' may be necessary for defining these trends; and ( ) global preparedness and response is not in place for the next pandemic. for further background information, the reader is referred to the original article on this phenomenon (kimball, ) . a general discussion of antimicrobial resistance and xenotransplantation is not included in this discussion as they were thoroughly covered in the original article. antimicrobial resistance will be covered in detail in another article of this volume. nonetheless they continue to be important considerations. while it has long been appreciated that the majority of human pathogens arise from zoonotic sources, the directness of the path from animal to human has become clear. ideally detecting pathogens in animals could be seen as a harbinger for human outbreaks. in fact this has been a working hypothesis of major us agency for international development (usaid) funding to their pandemic agents program. however, recent outbreaks of influenza, sars, and mers coronavirus (cov) demonstrate how emerging infections are shifting this longstanding paradigm. they lend further urgency to this area of research. in addition, these outbreaks have challenged our understanding of transmission dynamics. empirical observation has shown that there is not a single transmission force 'number' which completely characterized the spread of infectious diseases. this further complicates efforts to control infection within populations. in , a cluster of high mortality influenza cases was detected in mexico. an observational study of patients hospitalized in mexico between late march and june showed that pandemic (h n ) disproportionately affected young people. fifty-eight patients ( . % of those hospitalized) became critically ill, with complications including severe acute respiratory distress syndrome and shock. among those who became critically ill, the mortality rate was % (domínguez-cherit et al., ) . the pandemic and its management have been the subject of an in-depth analysis commissioned by the world health organization (who), and that analysis proved prescient in more recent global outbreak events such as ebola (who, ) . this cluster heralded a global pandemic and the declaration by who of a public health emergency of international concern (phiec). it occurred in the context of a decade of planning for a potential h n outbreak, which included who updating its pandemic guidance (pandemic influenza preparedness and response, ). in a small but lethal cluster of influenza occurred in children in a hong kong nursery. of the cases, died (mounts et al., ) . science shifted its understanding of influenza and recognized that flu could come directly from birds to humans. in fact h n , which emerged in , acquired the popular moniker of 'bird flu.' the outbreak was curtailed through active surveillance, changes in practice, and poultry culling of live markets in hong kong. however, the outbreak proved a harbinger of more widespread recognition of 'bird flu.' h n was identified through active surveillance of poultry and wild birds; waterfowl were particularly affected. human cases were sporadic but carried a very high mortality rate (estimated at %) (webster et al., ) . although the virus proved difficult to transmit to humans, case fatality was high. as of february , about laboratory-confirmed human cases had been reported to the who from countries; about % of reported cases were fatal. the spread of h n was geographically broad with extension into nigeria and throughout southern and se asia in waterfowl and in domestic fowl. extensive planning for a potential pandemic was put into place given the apparent proximity of the threat and the high mortality in humans. veterinary and human health collaboration was a central precept of this planning in the 'one health' concept (heymann and dixon, ) . the h n threat did not materialize despite the high level of circulation in birds. preparedness in se asia in particular included tabletop exercises, culling of birds through rapid response, and at least one joint investigation carried out between laos and thailand. in this setting, h n ran its course, with a milder clinical syndrome (although it is estimated that the global death toll was ). the pandemic of h n precipitated some confusion as well as competition for access to antivirals and vaccines. in the aftermath of these contentious discussions, new policy initiatives were put into place. this included the 'pandemic influenza preparedness' (pip) (who) plan which took some years to negotiate. it balances access to new viral strains for vaccine production with access to these vaccines for poor countries. the fineberg commission to examine an 'after action' performance of the international health regulations (ihr) was central to potential reform as well. this will be more fully discussed below. in a new influenza virus, h n , was isolated from patients in the people's republic of china. isolates were both from birds and from humans. although cases occurred globally with deaths, international spread was limited to two countries. the national response to this epidemic was very strong which is a key to control (discussed below). the influenza pandemic also followed another global respiratory emergency, sars. the etiology of sars (a new coronavirus) was not known in late when cases and deaths began to occur in guangdong province of the people's republic of china. initially misdesignated as a chlamydial pneumonia early in the course, public alarm mounted as antibiotics proved futile in treatment. between november and july , a total of probable sars cases were reported from countries with deaths for a mortality rate of . % (mmwr, ) . sars effectively demonstrated the potential mobility of respiratory pathogens. while sars was declared poorly transmissible, it effectively jumped continents in travelers and infiltrated populations through nosocomial spread. in contrast to influenza, which is highly transmissible, sars still requires direct exposure to bodily fluids for transmission. however, sars shifted the scientific paradigm of zoonotic transmission more fullywith incrimination of wet markets vending civet cats initially thought to be the source. this initial assessment has proved less robust in terms of 'reservoir' for new human pathogens as discussed below. sars also challenged our understanding of transmission dynamics. for reasons that remain unclear, a single infected person who spent a single night in a hotel in kowloon resulted in geographically broad transmission. the concept of a 'superspreader' was popularized (lloyd-smith et al., ) . this phenomenon was also described in a second scenario in beijing (shen et al., ) . traditionally infection has been characterized by a 'reproductive rate' which is essentially the rate at which an infectious case replaces itself. if the rate is , then there will be no spread, as the infection will simply stay the same absolute number as the index case recovers. however, if the rate is higher (i.e., > ), then spread into the population will occur as a single case infects multiple individuals so the number of cases increases. super-spreaders seem to have high infection rates although the overall rate for the pathogen in question may be low. this has, of course, changed our assumptions for modeling disease spread in populations. following the h n pandemic (and the avian influenza emergence of ) and the sars pandemic of , a new virus emerged on the arabian peninsula. mers-cov is a new human pathogen that also causes pneumonia and respiratory distress. the story of mers is less history and more present in terms of defining its epidemic potential. it reinforces the need for 'one health' collaboration between veterinarians, clinicians, and public health specialists, making use of their relative expertise. mers was first reported in as a case report of a patient in an icu with severe respiratory disease from jordan (hijawi et al., ) . at the time of this writing, cases and deaths have been reported to the who, with an average case fatality ratio of %. in one epidemiological analysis, the case fatality ratio for primary cases was % ( % ci, - ), whereas for secondary cases, it was % ( % ci, - ) (alsolamy, ) . like its coronavirus cousin, sars, mers-cov has demonstrated agile spread within hospitals (oboho et al., ) and across continents. in a large outbreak occurred in south korea (cowling et al., ) . that outbreak was characterized by a mortality rate of about % among cases, were fatal. it also featured 'superspreading' events. in fact a single case housed in the emergency room with persistent cough was linked to cases in one hospital (kucharski, ) . to summarize, the recent episodes of respiratory infectious diseases related to influenza, sars-cov, and mers-cov have demonstrated increasingly direct links between animal and human infections, agile intercontinental geographic spread, and complex transmission dynamics including 'superspreader' events. transmission within health-care settings has also been a prominent feature. these characteristics have challenged traditional assumptions about the pathogenesis and epidemiology of infectious diseases. traditionally microbiology has held that microbes (bacteria, viruses, protozoa, fungi, etc.) are organisms that replicate through genetic mechanisms. that replication is a major factor in the illness in humans these agents cause. recent emerging infectious events have brought an additional complexity into that decades' old assumption. a new form of a human neurodegenerative disease that emerged in britain in the s was linked to the emergence of bovine spongiform encephalitis (bse) in cattle ('mad cow disease'). this link was demonstrated through multiple casecontrol studies. the biological proof of a common etiology came somewhat later (hill et al., ) . prions are not microbial life in the traditional sense. they are 'autocatalytic proteins' or proteins that make change. in the instance of 'transmissible spongiform encephalopathies' (tses) of mad cow disease (bse), sheep 'scrapie,' elk chronic wasting disease, as well as in the human diseases of creutzfeldt-jakob disease (cjd), new variant creutzfeldt-jakob disease (vcjd) and kuru, these changes occur in the central nervous system. while the new vcjd epidemic related to ingestion of infected beef from bse-affected cows has waned due to enhanced global surveillance and animal husbandry practices, research into prion disease continues. it appears that despite their lack of genetic material, prions do undergo mutation and strain diversification in response to selective pressures (collinge et al., ) . soberingly, it is believed that some humans (estimated in britons) silently carry pathogenic prions for many years. this risk persists and creates safety concerns for blood transfusions and organ transplantation. the story of bse demonstrated the limitation of the traditional assumption that genetic reproduction of pathogens is necessary for infection as outlined above. the uk beef industry had historically been a relatively stable one when fragmented among many smaller farms across the british isles. to protect this industry, the government maintained a tariff on the imports of competing products from abroad. with the explosion of global trading in beef after world war ii, coincident with refrigerated transport, and the movement toward global free trade, the united kingdom negotiated a timetable under the general agreement on tariffs and trade to scale down tariffs on beef, which heightened competition in the uk beef industry and increased pressure for more efficient and less costly production methods. against this backdrop, innovation in rendering was introduced into the slaughterhouses of the united kingdom. the rendering or processing of carcasses of cows and other animals after the edible and usable bits of flesh and meat have been cut away has been done for centuries. and for decades, uk farmers used the meat and bone meal from rendering as a protein source for beef cattle. historically, the rendering process was similar to pressure cookingapplying very high temperatures for very long times so eventually even the bones broke down into powder. it was an expensive, fuel-consuming, and timeconsuming process. when a new cold vacuum extraction method of rendering was introduced requiring lower temperatures (i.e., less energy) and less time, it seemed a win-win situation considering the increasing pressure on the uk beef industry in the face of global competition. but sometime after the new rendering practice was introduced into the united kingdom, the prion disease known as mad cow disease emerged. the new process, discovered by uk beef industry, was not effectively disinfecting for prions. existence of prion disease was unknown prior to its dramatic emergence, first in cows and then in people. the context is important to appreciate. somehow the streamlining of the rendering process played a role. british scientists tested the new process by deliberately introducing animals with mad cow disease and assaying the resulting meat and bone meal product. they found that the newer rendering process does not remove the infection, whereas the older process did. zika virus emerged in sub-saharan africa in the late s. it is a close cousin of dengue virus and in the same family as yellow fever. all of these viruses are transmitted to humans through the bite of a mosquito. all of these diseases are clinically mild, but occasionally severe causing fever, rash, and joint pain. unfortunately all of these diseases have become globally distributed. zika is the most recent arrival in the americas. it has circulated in asia for some time (chen and hamer, ) . while clinically relatively mild, epidemiologic studies in brazil have suggested a link between zika virus and severe birth defects in newborns. viral infection in early pregnancy appears to be associated with microcephaly, which is associated with profound brain injury in newborns. again, the emergence of a new infectious disease is pushing the boundaries of biomedical knowledge. in the absence of certain prevention or treatment options, the government of brazil has gone as far as advising women not to become pregnant (mcneil, ) . the emergence of antimicrobial resistance has continued to be a major concern. in a new enzyme in gram-negative bacteria was detected which caused broad antibiotic resistance. this enzyme was produced by mobile genes that travel on plasmids. plasmids are small circular dna (genetic) packages, which are distinct from the dna of the bacteria itself. these are mobile, with the ability to be taken in across classes of bacteria if and when they confer a selective advantage for survival, as in the case of antimicrobial resistance. the new enzyme ndm- (new delhi metalloproteinase- ) was traced to an infection that occurred in patients who had been treated in india. a more complete study of the epidemiology of this enzyme in gram-negative bacterial isolates from the subcontinent suggested a broad range of gram-negatives were affected (kumarasamy et al., ) . this new biology, which was first described for extended spectrum beta lactamase (esbl) resistance in the s, has provoked renewed concern in antimicrobial resistance. was declared by the who as the year to address antimicrobial resistance. the pharmaceutical pipeline is bereft of new antibiotics to address this challenge. chillingly another new panresistant plasmid has been reported from china, which is resistant even to the last line of defense, the polymixin class of antimicrobials (liu et al., ) . this report included isolates from pigs at slaughter, retail pig and chicken meat, and humans. again, the specter of intensive agriculture fostering new biological threats calls for careful study. the isolates were largely from areas of intensive porcine agriculture in china. figure indicates sites sampled for polymixin plasmid resistance. the question of where new infections lurk in nature has been an active area of research. as noted above, the initial reservoir for sars coronavirus was thought to be civet cats which are domestically raised for food in china. however, further investigation has suggested that there may be a single host involved in many emergent diseases. in an elegant demonstration of interdisciplinary research, han et al. ( ) have recently published a persuasive article on the role of bats in emerging infections. whether or not the theses of the article prove true with further research, the work provides additional evidence of how extremely powerful interdisciplinary research can be toward solving the puzzles of emergent diseases in humans. in discussing the spillover of viruses from bats to humans, the authors write: factors that contribute to the intrusion of bats into human living environment can be summarized into a 'push' and a 'pull' (brüssow, ) . a 'push' refers to the enormous demand for more space and resources brought by the human population explosion, which leads to the destruction of bat habitats and shortage of food. natural environmental changes, such as typhoons and droughts, can also place stresses on bats. a 'pull' involves the living environments built by humans, characterized by urbanization, intensive agriculture and food animal breeding, which attracts bats into human living environments for an abundant of food supply. so coming full circle, this discussion highlights the critical importance of further understanding these events of 'species jumping' or 'spillovers,' given the pressures will only augment rather than abate. infections potentially housed in bats as their natural reservoir (from han and colleagues) is shown in table . it is an impressive array, which brings us to consider how indispensible further understanding in these interactions is to gain insight into emergent human infections. so what explains the apparent increased pace of emergence of new human infections? is it simply that we are more able, with our new technologies, to detect them? or are there forces at work that are fostering this trend? the stories of bse and nvcjd recounted above were outlined because the united kingdom, although a small country, has excellent epidemiologic, statistical, laboratory, and clinical acumen. while cases of bse and nvcjd were not confined to the united kingdom, the origin of emergence was tracked and described relatively efficiently. but, what of influenza? the potential contribution of intensive poultry and swine agriculture to the emergence of influenza a emergence was outlined in my earlier article for this publication. research over the past decade has continued to provide evidence of this risk. as intensive practices have spread to developing countries, the assurance of biosecurity has become less sure as noted in the discussion (above) of polymixin resistance through plasmids in pigs and humans. while many new strains of influenza arise in wild birds (particularly waterfowl), the link to human populations appears to be through domestic poultry (leibler et al., ) . however, other anthropogenic mechanisms are also at play. without the global 'mobile' environment of travel and trade, emergence would remain a largely local phenomenon. however, as we saw with the influenza discussion above that is not the case. nor was it the case with sars or with mers-cov. international tourism surpassed . billion arrivals in according to the world bank (world bank international tourism). after a slump in global trade during the global recession exports of food in reached nearly $ . trillion in value for selected countries where data were available. this, of course, does not include all of global trade, which has surpassed $ trillion in value (merchandise trade by product). guarding against transcontinental transmission in food or through human travel is a complex undertaking, with safeguards at the source the most likely answer. however, research, testing, and demonstration of effective measures remain wanting. finally, climate change, largely attributed to human activity, seems to be readjusting the boundaries of mosquito borne diseases. the recent incursion of zika into brazil is attributed to the el niño weather pattern now in force in that geography. while el niño oscillation is not directly attributable to human activity, the shifting of such natural oscillations and their severity may well be. in his landmark book planetary overload: global environmental change and the health of the human species, anthony j. mcmichael outlines the human-generated stress on natural systems (mcmichael, ) . he posits that food will become increasingly scarce for the human community. the macroecologic effects of human activity on climate, water, food, agriculture, pollution, and human health are well described, but the systematic link between the macrolevel (what we can see) and what is occurring on the microlevel remains an important area of research. to address the emergence of new pathogens, we need more precise knowledge about the mechanisms that form the critical pathway to emergence. a follow-up report to the landmark iom report, emerging infections, microbial threats to health: emergence detection and response was published in (smolinski et al.) (microbial threats to health) . additional factors of emergence were examined in this report: human susceptibility to infection, climate and weather, changing ecosystems, poverty and social inequity, war and famine, the lack of political will, and intent to harm. thus the original factors grew to . while enriching the discussion and description of emergence, this proliferation of factors also created overlapping domains within factors; for example, climate and weather are an integral physical science aspect of ecosystems, the failure of political will is integral to the neglect of public health systems, and so forth. from an analytic point of view, the need for in-depth study of factors and how they actually work has become critical for scientific insight into public health protection. mcmichael has suggested the term 'the anthropogenic epoch' to describe our contemporary situation. in other words, human kind is changing the nature of our environment in unprecedented ways. more recently the rockefeller-lancet commission has suggested the new scientific discipline of 'planetary health' as a unifying concept to bring the disparate strands of life sciences, and ecology more closely together to foster interdisciplinary research and insight (the rockefeller foundation, ). the key to success will require intense investment in transdisciplinary research which brings in disparate databases and talents into risk analysis. while a full discussion is beyond the scope of this discussion, a number of new tools have come into use that allow more rapid diagnosis and response to newly emergent outbreaks. a few will be highlighted here. in addition to formal disease surveillance reporting a number of informal diseases, surveillance networks have arisen among countries which share common borders or work within a common economic bloc. these networks facilitate the flow of information across borders and allow collaborative investigations, tabletop exercises, and resource sharing on an ongoing basis. in postconflict areas such as the mekong basin, they contribute to health security (gresham et al., ) . increasing sophistication of bringing disparate data sets together and creating models to understand possible scenarios has brought additional insight into prevention and control efforts for emerging diseases. prediction of where outbreaks are most likely to occur remains a very imperfect science (jones et al., ) . retrospective niche modeling has brought additional insight into how different factors may interact to foster outbreaks (daszak et al., ) . laboratory diagnosis of unknown agents has also advanced. during the sars outbreak, the who convened an informal network approach to fully sequence the new agent in -month time (david, ) . one group has put forward a vision of bringing full genomic sequencing into the laboratories of developing countries (aarestrup et al., ) . clearly the ability to quickly diagnose new agents without the necessity of culture would be an important advance. as importantly the integration of informatics linking genomic analyses to phylogenetic metadata would allow global tracking of agents. as the boundaries of microbiology are stretched with new insights from emergent diseases, the ability of the people of the world to protect against pandemics is more important than ever. global traffic and trade continue to grow, confounding national approaches with their international span. in (following sars) the who adopted the ihr (international health regulations). this is the only law with the force of an international treaty, which is in place to govern the conduct of countries during global security emergencies. the ihr outline 'core capacities' for national-level protection. it is not the optimal level for an emergent pandemic, but it is the minimum considered essential for global health security. the ihr implementation was to have been completed by all member countries by . however, implementation has languished with only one-third of countries implementing and many not disclosing their status of implementation to the who in . after the influenza pandemic, an independent expert panel was convened to assess how the ihr functioned. that panel, lead by dr harvey fineberg, then president of the institute of medicine, was explicit in outlining the gaps in global health security. the world is ill-prepared to respond to a severe influenza pandemic or to any similarly global, sustained and threatening public-health emergency. beyond implementation of core public-health capacities called for in the ihr, global preparedness can be advanced through research, reliance on a multisectoral approach, strengthened health-care delivery systems, economic development in low and middle-income countries and improved health status. fineberg ( ) . in , ebola (a known infection) emerged in guinea. at the time of its appearance, none of the countries in sub-saharan africa had implemented the core capacities of the ihr (kimball and heymann, ) . the outbreak went on to create pandemonium in the three most affected countries (guinea, liberia, and sierra leone) killing over people (and afflicting more than ) (ebola-situation). infection was introduced in other countries, but onward transmission was limited. following ebola, the international systems are again under review. initial observations remain distressingly similar to those made in . with reform of the un and who, once again underway, it will be important to follow through. of particular importance as highlighted above is the interdisciplinary (and in the case of the un interagency) nature of prevention, detection, and response to emergent threats. despite the new technological tools, the ecological factors in emergence are ever gathering force. clearly additional efforts are required. emerging infections remain an intersectoral challenge with every indication they will continue to be with us over the coming decades. integrating genome-based informatics to modernize global disease monitoring, information sharing, and response middle east respiratory syndrome: knowledge to date zika virus: rapid spread in the western hemisphere preliminary epidemiological assessment of mers-cov outbreak in south korea interdisciplinary approaches to understanding disease emergence: the past, present, and future drivers of nipah virus emergence the international response to the outbreak of sars in critically ill patients with influenza a(h n ) in mexico pandemic preparedness and responsedlessons from the h n influenza of creating a global dialogue on infectious disease surveillance: connecting organizations for regional disease surveillance (cords). emerg bats as reservoirs of severe emerging infectious diseases the value of the one health approach: shifting from emergency response to prevention of zoonotic disease threats at their source epidemiological findings from a retrospective investigation the same prion strain causes vcjd and bse global trends in emerging infectious diseases ebola, international health regulations and global safety factors influencing the emergence of new (and "old") disease, international encyclopedia of pubic health superspreading in mers emergence of a new antibiotic resistance mechanism in india, pakistan and the uk: a molecular, biological and epidemiological study industrial food animal production and global health risks: exploring the ecosystems and economics of avian influenza emergence of plasmid-mediated colistin resistance mechanism mcr- in animals and human beings in china: a microbiological and molecular biological study superspreading and the effect of individual variation on disease emergence planetary overload global environmental change and the health of the human species zika virus, a mosquito-borne infection, may threaten brazil's newborns global health microbial threats to health: emergence, detection, and response by committee on emerging microbial threats to health in the st century update: severe acute respiratory syndrome -worldwide u.s case-control study of risk factors for avian influenza a (h n ) disease, hong kong mers-cov outbreak in jeddah-a link to health care facilities a who guidance document. world health organization the rockefeller foundation-lancet commission on planetary health safeguarding human health in the anthropocene epoch: report of the rockefeller foundation-lancet commission on planetary health h n outbreaks and enzootic influenza report of the review committee on the functioning of the international health regulations the author wishes to thank ms kellie creamer for her assistance in preparing this manuscript.see also: antimicrobial resistance in a one health and one world perspective -mechanisms and solutions; arboviruses; ebola and other viral hemorrhagic fevers; global health law: international law and public health policy; influenza. key: cord- -yac kzaf authors: eden, john-sebastian; rockett, rebecca; carter, ian; rahman, hossinur; de ligt, joep; hadfield, james; storey, matthew; ren, xiaoyun; tulloch, rachel; basile, kerri; wells, jessica; byun, roy; gilroy, nicky; o’sullivan, matthew v; sintchenko, vitali; chen, sharon c; maddocks, susan; sorrell, tania c; holmes, edward c; dwyer, dominic e; kok, jen title: an emergent clade of sars-cov- linked to returned travellers from iran date: - - journal: virus evol doi: . /ve/veaa sha: doc_id: cord_uid: yac kzaf the sars-cov- epidemic has rapidly spread outside china with major outbreaks occurring in italy, south korea, and iran. phylogenetic analyses of whole-genome sequencing data identified a distinct sars-cov- clade linked to travellers returning from iran to australia and new zealand. this study highlights potential viral diversity driving the epidemic in iran, and underscores the power of rapid genome sequencing and public data sharing to improve the detection and management of emerging infectious diseases. from a public health perspective, the real-time whole-genome sequencing (wgs) of emerging viruses enables the informed development and design of molecular diagnostic assays, and tracing patterns of spread across multiple epidemiological scales (i.e. genomic epidemiology). however, wgs capacities and data sharing policies vary in different countries and jurisdictions, leading to potential sampling bias due to delayed or underrepresented sequencing data from some areas with substantial sars-cov- activity. herein, we show that the genomic analyses of sars-cov- strains from australian returned travellers with covid- disease may provide important insights into viral diversity present in regions currently lacking genomic data. in late december , a cluster of cases of pneumonia of unknown aetiology in wuhan city, hubei province, china was reported by health authorities (wuhan municipal health commission ). a novel betacoronavirus, designated sars-cov- , was identified as the causative agent (wu et al. ) of the disease now known as covid- , with substantial humanto-human transmission (lu et al. ) . to contain a growing epidemic, chinese authorities implemented strict quarantine measures in wuhan and surrounding areas in hubei province. significant delays in the global spread of the virus were achieved, but despite these measures, cases were exported to other countries. as of march , these numbered more than countries, on all continents except antarctica; the total number of confirmed infections exceeded , and there were nearly , deaths (dong, du, and gardner ) . although the majority of cases have occurred in china, major outbreaks have also been reported in italy, south korea, and iran (world health organisation a). importantly, there is widespread local transmission in multiple countries outside china following independent importations of infection from visitors and returned travellers. viral extracts were prepared from respiratory tract samples where sars-cov- was detected by reverse-transcription polymerase chain reaction (rt-pcr) using world health organisation ( b) recommended primers and probes targeting the e and rdrp genes. in new south wales (nsw), australia, wgs for sars-cov- was developed based on an existing amplicon-based illumina sequencing approach (di giallonardo et al. ). viral extracts were reverse transcribed with ssiv vilo cdna master mix and then used as input for multiple overlapping pcr reactions ( . kb each) spanning the viral genome using platinum superfi master mix (primers provided in supplementary table s ). amplicons were pooled equally, purified, and quantified. nextera xt libraries were prepared and sequencing was performed with multiplexing on an illumina iseq ( cycle flow cell). in new zealand, the artic network protocol was used for wgs (quick ) . in short, -bp tiling amplicons designed with primal scheme (grubaugh et al. a ) were used to amplify viral cdna prepared with superscript iii. a sequence library was then constructed using the oxford nanopore ligation sequencing kit and sequenced on a r . . minion flow cell. near-complete viral genomes were then assembled de novo in geneious prime . . or through reference mapping with rampart v . . (hadfield ) using the artic network ncov- novel coronavirus bioinformatics protocol (loman and rambaut ) . in total, sars-cov- genomes were sequenced from cases in nsw diagnosed between january and march , as well as a single genome from the first patient in auckland, new zealand sampled on february (table ) . australian and new zealand sequences were aligned to global reference strains sourced from gisaid with mafft (katoh ) and then compared phylogenetically using a maximumlikelihood approach-phyml v . . (guindon and gascuel ) . the australian strains of sars-cov- were dispersed across the global sars-cov- phylogeny (fig. a) . the first four cases of covid- disease in nsw occurred between and january , and these were closely related with - single nucleotide polymorphisms (snps) difference to the dominant variant circulating in wuhan at the time (prototype strain mn /sars-cov- /wuhan-hu- ). as the four patients identified in this period had recently returned from china, this region was the likely source of infection. from february , travel to australia from mainland china was restricted to returning australian residents and their children, who were placed in home quarantine for days. despite the intensive testing of such returning travellers, no further cases of covid- were detected in nsw until february , when sars-cov- was detected in an individual returning from iran (nsw ). a close contact of this individual also tested positive (nsw ) providing the first evidence of local transmission within nsw. this was followed by further iran travel-linked cases in nsw (nsw , nsw , nsw , and nsw ) and new zealand (nz ). of note, the genomes of all patients with a history of travel to iran were part of a monophyletic group defined by three nucleotide substitutions (g a, t c, and g t) in the sars-cov- genome relative to the wuhan prototype strain (fig. b) . g a and t c both occur in coding regions with g a producing a non-synonymous change (v i) in the orf ab-encoded non-structural protein region. g t occurs in the -utr. in addition to the australian and new zealand strains, this clade also included a traveller who had returned to canada from iran (bc_ _ - ), providing further evidence of its likely link to the iranian epidemic. indeed, a search of all currently available gisaid sequences and metadata revealed no other complete genome sequences from patients with documented history of travel to or residence in iran (as of march ). a search of partial sequences identified two sars-cov- sequences which originated in iran ( /irn/ tehran aw/ - - and /irn/tehran be/ - - ) spanning a nt region of the viral nucleoprotein (n). although short in length, these two sequences covered one of the informative snps defining this clade-t c, and both iranian strains matched the sequences from patients with travel histories to iran and grouped by phylogenetic analysis (supplementary figs. s and s ). technological advancements and the widespread adoption of wgs in pathogen genomics have transformed public health and infectious disease outbreak responses (popovich and snitkin ) . previously, disease investigations often relied on the targeted sequencing of a small locus to identify genotypes and infer patterns of spread along with epidemiological data (dudas and bedford ) . as seen with the recent west african ebola (dudas et al. ) and zika virus epidemics (grubaugh et al. ) , rapid wgs significantly increases resolution of diagnosis and surveillance thereby strengthening links between genomic, clinical, and epidemiological data (grenfell ) , and potentially uncovering outbreaks in unsampled locations (grubaugh et al. b ). this advance improves our understanding of pathogen origins and spread that ultimately lead to stronger and more timely intervention and control measures (grubaugh et al. c) . following the first release of the sars-cov- genome (wu et al. ) , public health and research laboratories worldwide have rapidly shared sequences on public data repositories such as gisaid (shu and mccauley ) (n ¼ genomes as of march ) that have been used to provide near real-time snapshots of global diversity through public analytic and visualization tools (hadfield et al. ) . although all known cases linked to iran are contained in this clade, it is important to note the presence of two chinese strains sampled during mid-january from hubei and shandong provinces. it is expected that further chinese strains will be identified that fall in this clade, and across the entire phylogenetic diversity of sars-cov- as this is where the outbreak started, including likely for the outbreak in iran itself. however, while we cannot completely discount that the cases in australia and new zealand came from other sources including china, our phylogenetic analyses, as well as epidemiological (recent travel to iran) and clinical data (date of symptom onset), provide evidence that this clade of sars-cov- is directly linked to the iranian epidemic, from where genomic data are currently lacking. importantly, the seemingly multiple importations of very closely related viruses from iran into australia suggest that this diversity reflects the early stages of sars-cov- transmission within iran. supplementary data are available at virus evolution online. evolution of human respiratory syncytial virus (rsv) over multiple seasons in new south wales an interactive web-based dashboard to track covid- in real time the ability of single genes vs full genomes to resolve time and space in outbreak analysis virus genomes reveal factors that spread and sustained the ebola epidemic unifying the epidemiological and evolutionary dynamics of pathogens an amplicon-based sequencing framework for accurately measuring intrahost virus diversity using primalseq and ivar a simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood nextstrain: real-time tracking of pathogen evolution mafft: a novel method for rapid multiple sequence alignment based on fast fourier transform genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding whole genome sequencing-implications for infection prevention and outbreak investigations gisaid: global initiative on sharing all influenza data-from vision to reality b) coronavirus disease (covid- ) technical guidance: laboratory testing for a new coronavirus associated with human respiratory disease in china briefing on the current pneumonia epidemic situation in our city the members of the ncov- study group also include linda donovan, shanil kumar, tyna tran, danny ko, christine ngo, tharshini sivaruban, verlaine timms, connie lam, mailie gall, karen-ann gray, rosemarie sadsad, and alicia arnott. the authors acknowledge the sydney informatics hub and the use of the university of sydney's high-performance computing cluster, artemis, and all the laboratories that have referred sars-cov- samples to the centre for infectious diseases and microbiology laboratory services, nsw health pathology -institute of clinical pathology and medical research, westmead hospital. we would finally like to thank all the authors who have kindly shared genome data on gisaid, and we have included a table (supplementary table s ) outlining the authors and institutes involved. data including the sequences in this study are available for download from https:// www.gisaid.org/. this study was supported by the prevention research support programme funded by the new south wales ministry of health and the nhmrc centre of research excellence in emerging infectious diseases (gnt ).conflict of interest: none declared. key: cord- - rgz t authors: radandt, siegfried; rantanen, jorma; renn, ortwin title: governance of occupational safety and health and environmental risks date: journal: risks in modern society doi: . / - - - - _ sha: doc_id: cord_uid: rgz t occupational safety and health (osh) activities were started in the industrialized countries already years ago. separated and specific actions were directed at accident prevention, and the diagnosis, treatment and prevention of occupational diseases. as industrialization has advanced, the complexity of safety and health problems and challenges has substantially grown, calling for more comprehensive approaches. such development has expanded the scope, as well as blurred the borders between specific activities. in the modern world of work, occupational safety and health are part of a complex system that involves innumerable interdependencies and interactions. these are, for instance, safety, health, well-being, aspects of the occupational and general environment, corporate policies and social responsibility, community policies and services, community social environment, workers’ families, their civil life, lifestyles and social networks, cultural and religious environments, and political and media environments. a well-functioning and economically stable company generates resources to the workers and to the community, which consequently is able to maintain a positive cycle in development. a high standard of safety and health brings benefits for everyone: the company, the workers and the whole community. these few above-mentioned interactions elucidate the need for an integrated approach, and the modelling of the complex entity. if we picture osh as a house, this integrated approach could be the roof, but in order to build a stable house, it is also necessary to construct a solid basement as a foundation to the house. these basement "stones" are connected to each other, and are described in more detail in sections . - . . section . focuses on the existing hazards, while section . mainly considers the exposure of workers to health hazards. health, due to its complexity, however, is not only influenced and impaired by work-related hazards, but also by hazards arising from the environment. these two sub-chapters are thus linked to section . . in addition, the safety levels of companies may affect the environment. the strategies and measures needed for effective risk management, as described in section . , therefore also contribute to reducing the risks to the environment. in the case of work that is done outdoors, the hazards arising from the environment understandably have to be given special attention. here, the methods applied to tackle the usual hazards at workplaces are less effective. it is necessary to develop protective measures to avoid or minimize hazards present in the environment. namely, agriculture, forestry and construction involve these types of hazards, and affect high numbers of workers on a global scale. finally, hazards in the environment or in leisure-time activities can lead to strain and injuries which -combined with hazards at work -may result in more severe health consequences. as an example one can mention the hazardous substances in the air causing allergies or other illnesses. another example is the strain on the musculoskeletal system from sports and leisuretime activities causing low back pain and other musculoskeletal disorders. depending on the type of hazard, the three topics, namely, safety, health and the environment, may share the common trait that the proper handling of risks, i.e., how to reduce probabilities and/or consequences of unwanted events is not always possible within a risk management system. this is true when one moves into the realm of uncertainty, i.e., when there is uncertain, insufficient or no knowledge of the consequences and/or probabilities (see chapter ). . integrated multi-sectorial bodies for policy design and planning (national safety and health committee). . comprehensive approach in osh activities. . multi-disciplinary expert resources in inspection and services. . multi-professional participation of employers' and workers' representatives. . joint training in integrated activities. . information support facilitating multi-professional collaboration. international labour office (ilo) ( ) international labour conference, st session, report vi, ilo standards-related activities in the area of occupational safety and health: an in-depth study for discussion with a view to the elaboration of a plan of action for such activities. sixth item on the agenda. international labour office, geneva. what are the main challenges arising from the major societal changes for business/companies and workers/employees? how can these challenges be met in order to succeed in the growing international competition? what is the role of occupational safety and health (osh) in this context? the above-mentioned changes create new possibilities, new tasks and new risks to businesses in particular, and to the workers as well. in order to optimize the relation between the possibilities and the risks (maximize possibilities -minimize risks) there is a growing need for risk management. risk management includes all measures required for the target-oriented structuring of the risk situation and safety situation of a company. it is the systematic application of management strategies for the detection, assessment, evaluation, mastering and monitoring of risks. risk management was first considered exclusively from the point of view of providing insurance coverage for entrepreneurial risks. gradually the demands of jurisdiction grew, and the expectations of users and consumers increased with regard to the quality and safety of products. furthermore, the ever more complex problems of modern technology and ultimately the socioeconomic conditions have led to the development of risk management into an independent interdisciplinary field of work. risks can be regarded as potential failures, which may decrease trust in realizing a company's goals. the aim of risk management is to identify these potential failures qualitatively and quantitatively, and to reduce them to the level of a non-hazardous and acceptable residual risk potential. the development and formulation of a company's risk policy is regarded as the basis of effective risk management. this includes, first and foremost, the management's target concept with respect to the organization of work, distribution of labour, and competence of the departments and persons in charge of risk management. risk issues are important as far as acceptance of technology is concerned. it is not enough to reduce the problem to the question of which risks are tolerable or acceptable. it appears more and more that, although the risks themselves are not accepted, the measures or technologies causing them are. value aspects have an important role in this consideration. a positive or negative view of measures and technologies is thus influenced strongly by value expectations that are new, contradictory and even disputed. comparing risks and benefits has become a current topic of discussion. the relation between risks and benefits remains an unanswered question. the general public has a far broader understanding of the risks and benefits of a given technology than the normal understanding professed by engineering sciences which is limited to probability x harm. the damage or catastrophe potential, qualitative attributes such as voluntary nature and controllability also play an important role in the risk assessment of a technology. a normative setting for a certain, universally accepted risk definition according to engineering science is therefore hardly capable of consensus at the moment. the balanced management of risks and possibilities (benefits) is capable of increasing the value of a company. it may by far surpass the extent of legal obligations: for example, in germany, there is a law on the control and transparency for companies (kontrag) . the respective parameters may be defined accurately as follows: • strategic decisions aim to offer opportunities for acquiring benefit, taking into consideration risks. • risks that can have negative consequences to the technological capacities, the profitability potential, the asset values and the reputation of a company, as well as the confidence of shareholders are identified and measured. • the management focuses on important possibilities and risks, and addresses them adequately or reduces them to a tolerable level. the aim is not to avoid risks altogether, but to create opportunities for promoting proactive treatment of all important risks. the traditional occupational health hazards, such as physical, chemical and biological risks, as well as accidents, will not totally disappear as a consequence of change, nor will heavy physical work. about - % of workers are still exposed to such hazards. there is thus need to still develop risk assessment, prevention and control methods and programmes for these often well-known hazards. in many industrialized countries, prevention and control programmes have had a positive impact by reducing the trends of occupational diseases and accidents, particularly in big industries. some developing countries, however, show an increase in traditional hazards. international comparisons, however, are difficult to make because of poor coverage, underreporting, and poor harmonization of concepts, definitions and registration criteria. statistics on occupational accidents are difficult to compare, and therefore data on their total numbers in europe should be viewed with caution. the majority of countries, however, have shown declining trends in accident rates irrespective of the absolute numbers of accidents. some exceptions to this general trend have nevertheless been seen. the accident risk also seems to shift somewhat as regards location, so that instead of risks related to machines and tools, particularly the risks in internal transportation and traffic within the workplace grow in relative importance. this trend may increase in future, particularly as the work place, as well as the speed and volume of material flows are increasing. a threat is caused by lengthened working hours, which tend to affect the vigilance of workers and increase the risk of errors. small-scale enterprises and micro-enterprises are known to have a lower capacity for occupational health and safety than larger ones. in fact, a higher accident risk has been noted in medium-sized companies, and a lower risk in very small and very large enterprises. we can conclude that this is due to the higher mechanization level and energy use in small and medium-sized enterprises (sme) compared with micro-enterprises, which usually produce services. on the other hand, the better capacity of very large enterprises in safety management is demonstrated by their low accident rates. the production of chemicals in the world is growing steadily. the average growth has been between - % a year during the past - decades. the total value of european chemical production in was about usd billion, i.e. % of the world's total chemical production, and it has increased % in the -year period of - . the european union (eu) is the largest chemical producer in the world, the usa the second, and japan the third. there are some , different chemical entities in industrial use, but only about , are so-called high-production volume (hpv) chemicals produced (and consumed) in amounts exceeding , tons a year. the number of chemicals produced in amounts of - , tons a year is about , . but volume is not necessarily the most important aspect in chemical safety at work. reactivity, toxicological properties, and how the chemicals are used, are more important. the european chemical companies number some , , and in addition there are , plants producing plastics and rubber. surprisingly, as many as % of these are smes employing fewer than workers, and % are micro-enterprises employing fewer than workers. thus, the common belief that the chemical industry constitutes only large firms is not true. small enterprises and self-employed people have much less competence to deal with chemical risk assessment and management than the large companies. guidance and support in chemical safety is therefore crucial for them. the number of workers dealing with chemicals in the european work life is difficult to estimate. the chemical industry alone employs some . million workers in europe, i.e. about % of the workforce of manufacturing industries. about %, i.e. over , work in chemical smes. but a much higher number of workers are exposed in other sectors of the economy. there is a distinct trend showing that the use of chemicals is spreading to all sectors, and thus exposures are found in all types of activities: agriculture, forestry, manufacturing, services and even in high-tech production. the national and european surveys on chemical exposures in the work environment give very similar results. while about % of the eu work-ers were exposed to hazardous chemicals, the corresponding figure in central and eastern european countries may be much higher. the workers are exposed simultaneously to traditional industrial chemicals, such as heavy metals, solvents and pyrolytic products, and to "new exposures", such as plastics monomers and oligomers, highly reactive additives, cross-linkers and hardeners, as well as to, for example, fungal spores or volatile compounds in contaminated buildings. this implies that some million people in the eu are exposed at work, and usually the level of exposure is one to three orders of magnitude higher than in any other environment. about the same proportion ( % of the workforce, i.e. , ) of the finnish workers in the national survey reported exposure. the chemicals to which the largest numbers of workers are exposed occur typically in smes; they are e.g. detergents and other cleaning chemicals, carbon monoxide, solvents, environmental tobacco smoke, and vegetable dusts. european directives on occupational health and safety require a high level of protection in terms of chemical safety in all workplaces and for all workers. risk assessment and risk management are key elements in achieving these requirements. the risk assessment of chemicals takes place at two levels: a) systems-level risk assessment, providing a dose-response relationship for a particular chemical, and serving as a basis for standard setting. risk assessment at the systems level is carried out in the pre-marketing stage through testing. this consequently leads to actions stipulated in the regulations concerning standards and exposure limits, labelling and marking of hazardous chemicals, limitations in marketing, trade and use. in this respect, the level of safety aimed at remains to be decided. is it the reasonably achievable level or, for example, the level achieved by the best available technology? the impact is expected to be system-wide, covering all enterprises and all workers in the country. this type of risk assessment is an interactive practice between the scientific community and the politically controlled decision making. a high level of competence in toxicology, occupational hygiene and epidemiology is needed in the scientific community. and the decision makers must have the ability to put the risk in concern into perspective. in most countries the social partners also take part in the political decision making regarding occupational risks. b) workplace risk assessment directed at identifying the hazards at an individual workplace and utilizing standards as a guide for making decisions on risk management. risk assessment at workplace level leads to practical actions in the company and usually ensures compliance with regulations and standards. risk assessment is done by looking at the local exposure levels and comparing these with standards produced in the type a) risk assessment. risk management is done through preventive and control actions by selecting the safest chemicals, by controlling emissions at their source, by general and local ventilation, and by introducing safe working practices. if none of the above is effective, personal protective devices must be taken into use. noise is a nearly universal problem. the products of technology, which have freed us from the day-to-day survival struggle, have been accompanied by noise as the price of progress. however, noise can no longer be regarded as an inevitable by-product of today's society. not only is noise an undesirable contaminant of our living environment, but high levels of noise are frequently present in a variety of work situations. many problems arise from noise: annoyance, interference with conversation, leisure or sleep, effects on work efficiency, and potentially harmful effects, particularly on hearing. in short, noise may affect health, productivity, and well-being. the selection of appropriate noise criteria for the industry depends on knowledge of the effects of noise on people, as well as on the activities in which they are engaged. many of the effects are dependent on the level, and the magnitude of the effects varies with this level. hearing damage is not the only criterion for assessing excessive noise. it is also important to consider the ability and ease of people to communicate with each other. criteria have therefore been developed to relate the existing noise environment to the ability of the typical individual to communicate in areas that are likely to be noisy. the effects of noise on job performance are difficult to evaluate. in general, one can say that sudden, intermittent, high-intensity noise impedes efficient work more than low-intensity and steady-state noise. the complexity of the task with which noise interferes plays a major role in determining how much noise actually degrades performance. two common ways in which noise can interfere with sleep are: delaying the onset of sleep, and shifting sleep stages. one effect of noise that does not seem to depend strongly on its level is annoyance. under some circumstances, a dripping water faucet can be as annoying as a jackhammer. there are no generally accepted criteria for noise levels associated with annoyance. if the noise consists of pure tones, or if it is impulsive in nature, serious complaints may arise. new information and communication technologies (ict) are being rapidly implemented in modern work life. about % of workers have computers at work, and about % are e-mail and internet users. there are three main problem areas in the use of new ict at work. these are: ) the visual sensory system, ) the cognitive processes, and ) the psychomotoric responses needed for employing hand-arm systems. all three have been found to present special occupational health and even safety problems, which are not yet fully solved. the design of new more user-friendly technology is highly desirable, and the criteria for such technology need to be generated by experts in neurophysiology, cognitive psychology and ergonomics. it is important to note that the productivity and quality of information-intensive work requiring the use of ict depends crucially on the user-friendliness of the new technology interface, both the hardware and software. communication and information technologies will change job contents, organization of work, working methods and competence demands substantially in all sectors of the economy in all countries. a number of new occupational health and safety hazards have already arisen or are foreseen, including problems with the ergonomics of video display units, and musculoskeletal disorders in shoulder-neck and arm-hand systems, information overload, psychological stress, and pressure to learn new skills. the challenge to occupational health and safety people is to provide health-based criteria for new technologies and new types of work organization. it is also important to contribute to the establishment of healthy and safe work environments for people. in the approved and draft standards of the international standardization organization, iso, there are altogether about different targets dealing with the standardization of eyesight-related aspects. vision is the most important channel of information in information-intensive work. from the point of view of seeing and eye fatigue, the commonly used visual display units (vdu) are not the most optimal solutions. stability of the image, poor lighting conditions, reflections and glare, as well as invisible flicker, are frequent problems affecting vision. the displays have, however, developed enormously in the s, and there is evidence that the so-called flat displays have gradually gained ground. information-intensive work may increasingly load the vision and sense of hearing, particularly of older workers. even relatively minor limitations in vision or hearing associated with ageing have a negative effect on receiving and comprehending messages. this affects the working capacity in information-intensive work. the growing haste in information-intensive work causes concern among workers and occupational health professionals. particularly older workers experience stress, learning difficulties and threat of exclusion. corrective measures are needed to adjust the technology to the worker. the most important extension of the man-technology interface has taken place in the interaction of two information-processing elements: the central nervous system and the microprocessor. the contact is transmitted visually and by the hands, but also by the software which has been developed during the s even more than the technology itself. many problems are still associated with the immaturity of the software, even though its user-friendliness has recently greatly improved. the logic and structure of the software and the user systems, visual ergonomics, information ergonomics, the speed needed, and the forgiving characteristics of programs, as well as the possibility to correct the commands at any stage of processing are the most important features of such improvements. also the user's skills and knowledge of information technology and the software have a direct effect on how the work is managed and how it causes workload. the user-friendliness and ergonomics of the technology, the disturbing factors in the environment, haste and time pressure, the work climate, and the age and professional skills of the individual user, even his or her physical fitness, all have an impact on the cognitive capacity of a person. this capacity can to a certain extent be improved by training, exercise and regulating the working conditions, as well as with expert support provided for the users when difficulties do occur. the use of new technologies has been found to be associated with high information overload and psychological stress. the problem is not only typical for older workers or those with less training, but also for the super-experts in ict who have shown an elevated risk of psychological exhaustion. there are four main types of ergonomic work loads: heavy dynamic work that may overload both the musculoskeletal and cardiovascular system; re-petitive tasks which may cause strain injuries; static work that may result in muscular pain; and lifting and moving heavy loads, which may result in overexertion, low back injury, or accidental injuries. visual ergonomics is gaining in importance in modern work life. the overload of the visual sensory system and unsatisfactory working conditions may strain the eye musculature, but can also cause muscle tension in the upper part of the body. this effect is aggravated if the worker is subjected to psychological stress or time pressure. in addition to being a biological threat, the risk of infections causes psychological stress to workers. the improved communication between health services and international organizations provides help in the early detection and control of previously unknown hazards. nevertheless, for example, the danger related to drug abusers continues to grow and present a serious risk to workers in, for example, health services and the police force. some new viral or re-emerging bacterial infections also affect health care staff in their work. the increase in the cases of drug-resistant tuberculosis is an example of such a hazard. the goal of preventive approaches is to exert control on the cause of unwelcome events, the course of such negative events or their outcome. in this context, one has to decide whether the harmful process is acute (an accident) or dependent on impact duration and stimulus (short-, medium-, and long-term). naturally, the prevention approaches depend on the phases of the harmful process, i.e. whether the harm is reversible, or whether it is possible only to maintain its status, or to slow down the process. it is assumed here that a stressful factor generates an inter-individual or intra-individual strain. thus the effects and consequences of stress are dependent on the situation, individual characteristics, capabilities, skills and the regulation of actions, and other factors. the overall consideration is related to work systems characterized by work contents, working conditions, activities, and actions. system performance is expected of this work system, and this system performance is characterized by a performance structure and its conditions and requirements (figure . ). the performance of the biopsychosocial unit, i.e. the human being, plays an important role within the human performance structure (see figures . and . ). the human being is characterized by external and internal features, which are closely related to stress compatibility, and thus to strain. in this respect, preventive measures serve to optimize and ensure performance, on the one hand, and to control stress and strain, on the other. preventive measures aim to prevent bionegative effects and to facilitate and promote biopositive responses. • the internal factors affecting performance are described by performance capacity and performance readiness. • performance capacity is determined by the individual's physiological and psychological capacity. • performance readiness is characterized by physiological fitness and psychological willingness. • the external factors affecting performance are described by organizational preconditions/requirements and technical preconditions/requirements. • regarding the organizational requirements, the organizational structure and organizational dynamics are of significance. • in the case of technical requirements, the difficulties of the task, characterized by machines, the entire plant and its constructions, task content, task design, technical and situation-related factors, such as work layout, anthropometrics, and quality of the environment, are decisive (table . ). mental stress plays an increasing role in the routine activities of enterprises. through interactive models of mental stress and strain, it is possible to represent the development of mental strain and its impairing effects (e.g. tension, fatigue, monotony, lack of mental satisfaction). it is important to distinguish the above-mentioned impairing effects from each other, since they can arise from different origins and can be prevented or eliminated by different means. activities that strain optimally enhance health and promote safe execution of work tasks. stress essentially results from the design parameters of the work system or workplace. these design parameters are characterized by, e.g.: • technology, such as work processes, work equipment, work materials, work objects; • anthropometric design; • work techniques, working hours, sharing of work, cycle dependence, job rotation; • physiological design that causes strain, fatigue; • psychological design that either motivates or frustrates; • information technology, e.g. information processing, cognitive ergonomic design; • sociological conditions; and • environmental conditions, e.g. noise, dust, heat, cold. the stress structure is very complex, and we therefore need to look at the individual parameters carefully, taking into account the interactions and links between the parameters at the conceptual level. the design parameters impact people as stress factors. as a result, they also turn into conditions affecting performance. such conditions can basically be classified into two types: a person's internal conditions, characterized in particular by predisposition and personality traits, and a person's external conditions, determined mainly by the design parameters. when we look at performance as resulting from regulated or reactive action, we find three essential approaches for prevention: • the first approach identifies strain. it is related to anatomical, biochemical, histological, physiological characteristic values, typical curves of organ systems, the degree of utilization of skills through stress, and thus the degree of utilization of the dynamics of physiological variables in the course of stress. • the second approach is related to the control of strain. the aim is to identify performance limits, the limits of training and practice, and to put them into positive use. adaptation and fatigue are the central elements here. • the third approach for prevention is related to reducing strain. the aim is to avoid harm, using known limits as guidelines (e.g. maximum workplace concentration limit values for harmful substances, maximum organspecific concentration values, biological tolerance values for substances, limit values for noise and physical loads). however, the use of guideline values can only be an auxiliary approach, because the stress-strain concept is characterized by highly complex connections between the exogenous stress and the resulting strain. an objectively identical stress will not always cause the same level of strain in an individual. due to action regulation and individual characteristic values and curves of the organ systems (properties and capabilities), differences in strain may occur. seemingly identical stress can cause differing strain due to the superposition of partial stress. combinations of partial stress can lead to compensatory differences (e.g. physiological stress can compensate for psychological stress) or accumulation effects. partial stress is determined by the intensity and duration of the stress, and can therefore appear in differing dimensions and have varying effects. in assessing overall stress, the composition of the partial stress according to type, intensity, course and time is decisive. partial stress can occur simultaneously and successively. in our considerations, the principle of homeostasis plays an important role. however, optimizing performance is only a means to an end in a prevention programme. the actual purpose is to avoid harm, and thus to control strain. harm is a bionegative effect of stress. the causative stress is part of complex conditions in a causal connection. causal relationships can act as dose-effect relationships or without any relation to the dose. in this respect, the causative stress condition can form a chain with a fixed or variable sequence; it can add up, multiply, intensify or have an effect in only specific combinations, and generate different effects (e.g. diseases). we are thus dealing with a multicausal model or a multi-factor genesis. low back pain is an example of a complex phenomenon. the incidence of musculoskeletal disorders, especially low back pain, is rapidly increasing. several occupational factors have been found to increase the risk for low back pain. some studies indicate that psychosocial and work-related conditions are far more accurate in the prognosis of disability than are physical conditions. chronic low back pain is perceived as a phenomenon which encompasses biological, social and psychological variables. according to the model of adaptation, the goal of reducing risks is to increase a person's physical abilities (i.e. flexibility, strength, endurance), the use of body mechanics, techniques to protect the back (following the rules of biomechanics), to improve positive coping skills and emotional control. the following unfavourable factors leading to back pain have been identified at workplaces: • the lifting of too heavy loads. • working in a twisted or bent-down position. • work causing whole-body vibration. • working predominantly in a sitting position. • carrying heavy loads on the shoulders. the prevention of acute back pain and the prevention of work disability must entail several features. one important element is work safety, which can be maximized by screening a worker's physical and intellectual capacities, by ensuring ergonomic performance of the work procedures, and by increasing awareness of proper working techniques that do not strain the back. the use of adaptation programmes makes it possible to attain a higher performance level and to be able to withstand more strain (figure . ) . research-based methods of training optimize and improve performance. they are a means for controlling stress and strain with the aim of preventing bionegative effects and facilitating and promoting biopositive responses. the stress (load) and strain model and human performance can be described as follows: • causative stress generates an inter-individual or intra-individual strain. • the effects and consequences depend on a person's properties, capabilities, skills and the regulation of actions, individual characteristics of the organ systems, and similar factors. • within the performance structure, the performance of the biopsychosocial unit, i.e. the human being, plays an important role. the human being is characterized by external and internal factors, which in turn are closely related to stress compatibility and thus to strain. the connection between stress and harm plays a significant role in the research on occupational health hazards. how should this connection be explored? different hypotheses exist in replying to this question, but none of them have been definitively proven. the three most common hypotheses today are: stress occurring in connection with a person's life events. the number and extent of such events is decisive. problem-coping behaviour and/or social conditions are variables explaining the connection between stress and harm. . the additive stress hypothesis. the ability to cope with problems and the social conditions has an effect on harm which is independent of the stress resulting from life events. when we refer to the complexity of risks in this context of occupational safety our focus shall be on the enterprise. there are different kinds of risks to be found in enterprises. many of them are of general importance, i.e. they are in principle rather independent of an enterprise's size or its type of activity. how to deal with such risks shall be outlined to some extent here. in order to treat those risks at work successfully resources are needed whose availability often depends on the enterprise's situation. the situation in enterprises usually is a determining indicator for available resources to control and develop safety and health and thus performance of the enterprise and its workers and employees through appropriate preventive measures. this situation has been described to some extent in chapter . big companies usually have well-developed safety and health resources, and they often transfer appropriate policies and practices to the less developed areas where they operate. even in big enterprises, however, there is fragmentation of local workplaces into ever smaller units. many of the formerly in-built activities of enterprises are outsourced. new types of work organizations are introduced, such as flat and lean organizations, increase of telework and call centres, many kinds of mobile jobs and network organizations. former in-company occupational health services are frequently transferred to service providers. this leads to the establishment of high numbers of micro-enterprises, small scale enterprises (sses), small and medium-sized enterprises (smes) and self-employed people. sses and smes are thus becoming the most important employers in the future. from a number of studies there is evidence that at least among a part of sses and smes awareness of osh risks is low. both managers and workers often do not see the need to improve occupational safety and health or ergonomic issues and their possibilities and benefits by reducing or eliminating risks at work. as these types of enterprises, even more the self-employed, do not have sufficient resources or expertise for implementing preventive measures, the need for external advisory support, services and incentives is evident and growing. interpersonal relations in sses and smes being generally very good provides a strong chance for effectively supporting them. other special features in the structure of small and medium-sized enterprises to be considered are: • direct participation of the management in the daily activities; • the management structure is designed to meet the requirements of the manager; • less formal and standardized work processes, organizational structures and decision processes; • no clear-cut division of work: -wide range of tasks; and -less specialization of the employees; • unsystematic ways of obtaining and processing information; • great importance of direct personal communication; • less interest in external cooperation and advice; • small range of internal, especially long-term and strategic planning; and • stronger inclination of individual staff members to represent their own interests. the role of occupational health services (ohs) in smes is an interdisciplinary task, consisting of: • risk assessment: -investigation of occupational health problems according to type of technology, organization, work environment, working conditions, social relationships. • surveillance of employees' health: -medical examinations to assess employees' state of health; and -offering advice, information, training. • advice, information, training: -measures to optimize safety and health protection; and -safe behaviour, safe working procedures, first aid preparedness. different kinds of risks are found in enterprises (see table . ). these different types of risks need to be handled by an interlinked system to control the risks and to find compromises between the solutions. figure . illustrates these linkages. the promotion of safety and health is linked to several areas and activities. all of these areas influence the risk management process. the results of risk treatment not only solve occupational health and safety problems, but they also give added value to the linked fields. specific risk management methods are needed to reach the set goal. one needs to know what a risk is. the definition of risk is essential: a risk is a combination of a probability -not frequency -of occurrence, and the associated unwelcome outcome or impact of a risk element (consequence). risk management is recognized as an integral part of good management practice. it is a recurring process consisting of steps which, when carried out in a sequence, allow decision making to be improved continuously. risk management is a logical and systematic method of identifying, analyzing, evaluating, treating, monitoring and communicating risks arising during any activity, function, or process in a manner enabling the organization to minimize losses and maximize productive opportunities. different methods are available for analyzing problems. each method is especially suited to respond to certain questions and less suited for others. a complex "thinking scheme" is necessary for arranging the different analyses correctly within the system review. such a scheme includes the following steps: . defining the unit under review: the actual tasks and boundaries of the system (a fictitious or a real system) must be specified: time, space and state. . problem analysis: all problems existing in the defined system, including problems which do not originate from the system itself, are detected and described. . causes of problems: all possible or probable causes of the problems are identified and listed. . identifying interaction: the dependencies of the effect mechanisms are described, and the links between the causes are determined. . establishing priorities and formulating targets: to carry out this step, it is necessary to evaluate the effects of the causes. . solutions to the problems: all measures needed for solving the individual problems are listed. the known lists usually include technical as well as non-technical measures. since several measures are often appropriate for solving one problem, a pre-selection of measures has to be done already at this stage. however, this can only be an approach to the solution; the actual selection of measures has to be completed in steps and . . clarifying inconsistencies and setting priorities: as the measures required for solving individual problems may be inconsistent in part, or may even have to be excluded as a whole, any inconsist-encies need to be clarified. a decision should then be made in favour or against a measure, or a compromise may be sought. . determining measures for the unit under review: the measures applicable to the defined overall system are now selected from the measures for the individual problems. . list of questions regarding solutions selected for the overall system: checking whether the selected measures are implementable and applicable for solving the problems of the overall system. . controlling for possible new problems: this step consists of checking whether new problems are created by the selected solution. the close link between cause and effect demands that the processes and sub-processes must be evaluated uniformly, and risks must be dealt with according to a coordinated procedure. the analysis is started by orientation to the problem. this is done in the following steps: . recognizing and analyzing the problem according to its causes and extent, by means of a diagnosis and prediction, and comparison with the goals aimed at. . description and division of the overall problem into individual problem areas, and specifying their dependencies. . defining the problem and structuring it according to the objectives, time relation, degree of difficulty, and relevance to the goal. . detailed analysis of the causes, and classification in accordance to the possible solution. the analysis of the problem should be integrated into the overall analytical process in accordance with the thinking schemes described earlier. the relevance and priorities related to the process determine the starting point for the remaining steps of the analysis. analyses are divided into quantitative and qualitative ones. quantitative analyses include risk analyses, that is, theoretical safety-related analysis methods and safety analyses, e.g. classical accident analyses. qualitative analyses include failure mode and effect analyses, hazard analyses, failure hazard analyses, operating hazard analyses, human error code and effect analyses, information error and effect analyses. the theoretical safety-related analysis methods include inductive and deductive analyses based on boolean models. inductive analyses are, e.g. fault process analyses. deductive analyses are fault tree analyses, analytical processes and simulation methods. theoretical safety-related analysis methods which are not based on boolean models are stochastic processes, such as markow's model, risk analyses and accident analyses which, as a rule, are statistical or probability-related analyses. a possible scheme to begin with is shown in figure . . since absolute safety, entailing freedom from all risks, does not exist in any sphere of life, the task of those dealing with safety issues is to avert hazards and to achieve a sustainable reduction of the residual risk, so that it does not exceed a tolerable limit. the extent of this rationally acceptable risk is also influenced by the level of risk which society intuitively considers as being acceptable. those who propose definitions of safety are neither authorized nor capable of evaluating the general benefit of technical products, processes and services. risk assessment is therefore focused at the potential harm caused by the use or non-use of the technology. the guidelines given in "a new approach to technical harmonization and standards" by the council resolution of may are valid in the european union. the legal system of a state describes the protective goals, such as protection of life, health, etc., in its constitution, as well as in individual laws and regulations. as a rule, these do not provide an exact limit as to what is still a tolerable risk. this limit can only be established indirectly and unclearly on the basis of the goals and conceptions set down by the authorities and laws of a state. in the european union, the limits are expressed primarily in the "basic safety and health requirements". these requirements are then put into more concrete terms in the safety-related definitions issued by the bodies responsible for preparing industrial standards. compliance with the standards is voluntary, but it is presumed that the basic requirements of the directives are met. the term which is opposite to "safety" is "hazard". both safe and hazardous situations are founded on the intended use of the technical products, processes and services. unintended use is taken into account only to the extent that it can be reasonably foreseen. the risks present in certain events are, in a more narrow sense, unwelcome and unwanted outcomes with negative effects (which exceed the range of acceptance). unwelcome events are • source conditions of processes and states; • processes and states themselves; and • effects of processes and states which can result in harm to persons or property. an unwelcome event can be defined as a single event or an event within a sequence of events. possible unwelcome events are identified for a unit under review. the causes may be inherent in the unit itself, or outside of it. in order to determine the risks involved in unwelcome events, it is necessary to identify probabilities and consequences. the question arises: are the extent and probability of the risk known? information is needed to answer this question. defining risk requires information concerning the probability of occurrence and the extent of the harm of the consequences. uncertainty is given if the effects are known but the probability is unknown. ignorance is given if both the effects and the probability are unknown. figure . shows the risk analysis procedure according to the type of information available. since risk analyses are not possible without practical, usable information, it is necessary to consider the nature of the information. the information is characterized by its content, truth and objectivity, degree of confirmation, the possibility of being tested, and the age of the information. the factors determining the content of the information are generality, precision and conditionality. the higher the conditionality, the smaller is the generality, and thus the smaller the information content of the statement. truth is understood as conformity of the statement with the real state of affairs. the closer that the information is to reality, the higher is its information content, and the smaller its logical margin. the degree of controllability is directly dependent on the information content: the bigger the logical margin, the smaller the information content, and thus the higher the probability that the information content will prove its worth. in this respect, probability plays a role in the information content: the greatest significance is attributed to the logical hypothetical probability and statistical probability of an event. objectivity and age are additional criteria for any information. the age and time relation of information play a particularly important role, because consideration of the time period is an important feature of analysis. as a rule, information and thus the data input in the risk analysis consist of figures and facts based on experience, materials, technical design, the organization and the environment. in this regard, most figures are based on statistics on incidents and their occurrences. factual information reveals something about the actual state of affairs. it consists of statements related to past conditions, incidents, etc. forecast-type predictions are related to real future conditions, foretelling that certain events will occur in the future. explanatory information replies to questions about the causes of phenomena, and provides explanations and reasons. it establishes links between different states based on presumed cause-effect relationships. subjunctive information expresses possibilities, implying that certain situations might occur at present or in the future, thus giving information about conceivable conditions, events and relationships. normative information expresses goals, standards, evaluations and similar matters; it formulates what is desirable or necessary. the main problem with risk analyses is incomplete information, in particular regarding the area of "uncertainty". in the eu commission's view, recourse to the so-called precautionary principle presupposes that potentially dangerous effects deriving from a phenomenon, product or process have been identified via objective scientific evaluation, and that scientific evaluation does not allow the risk to be determined with sufficient certainty. recourse to the precautionary principle thus takes place in the framework of general risk management that is concretely connected to the decision-making process. if application of the precautionary principle results in the decision that action is the appropriate response to a risk, and that further scientific information is not needed, it is still necessary to decide how to proceed. apart from adopting legal provisions which are subject to judicial control, a whole range of actions is available to the decision-makers (e.g. funding research, or deciding to inform the public about the possible adverse effects of a product or procedure). however, the measures may not be selected arbitrarily. in conclusion, the assessment of various risks and risk types which may be related to different types of hazards requires a variety of specific risk assessment methods. if one has dependable information about the probability and consequences of a serious risk or risky event, one should use the risk assessment procedure shown in figure . . • major industrial accidents; • damage caused by dangerous substances; • nuclear accidents; • major accidents at sea; • disasters due to forces of nature; and • acts of terrorism. • dangerous substances discharged (fire, explosion); • injury to people and damage to property; • immediate damage to the environment; • permanent or long-term damage to terrestrial habitats, to fresh water, to marine habitats, to aquifers or underground water supplies; and • cross-border damage. • technical failure: devices, mountings, containers, flanges, mechanical damage, corrosion of pipes, etc.; • human failure: operating error, organizational failure, during repair work; • chemical reaction; • physical reaction; and • environmental cause. system analysis is the basis of all hazard analyses, and thus needs to be done with special care. system analysis includes the examination of the system functions, particularly the performance goals and admissible deviations in the ambient conditions not influenced by the system, the auxiliary sources of the system (e.g. energy supply), the components of the system, and the organization and behaviour of the system. geographical arrangements, block diagrams, material flow charts, information flow charts, energy flow charts, etc. are used to depict technical systems. the objective is to ensure the safe behaviour of the technical systems by design methods, at least during the required service life and during intended use. qualitative analyses are particularly important in practice. as a rule, they are form sheet analyses and include failure mode and effect analyses, which examine and determine failure modes and their effects on systems. the preliminary hazard analysis looks for the hazard potentials of a system. the failure hazard analysis examines the causes of failures and their effects. the operating hazard analysis determines the hazards which may occur during operation, maintenance, repair, etc. the human error mode and effect analysis examines error modes and their effects which occur because of wrong behaviour of humans. the information error mode and effect analysis examines operating, maintenance and repair errors, fault elimination errors and the effects caused by errors in instructions and faulty information. theoretical analysis methods include the fault tree analysis, which is a deductive analysis. an unwelcome incident is provided to the system under review. then all logical links and/or failure combinations of components or partial system failures which might lead to this unwelcome incident are assembled, forming the fault tree. the fault tree analysis is suited for simple as well as for complex systems. the objective is to identify failures which might lead to an unwelcome incident. the prerequisite is exact knowledge about the functioning of the system under review. the process, the functioning of the components and partial systems therefore need to be present. it is possible to focus on the flow of force, of energy, of materials and of signals. the fault process analysis has a structure similar to that of the fault tree analysis. in this case, however, we are looking for all unwelcome incidents as well as their combinations which have the same fault trigger. analysis of the functioning of the system under review is also necessary for this. analyses can also be used to identify possible, probable and actual risk components. the phases of the analysis are the phases of design, including the preparation of a concept, project and construction, and the phases of use which are production, operation and maintenance. in order to identify the fault potential as completely as possible, different types of analyses are usually combined. documentation of the sufficient safety of a system can be achieved at a reasonable cost only for a small system. in the case of complex systems, it is therefore recommended to document individual unwelcome incidents. if solutions are sought and found for individual unwelcome incidents, care should be taken to ensure that no target conflicts arise with regard to other detail solutions. with the help of the fault tree, it is possible to analyse the causes of an unwelcome incident and the probability of its occurrence. decisions on whether and which redundancies are necessary can in most cases be reached by simple estimates. four results can be expected by using a fault tree: . the failure combination of inputs leading to the unwelcome event; . the probability of their occurrence; . the probability of occurrence of the unwelcome event; and . the critical path that this incident took from the failure combination through the fault tree. a systematic evaluation of the fault tree model can be done by an analytical evaluation (calculation) or by simulation of the model (monte-carlo method). a graphic analysis of the failure process is especially suited to prove the safety risk of previously defined failure combinations in the system. the failure mode and effect analysis and the preliminary hazard analysis as mentioned previously, no method can disclose all potential faults in a system with any degree of certainty. however, if one starts with the preliminary hazard analysis, then at least the essential components with hazard potential will be defined. the essential components are always similar, namely, kinetic energy, potential energy, source of thermal energy, radioactive material, biological material, chemically reactive substance. with the fault tree method, any possible failure combinations (causes), leading to an unwelcome outcome, can then be identified additionally. re- are especially suited for identifying failures in a system which pose a risk. liability parameters can be determined in the process, e.g. the frequency of occurrence of failure combinations, the frequency of occurrence of unwelcome events, non-availability of the system upon requests, etc. the failure effect analysis is a supplementary method. it is able to depict the effects of mistakes made by the operating personnel, e.g. when a task is not performed, or is performed according to inappropriate instructions, or performed too early, too late, unintentionally or with errors. it can pinpoint also effects resulting from operating conditions and errors in the functional process or its elements. an important aspect of all hazard analyses is that they are only valid for the respective case under review. every change in a parameter basically requires new analyses. this applies to changes in the personnel structure and the qualification of persons, as well as to technical specifications. for this reason, it is necessary to document the parameters on which each analysis is based. the results of the hazard analyses form the basis for the selection of protective measures and measures to combat the hazards. if the system is modified, the hazards inherent in the system may change, and the measures to combat the hazards may have to be changed as well. this may also mean that the protective measures or equipment which existed at time x for the system or partial system in certain operating conditions (e.g. normal operation, set-up operation, and maintenance phase) may no longer be compatible. different protective measures, equipment or strategies may then be needed. however, hazard analyses do not merely serve to detect and solve potential failures. they form the basis for the selection of protective measures and protective equipment, and they can also test the success of the safety strategies specified. a selection of methods used for hazard analysis is given in annex to section . . risk assessment is a series of logical steps enabling the systematic examination of the hazards associated with machinery. risk assessment is followed, whenever necessary, by actions to reduce the existing risks and by implementing safety measures. when this process is repeated, it eliminates hazards as far as possible. risk assessment includes: • risk analysis: -determining the limits of machinery; -identifying hazards; and -estimating risks. • risk evaluation. risk analysis provides the information required for evaluating risks, and this in turn allows judgements to be made on the safety of e.g. the machinery or plant under review. risk assessment relies on decisions based on judgement. these decisions are to be supported by qualitative methods, complemented, as far as possible, by quantitative methods. quantitative methods are particularly appropriate when the foreseeable harm is very severe or extensive. quantitative methods are useful for assessing alternative safety measures and for determining which measure gives best protection. the application of quantitative methods is restricted to the amount of useful data which is available, and in many cases only qualitative risk assessment will be possible. risk assessment should be conducted so that it is possible to document the used procedure and the results that have been achieved. risk assessment shall take into account: • the life cycle of machinery or the life span of the plant. • the limitations of the machinery or plant, including the intended use (correct use and operation of the machinery or plant, as well as the consequences of reasonably foreseeable misuse or malfunction). • the full range of foreseeable uses of the machinery (e.g. industrial, nonindustrial and domestic) by persons identified by sex, age, dominant hand usage, or limiting physical abilities (e.g. visual or hearing impairment, stature, strength). • the anticipated level of training, experience or ability of the anticipated users, such as: -operators including maintenance personnel or technicians; -trainees and juniors; and -general public. • exposure of other persons to the machine hazards, whenever they can be reasonably foreseen. having identified the various hazards that can originate from the machine (permanent hazards and ones that can appear unexpectedly), the machine designer shall estimate the risk for each hazard, as far as possible, on the basis of quantifiable factors. he must finally decide, based on the risk evaluation, whether risk reduction is required. for this purpose, the designer has to take into account the different operating modes and intervention procedures, as well as human interaction during the entire life cycle of the machine. the following aspects in particular must be considered: • construction; transport; • assembly, installation, commissioning; • adjusting settings, programming or process changeover; • instructions for users; • operating, cleaning, maintenance, servicing; and • checking for faults, de-commissioning, dismantling and safe disposal. malfunctioning of the machine due to, e.g. • variation in a characteristic or dimension of the processed material or workpiece; • failure of a part or function; • external disturbance (e.g. shock, vibration, electromagnetic interference); • design error or deficiency (e.g. software errors); • disturbance in power supply; and • flaw in surrounding conditions (e.g. damaged floor surface). unintentional behaviour of the operator or foreseeable misuse of the machine, e.g.: • loss of control of the machine by the operator (especially in the case of hand-held devices or moving parts); • automatic (reflexive) behaviour of a person in case of a machine malfunction or failure during operation; • the operator's carelessness or lack of concentration; • the operator taking the "line of least resistance" in carrying out a task; • behaviour resulting from pressure to keep the machine running in all circumstances; and • unexpected behaviour of certain persons (e.g. children, disabled persons). when carrying out a risk assessment, the risk of the most severe harm that is likely to occur from each identified hazard must be considered, but the greatest foreseeable severity must also be taken into account, even if the probability of such an occurrence is not high. this objective may be met by eliminating the hazards, or by reducing, separately or simultaneously, each of the two elements which determine the risk, i.e. the severity of the harm from the hazard in question, and the probability of occurrence of that harm. all protective measures intended to reach this goal shall be applied according to the following steps: this stage is the only one at which hazards can be eliminated, thus avoiding the need for additional protective measures, such as safeguarding machines or implementing complementary protective measures. . information about the residual risk. information for use on the residual risk is not to be a substitute for inherently safe design, or for safeguarding or complementary protective measures. risk estimation and evaluation must be carried out after each of the above three steps of risk reduction. adequate protective measures associated with each of the operating modes and intervention procedures prevent operators from being prone to use hazardous intervention techniques in case of technical difficulties. the aim is to achieve the lowest possible level of risk. the design process is an iterative cycle, and several successive applications may be necessary to reduce the risk, making the best use of available technology. four aspects should be considered, preferably in the following order: . the safety of the machine during all the phases of its life cycle; . the ability of the machine to perform its function; . the usability of the machine; and . the costs of manufacturing, operating and dismantling the machine. the following principles apply to technical design: service life, safe machine life, fail-safe and tamper-proof design. a design which ensures the safety of service life has to be chosen when neither the technical system nor any of its safety-relevant partial functions can be allowed to fail during the service life envisaged. this means that the components of the partial functions need to be exchanged at previously defined time intervals (preventive maintenance). in the case of a fail-safe design, the technical system or its partial functions allow for faults, but none of these faults, alone or in combination, may lead to a hazardous state. it is necessary to specify just which faults in one or several partial systems can be allowed to occur simultaneously without the overall system being transferred into a hazardous state (maximum admissible number of simultaneous faults). a failure or a reduction in the performance of the technical system is accepted in this case. tamper-proof means that it is impossible to intentionally induce a hazardous state of the system. this is often required of technical systems with a high hazard potential. strategies involving secrecy play a special role in this regard. in the safety principles described here, redundant design should also be mentioned. the probability of occurrence and the consequences of damage are reduced by multiple arrangements, allowing both for subsystems or elements to be arranged in a row or in parallel. it is possible to reduce the fault potential of a technical system by the diversification of principles: several different principles are used in redundant arrangements. the spatial distribution of the function carriers allows the possibilities to influence faults to be reduced to one function. in the redundant arrangements, important functions, e.g. information transmission, are therefore designed in a redundant manner at different locations. the measures to eliminate or avoid hazards have to meet the following basic requirements: their effect must be reliable and compulsory, and they cannot be circumvented. reliable effect means that the effect principle and construction design of the planned measure guarantee an unambiguous effect, that the components have been designed according to regulations, that production and assembly are performed in a controlled manner, and that the measure has been tested. compulsory effect includes the demand for a protective effect which is active at the start of a hazardous state and during it, and which is deactivated only when the hazardous state is no longer present, or stops when the protective effect is not active. technical systems are planned as determined systems. only predictable and intended system behaviour is taken into account when the system is designed. experience has shown, however, that technical systems also display stochastic behaviour. that is, external influences and/or internal modifications not taken into consideration in the design result in unintended changes in the system's behaviour and properties. the period of time until the unintended changes in behaviour and/or in properties occur, cannot be accurately determined; it is a random variable. we have to presume that there will be a fault in every technical system. we simply do not know in advance when it will take place. the same is true for repairs. we know that it is generally possible in systems requiring re-pair to complete a repair operation successfully, but we cannot determine the exact time in advance. using statistical evaluations, we can establish a timedependent probability at which a "fault event" or "completion of a repair operation" occurs. the frequency of these events determines the availability of the system requiring repair. technical systems are intended to perform numerous functions and, at the same time, to be safe. the influence of human action on safety has to be taken into account in safety considerations as well (i.e. human factor). a system is safe when there are no functions or action sequences resulting in hazardous effects for people and/or property. risks of unwelcome events (in the following called "risk of an event") are determined on the basis of the experience (e.g. catalogue of measures) with technical systems. in addition to this, safety analyses are used (e.g. failure mode and effect analysis, hazard analysis, failure hazard analysis, operating hazard analysis, information error analysis), as well as mathematical models (e.g. worst-case analysis, monte-carlo procedure, markow's models). unwelcome events are examined for their effects. this is followed by considerations about which design modifications or additional protective measures might provide sufficient safety against these unwelcome events. the explanations below present the basic procedure for developing safety-relevant arrangements and solutions, i.e. the thinking and decision-making processes, as well as selecting criteria that are significant for the identification of unwelcome events, the risk of an event, the acceptance limits and the adoption of measures. before preparing the final documentation, it is essential to verify that the limit risk has not been exceeded, and that no new unwelcome events have occurred. the sequence scheme describes the procedure for developing safety arrangements and for finding solutions aiming to avoid the occurrence of unwelcome events which exceed the acceptance limits, by selecting suitable measures. in this context, it is assumed that: • an unwelcome event is initially identified as a single event within a comprehensive event sequence (e.g. start-up of a plant), and the risk of an event and limit risk are determined. • the selection of technical and/or non-technical measures is subject to a review of the content and the system, and the decision regarding a solution is then made. • the number of applicable measures is limited, and therefore it may not be possible to immediately find a measure with an acceptable risk for a preliminary determination of the unwelcome event. • implementation of the selected solution can result in the occurrence of a new unwelcome event. • in the above cases, a more concrete, new determination of the unwelcome event and/or the unit under review, or the state of the unit under review, and another attempt at deciding upon measures may lead to the desired result, although this may have to be repeated several times before it is successful. in the case of complex event sequences, several unwelcome events may become apparent which have to be tackled by the respective set of measures. in accordance with the sequence scheme, the unit under review and its state have to be determined first. this determination includes information on, e.g., • product type, dimension, product parts/elements distinguished according to functional or construction aspects, if applicable; • intended use; • work system or field of application; • target group; • supply energy, transformed in the product, transmitted, distributed, output; • other parameters essential to safety assessment according to type and size of the product; • known or assumed effects on the product or its parts (e.g. due to transport, assembly, conditions at the assembly site, operation, maintenance); • weight, centre of gravity; • materials, consumables; • operating states (e.g. start-up, standstill, test run, normal operation); • condition (new, condition after a period in storage/shutdown, after repair, in case of modified operating conditions and/or other significant changes); and • known or suspected effects on humans. the next step is the identification of unwelcome events. they are source conditions of processes and states, or processes and states themselves. they can be the effects of processes and states which can cause harm to people or property. an unwelcome event can be a single event or part of a sequence of events. one should look for unwelcome events in sequences of processes and functions, in work activities and organizational procedures, or in the work environment. care has to be taken that the respective interfaces are included in the considerations. deviations and time-dependent changes in regard to the planned sequences and conditions have to be taken into account as well. the risk of an unwanted event results from the probability statement which takes into account both • the expected frequency of occurrence of the event; and • the anticipated extent of harm of the event. the expected frequency of occurrence of an event leading to harm is determined by, e.g., • the probability of the occurrence itself; • the duration and frequency of exposure of people (or of objects) in the danger zone, e.g. -extremely seldom (e.g. during repair), -seldom (e.g. during installation, maintenance and inspection), -frequently, and -very frequently (e.g. constant intervention during every work cycle); • the influence of users or third parties on the risk of an event. the extent of harm is determined by, e.g., • the type of harm (harm to people and/or property); • the severity of the harm (slight/severe/fatal injury of persons, or corresponding damage to property); and • number of people or objects affected. in principle, the safety requirements depend on the ratio of the risk of an event to the limit risk. criteria for determining the limit risk are, e.g., • personal and social acceptance of hazards; • people possibly affected (e.g. layman, trained person, specialized worker); • participation of those affected in the process; and • possibilities of averting hazards. the safety of various technical equipment with comparable risk can, for instance, be achieved • primarily by technical measures, in some cases; and • mainly by non-technical measures, in other cases. this means that several acceptable solutions with varying proportions of technical and non-technical measures may be found for a specific risk. in this context, the responsibility of those involved should be taken into consideration. technical measures are developed on the basis of e.g. the following principles: • avoiding hazardous interfaces (e.g. risk of crushing, shearing); hazard sources (e.g. radiation sources, flying parts, hazardous states and actions as well as inappropriate processes); • limiting hazardous energy (e.g. by rupture disks, temperature controllers, safety valves, rated break points); • using suitable construction and other materials (e.g. solid, sufficiently resistant against corrosion and ageing, glare-free, break-proof, non-toxic, non-inflammable, non-combustible, non-sliding); • designing equipment in accordance with its function, material, load, and ergonomics principles; • using fail-safe control devices employing technical means; • employing technical means of informing (e.g. danger signal); • protective equipment for separating, attaching, rejecting, catching, etc.; • suction equipment, exhaust hoods, when needed; • protection and emergency rooms; and • couplings or locks. technical measures refer to, e.g., • physical, chemical or biological processes; • energy, material and information flow in connection with the applied processes; • properties of materials and changes in the properties; and • function and design of technical products, parts and connections. the iterative (repeated) risk reduction process can be concluded after achieving adequate risk reduction and, if applicable, a favourable outcome of risk comparison. adequate risk reduction can be considered to have been achieved when one is able to answer each of the following questions positively: • have all operating conditions and all intervention procedures been taken into account? • have hazards been eliminated or their risks been reduced to the lowest practicable level? • is it certain that the measures undertaken do not generate new hazards? • are the users sufficiently informed and warned about the residual risks? • is it certain that the operator's working conditions are not jeopardized by the protective measures taken? • are the protective measures compatible with each other? • has sufficient consideration been given to the consequences that can arise from the use of a machine designed for professional/industrial use when it is used in a non-professional/non-industrial context? • is it certain that the measures undertaken do not excessively reduce the ability of the machine to perform its intended function? there are still many potential risks connected with hazardous substances about which more information is needed. because the knowledge about the relation between their dose and mode of action is not sufficient for controlling such risks, more research is needed. the following list highlights the themes of the numerous questions related to such risks: • potentially harmful organisms; • toxicants, carcinogens; • pesticides, pollutants, poisonous substances; • genetically engineered substances; • relation between chemical and structural properties and toxicity; • chemical structure and chemical properties and the relation to reactivity and reaction possibilities of organic compounds to metabolic reaction and living systems; • modes of action, genotoxicity, carcinogenicity, effects on humans/animals; • potentially harmful organisms in feedstuffs and animal faeces; • viruses and pathogens; • bacteria in feedstuffs and faeces; • parasites in feedstuffs and animal faeces; • pests in stored feedstuffs; • probiotics as feed additives; and • preservatives in feedstuffs. violent actions damaging society, property or people have increased, and they seem to spread both internationally as well as within countries. these new risks are difficult to predict and manage, as the very strategy of the actors is to create unexpected chaotic events. certain possibilities to predict the potential types of hazards do exist, and comprehensive predictive analyses have been done (meyerson, reaser ) . new methodologies are needed to predict the risk of terrorist actions, and also the strategies for risk management need to be developed. due to the numerous background factors, the preparedness of societies against these risks needs to be strengthened. table . lists important societal systems which are vulnerable to acts of terrorism. the situation in the developing countries needs to be tackled with specific methods. one has to answer the following questions: • what specific examples of prevention instruments can be offered? • what are the prerequisites for success? • how can industrialized countries assist the developing countries in carrying out preventive actions? • how should priorities be set according to the available resources? one possibility is to start a first-step programme, the goal of which is higher productivity and better workplaces. it can be carried out by improving • storage and handling of materials: -provide storage racks for tools, materials, etc.; -put stores, racks etc. on wheels, whenever possible; -use carts, conveyers or other aids when moving heavy loads; -use jigs, clamps or other fixtures to hold items in place. • work sites: -keep the working area clear of everything that is not in frequent use. • machine safety: -install proper guards to dangerous tools/machines; -use safety devices; -maintain machines properly. • control of hazardous substances: -substitute hazardous chemicals with less hazardous substances; -make sure that all organic solvents, paints, glues, etc., are kept in covered containers; -install or improve local exhaust ventilation; -provide adequate protective goggles, face shields, earplugs, safety footwear, gloves, etc.; -instruct and train workers; -make sure that workers wash their hands before eating and drinking, and change their clothes before going home. • lighting: -make sure that lighting is adequate. • social and sanitary facilities: -provide a supply of cool, safe drinking water; -have the sanitary facilities cleaned regularly; -provide a hygienic place for meals; -provide storage for clothing or other belongings; -provide first aid equipment and train a qualified first-aider. • premises: -increase natural ventilation by having more roof and wall openings, windows or open doorways; -move sources of heat, noise, fumes, arc welding, etc., out of the workshop, or install exhaust ventilation, noise barriers, or other solutions; -provide fire extinguishers and train the workers to use them; -clear passageways, provide signs and markings. • work organization: -keep the workers alert and reduce fatigue through frequent changes in tasks, opportunities to change work postures, short breaks, etc.; -have buffer stocks of materials to keep work flow constant; -use quality circles to improve productivity and quality. risk combination of the probability of an event and its consequences. the term "risk" is generally used only when there is at least a possibility of negative consequences. in some situation, risk arises from the possibility of deviation from the expected outcome or event. outcome of an event or a situation, expressed in quality and in quantity. it may result in a loss or in an injury or may be linked to it. the result can be a disadvantage or a gain. in this case the event or the situation is the source. in connection with every analysis it has to be checked whether the cause is given empirically, or follows a set pattern, and whether there is scientific agreement regarding these circumstances. note there can be more than one consequence from one event. note consequences can range from positive to negative. the consequences are always negative from the viewpoint of safety. extent to which an event is likely to occur. note iso - : gives the mathematical definition of probability as "a real number in the interval to attached to a random event. it can be related to a long-run relative frequency of occurrence or to a degree of belief that an event will occur. for a high degree of belief the probability is near ". note frequency rather than probability may be used in describing risk. degrees of belief about probability can be chosen as classes or ranks such as: rare/unlikely/moderate/likely/almost certain, or incredible/improbable/ remote/occasional/probable/frequent. remark: informal language often confuses frequency and probability. this can lead to wrong conclusions in safety technology. probability is the degree of coincidence of the time frequency of coincidental realization of a fact from a certain possibility. coincidence is an event which basically can happen, may be cause-related, but does not occur necessarily or following a set pattern. it may also not occur (yes-or-no-alternative). data for probability of occurring with specific kinds of occurrence and weight of consequences can be: in a statistical sense: empirical, retrospective, real in a prognostic sense: speculative, prospective, probabilistic occurrence of a particular set of circumstances regarding place and time. an event can be the source of certain consequences (empirically to be expected with certain regularity). the event can be certain or uncertain. the event can be a single occurrence or a series of occurrences. the probability associated with the event can be estimated for a given period of time. task range by which the significance of risk is assessed. note risk criteria can include associated costs and benefits, legal and statutory requirements, socio-economic and environmental aspects, the concerns of stakeholders, priorities and other inputs to the assessment. the way in which a stakeholder views a risk based on a set of values or concerns. note risk perception depends on the stakeholder's needs, issues and knowledge. note risk perception can differ from objective data. exchange or sharing of information about risk between the decision-makers and other stakeholders. overall process of risk analysis and risk evaluation. systematic use of information to identify sources and to estimate the risk. note risk analysis provides a basis for risk evaluation, risk treatment, and risk acceptance. note information can include historical data, theoretical analyses, informal opinions, and the concerns of stakeholders. process used to assign figures, values to the probability and consequences of a risk. note risk estimation can consider cost, benefits, the concerns of stakeholders, and other variables, as appropriate for risk evaluation. process of comparing the estimated risk against given risk criteria to determine the significance of a risk. process of selection and implementation of measures to modify risk. note risk treatment measures can include avoiding, optimizing, transferring or retaining risk. actions implementing risk management decisions. note risk control may involve monitoring, re-evaluation, and compliance with decisions. process, related to a risk, to minimize the negative and to maximize the positive consequences (and their respective probabilities). actions taken to lessen the probability, negative consequences or both, associated with a risk. limitation of any negative consequences of a particular event. decision not to become involved in, or action to withdraw from, a risk situation. sharing with another party the burden of loss or benefit of gain, for a risk. note legal or statutory requirements can limit, prohibit or mandate the transfer of a certain risk. note risk transfer can be carried out through insurance or other agreements. note risk transfer can create new risks or modify existing ones. note relocation of the source is not risk transfer. acceptance of the burden of loss, or benefit of gain, from a particular risk. note risk retention includes the acceptance of risks that have not been identified. note risk retention does not include means involving insurance, or transfer in other ways. this includes risk assessment, risk treatment, risk acceptance and risk communication. risk assessment is risk analysis, with identification of sources and risk estimation, and risk evaluation. risk treatment includes avoiding, optimizing, transferring and retaining risk. → risk acceptance → risk communication harm physical injury or damage to the health of people or damage to property or the environment [iso/iec guide ]. note harm includes any disadvantage which is causally related to the infringement of the object of legal protection brought about by the harmful event. note in the individual safety-relevant definitions, harm to people, property and the environment may be included separately, in combination, or it may be excluded. this has to be stated in the respective scope. potential source of harm [iso/iec guide ]. the term "hazard" can be supplemented to define its origin or the nature of the possible harm, e.g., hazard of electric shock, crushing, cutting, dangerous substances, fire, drowning. in every-day informal language, there is insufficient differentiation between source of harm, hazardous situation, hazardous event and risk. circumstance in which people, property or the environment are exposed to one or more hazards [iso/iec guide ]. note circumstance can last for a shorter or longer period of time. event that can cause harm [din en ] . the hazardous event can be preceded by a latent hazardous situation or by a critical event. combination of the probability of occurrence of harm and the severity of that harm [iso/iec guide ]. note in many cases, only a uniform extent of harm (e.g. leading to death) is taken into account, or the occurrence of harm may be independent of the extent of harm, as in a lottery game. in these cases, it is easier to make a probability statement; risk assessment by risk comparison [din en ] thus becomes much simpler. note risks can be grouped in relation to different variables, e.g. to all people or only those affected by the incident, to different periods of time, or to performance. the probabilistic expectation value of the extent of harm is suitable for combining the two probability variables. note risks which arise as a consequence of continuous emission, e.g. noise, vibration, pollutants, are affected by the duration and level of exposure of those affected. risk which is accepted in a given context based on the current values of society [iso/iec guide ]. the acceptable risk has to be taken into account in this context, too. note safety-relevant definitions are oriented to the maximum tolerable risk. this is also referred to as limit risk. note tolerability is also based on the assumption that the intended use in addition to a reasonably predictable misuse of the products, processes and services, is complied with. freedom from unacceptable risk [iso/iec guide ]. note safety is indivisible. it cannot be split into classes or levels. note safety is achieved by risk reduction, so that the residual risk in no case exceeds the maximum tolerable risk. existence of an unacceptable risk. note safety and danger exclude one another -a technical product, process or service cannot be safe and dangerous at the same time. means used to reduce risk [iso/iec guide ]. note protective measures at the product level have priority over protective measures at the workplace level. preventive measure means assumed, but not proven, to reduce risk. risk remaining after safety measures have been taken [din en ] . note residual risk may be related to the use of technical products, processes and services. systematic use of available information to identify hazards and to estimate their risks [iso/iec guide ]. determination of connected risk elements of all hazards as a basis for risk assessment. decision based on the analysis of whether the tolerable risk has been exceeded [iso/iec guide ]. overall process of risk analysis and risk evaluation [iso/iec guide ]. use of a product, process or service in accordance with information provided by the supplier [iso/iec guide ]. note information provided by the supplier also includes descriptions issued for advertising purposes. use of a product, process or service in a way not intended by the supplier, but which may result from readily predictable human behaviour [iso/iec guide ]. safety-related formulation of contents of a normative document in the form of a declaration, instructions, recommendations or requirements [compare en , safety related]. the information set down in technical rules is normally restricted to certain technical relations and situations; in this context, it is presumed that the general safety-relevant principles are followed. a procedure with the aim to reduce risk of a (technical) product, process or service according to the following steps serves to reach the safety goals in the design stage: • safety-related layout; • protective measures; • safety-related information for users. function inevitable to maintain safety. a function which, in case of failure, allows the tolerable risk to be immediately exceeded. depending on the situation, it is possible to use one method or a combination of several methods. intuitive hazard detection spontaneous, uncritical listing of possible hazards as a result of brainstorming by experts. group work which is as creative as possible. writing ideas down (on a flip chart) first, then evaluating them. technical documentation (instructions, requirements) is available for many industrial plant and work processes, describing the hazards and safety measures. this documentation has to be obtained before continuing with the risk analysis. the deviations between the set point and the actual situation of individual components are examined. information on the probability of failure of these elements may be found in technical literature. examining the safety aspects in unusual situations (emergency, repair, starting and stopping) when plans are made to modify the plant or processes. a systematic check of the processes and plant parts for effects in normal operation and in case of set point deviations, using selected question words (and -or -not -too much -too little?). this is used in particular for measurement, control units, programming of computer controls, robots. all possible causes and combinations of causes are identified for an unwanted operating state or an event, and represented in the graphic format of a tree. the probability of occurrence of an event can be estimated from the context. the fault tree analysis can also be used retrospectively to clarify the causes of events. additional methods may be: human reliability analysis a frequency analysis technique which deals with the behaviour of human beings affecting the performance of the system, and estimates the influence of human error on reliability. a hazard identification and frequency analysis technique which can be used at an early stage in the design phase to identify and critically evaluate hazards. operating safety block program a frequency analysis technique which utilizes a model of the system and its redundancies to evaluate the operating safety of the entire system. classifying risks into categories, to establish the main risk groups. all typical hazardous substances and/or possible accident sources which have to be taken into account are listed. the checklist may be used to evaluate the conformity with codes and standards. this method is used to estimate whether coincidental failures of an entire series of different parts or modules within a system are possible and what the probable effects would be. estimate the influence of an event on humans, property or the environment. simplified analytical approaches, as well as complex computer models can be used. a large circle of experts is questioned in several steps; the result of the previous step together with additional information is communicated to all participants. during the third or fourth step the anonymous questioning concentrates on aspects on which no agreement is reached so far. basically this technique is used for making predictions, but is also used for the development of new ideas. this method is particularly efficient due to its limitation to experts. a hazard identification and evaluation technique used to establish a ranking of the different system options and to identify the less hazardous options. a frequency analysis technique in which a model of the system is used to evaluate variations of the input conditions and assumptions. a means to estimate and list risk groups; reviews risk pairs and evaluates only one risk pair at a time. overview of data from the past a technique used to identify possible problem areas; can also be used for frequency analysis, based on accident and operation safety data, etc. a method to identify latent risks which can cause unforeseeable incidents. cssr differs from the other methods in that it is not conducted by a team, and can be conducted by a single person. the overview points out essential safety and health requirements related to a machine and simultaneously to all relevant (national, european, international) standards. this information ensures that the design of the machine complies with the issued "state of the art" for that particular type of machine. the "what-if" method is an inductive procedure. the design and operation of the machine in question are examined for fairly simple applications. at every step "what-if" questions are asked and answered to evaluate the effect of a failure of the machine elements or of process faults in view of the hazards caused by the machine. for more complex applications, the "what-if" method is most useful with the aid of a "checklist" and the corresponding work division to allocate specific features of the process to persons who have the greatest experience and practice in evaluating the respective feature. the operator's behaviour and professional knowledge are assessed. the suitability of the equipment and design of the machine, its control unit and protective devices are evaluated. the influence of the materials processed is examined, and the operating and maintenance records are checked. the checklist evaluation of the machine generally precedes the more detailed methods described below. fmea is an inductive method for evaluating the frequency and consequences of component failure. when operating procedures or operator errors are investigated, then other methods may be more suitable. fmea can be more time-consuming than the fault tree analysis, because every mode of failure is considered for every component. some failures have a very low probability of occurrence. if these failures are not analyzed in depth this decision should be recorded in the documentation. the method is specified in iec "analysis techniques for system reliability -procedure for failure mode and effects analysis (fmea)". in this inductive method, the test procedures are based on two criteria: technology and complexity of the control system. mainly, the following methods are applicable: • practical tests of the actual circuit and fault simulation on certain components, particularly in suspected areas of performance identified during the theoretical check and analysis. • simulation of control behaviour (e.g. by means of hardware and/or software models). whenever complex safety-related parts of control systems are tested, it may be necessary to divide the system into several functional sub-systems, and to exclusively submit the interface to fault simulation tests. this technique can also be applied to other parts of machinery. mosar is a complete approach in steps. the system to be analyzed (machinery, process, installation, etc.) is examined as a number of sub-systems which interact. a table is used to identify hazards and hazardous situations and events. the adequacy of the safety measures is studied with a second table, and a third table is used to look at their interdependency. a study, using known tools (e.g. fmea) underlines the possible dangerous failures. this leads to the elaboration of accident scenarios. by consensus, the scenarios are sorted in a severity table. a further table, again by consensus, links the severity with the targets of the safety measures, and specifies the performance levels of the technical and organizational measures. the safety measures are then incorporated into the logic trees and the residual risks are analyzed via an acceptability table defined by consensus. ilo ( ) , , , , , the risks to health at work are numerous and originate from several sources. their origins vary greatly and they cause vast numbers of diseases, injuries and other adverse conditions, such as symptoms of overexertion or overload. traditional occupational health risk factors and their approximate numbers are given in table . . the exposure of workers to hazards or other adverse conditions of work may lead to health problems, manifested in the workers' physical health, psysical workload, psychological disturbances or social aspects of life. workers may be exposed to various factors alone or in different types of combinations, which may or may not show interaction. the assessment of interacting risk factors is complex and may lead to substantial differences in the final risk estimates when compared with estimates of solitary factors. examples of interaction between different risk factors in the work environment are given in table . . the who estimate of the total number of occupational diseases among the billion workers of the world is million a year. this is likely to be an under-estimate due to the lack of diagnostic services, limited legislative coverage of both workers and diseases, and variation in diagnostic criteria between different parts of the world. the mortality from occupational diseases is substantial, comparable with other major diseases of the world population such as malaria or tuberculosis. the recent ilo estimate discloses . million deaths a year from work-related causes in the world including deaths from accidents, dangerous substances, and occupational diseases. eightyfive percent ( %) of these deaths take place in developing countries, where the diagnostic services, social security to families and compensation to workers are less developed. although the risk is decreasing in the industrialized world, the trend is increasing in the rapidly industrializing and transitory countries. a single hazard alone, such as asbestos exposure, is calculated to cause , cancers a year with a fatal outcome in less than two years after diagnosis (takala ). the incidence rates of occupational diseases in well registered industrialized countries are at the level of - cases/ , active employees/year, i.e., the incidence levels are comparable with major public health problems, such as cardiovascular diseases, respiratory disorders, etc. in the industrialized countries, the rate of morbidity from traditional occupational diseases, such as chemical poisonings, is declining, while musculoskeletal and allergic diseases are on the increase. about biological factors that are hazardous to workers' health have been identified in various work environments. some of the new diseases recognized are blood-borne infections, such as hepatitis c and hiv, and exotic bacterial or viral infections transmitted by increasing mobility, international travelling and migration of working people. also some hospital infections and, e.g., drug-resistant tuberculosis, are being contracted increasingly by health care personnel. in the developing countries the morbidity picture of occupational diseases is much less clear for several reasons: low recognition rates, rotation and turnover of workers, shorter life expectancy which hides morbidity with a long latency period, and the work-relatedness of several common epidemic diseases, such as malaria and hiv/aids (rantanen ). the estimation of so-called work-related diseases is even more difficult than that of occupational diseases. they may be about -fold more prevalent than the definite occupational diseases. several studies suggest that siegfried radandt, jorma rantanen and ortwin renn work-related allergies, musculoskeletal disorders and stress disorders are showing a growing trend at the moment. the prevention of work-related diseases is important in view of maintaining work ability and reducing economic loss from absenteeism and premature retirement. the proportion of work-relatedness out of the total morbidity figures has been estimated and found surprisingly high (nurminen and karjalainen , who ) (see table . ). the public health impact of work-related diseases is great, due to their high prevalence in the population. musculoskeletal disorders are among the three most common chronic diseases in every country, which implies that the attribution of work is very high. similarly, cardiovascular diseases in most industrialized countries contribute to % of the total mortality. even a small attributable fraction of work-relatedness implies high rates of morbidity and mortality related to work. the concept of disease is in general not a simple one. when discussing morbidity one has to recognize three different concepts: . illness = an individual's perception of a health problem resulting from either external or internal causes. . disease = an adverse health condition diagnosed by a doctor or other health professional. . sickness = a socially recognized disease which is related to, for example, social security actions or prescription of sick leave, etc. when dealing with occupational and work-related morbidity, one may need to consider any of the above three aspects of morbidity. a recognized occupational disease, however, belongs to group , i.e. it is a sickness defined by legal criteria. medical evidence is required to show that the condition meets the criteria of an occupational disease before recognition can be made. there are dozens of definitions for occupational disease. the content of the concept varies, depending on the context: a) the medical concept of occupational disease is based on a biomedical or other health-related etiological relationship between work and health, and is used in occupational health practice and clinical occupational medicine. b) the legal concept of occupational disease defines the disease or conditions which are legally recognized as conditions caused by work, and which lead to liabilities for recognition, compensation and often also prevention. the legal concept of occupational disease has a different background in different countries, often declared in the form of an official list of occupational diseases. there is universal discrepancy between the legal and medical concept, so that in nearly all countries the official list of recognized occupational diseases is shorter than the medically established list. this automatically implies that a substantial proportion of medically established occupational diseases remain unrecognized, unregistered, and consequently also uncompensated. the definition of occupational disease, as used in this chapter, summarizes various statements generated during the history of occupational medicine: an occupational disease is any disease contracted as a result of exposures at work or other conditions of work. the general criteria for the diagnosis and recognition of an occupational disease are derived from the core statements of various definitions: . evidence on exposure(s) or condition(s) in work or the work environment, which on the basis of scientific knowledge is (are) able to generate disease or some other adverse health condition. . evidence of symptoms and clinical findings which on the basis of scientific knowledge can be associated with the exposure(s) or condition(s) in concern. . exclusion of non-occupational factors or conditions as a main cause of the disease or adverse health condition. point often creates problems, as several occupationally generated clinical conditions can be caused also by non-occupational factors. on the other hand, several factors from different sources and environments are involved in virtually every disease. therefore the wordings "main cause" or "principal cause" are used. the practical solution in many countries is that the attribution of work needs to be more than %. usually the necessary generalizeable scientific evidence is obtained from epidemiological studies, but also other types of evidence, e.g. well documented clinical experience combined with information on working conditions may be acceptable. in some countries, like finland, any disease of the worker which meets the above criteria can be recognized as an occupational disease. in most other countries, however, there are official lists of occupational diseases which determine the conditions and criteria on which the disease is considered to be of occupational origin. in who launched a new concept: work-related disease (who ) . the concept is wider than that of an occupational disease. it includes: a) diseases in which the work or working conditions constitute the principal causal factor. b) diseases for which the occupational factor may be one of several causal agents, or the occupational factor may trigger, aggravate or worsen the disease. c) diseases for which the risk may be increased by work or work-determined lifestyles. the diseases in category (a) are typically recognized as legally determined occupational diseases. categories (b) and (c) are important regarding the morbidity of working populations, and they are often considered as important targets for prevention. in general, categories (b) and (c) cover greater numbers of people, as the diseases in question are often common noncommunicable diseases of the population, such as cardiovascular diseases, musculoskeletal disorders, and allergies and, to a growing extent, stressrelated disorders (see table . ). the concept of work-related disease is very important from the viewpoint of occupational health risk assessment and the use of its results for preventive purposes and for promoting health and safety at work. this is because preventive actions in occupational health practice cannot be limited only to legally recognized morbidity. the lists of occupational diseases contain great numbers of agents that show evidence on occupational morbidity. according to the ilo recommendation r ( ): list of occupational diseases, the occupational diseases are divided into four main categories: . diseases resulting from single causes following the categories listed in table . . the most common categories are physical factors, chemical agents, biological factors and physical work, including repetitive tasks, poor ergonomic conditions, and static and dynamic work. . diseases of the various organs: respiratory system, nervous system, sensory organs, internal organs, particularly liver and kidneys, musculoskeletal system, and the skin. . occupational cancers. . diseases caused by other conditions of work. research on risk perception shows differences in how different types of risks are viewed. instant, visible, dramatic risk events, particularly ones that cause numerous fatalities or severe visible injuries in a single event generally arouse much attention, and are given high priority. on the other hand, even great numbers of smaller events, such as fatal accidents of single workers, arouse less attention in both the media and among regulators, even though the total number of single fatal accidents in a year may exceed the number of fatalities in major events by several orders of magnitude. occupational diseases, with the exception of a few acute cases, are silent, develop slowly, and concern only one or a few individuals at a time. furthermore, the diseases take months or years to develop, in extreme cases even decades, after the exposure or as a consequence of accumulation of exposure during several years. as occupational health problems are difficult to detect and seriously under-diagnosed and under-reported, they tend to be given less priority than accidents. the perception of occupational disease risk remains low in spite of their severity and relatively high incidence. particularly in industrialized countries, the extent of occupational health problems is substantially greater than that of occupational accidents. on a global scale, the estimated number of fatalities due to occupational accidents is , and the respective estimate for fatalities due to work-related diseases is . million a year, giving a fatal accident/fatal disease ratio of to . the corresponding ratio in the eu- is to (takala ). the risk distribution of ods is principally determined by the nature of the work in question and the characteristics of the work environment. there is great variation in the risk of ods between the lowest and highest risk occupations. in the finnish workforce, the risk between the highest risk and the lowest risk occupations varies by a factor of . the highest risk occupations carry a risk which is - times higher than the average for all occupations. the risk of an occupational disease can be estimated on the basis of epidemiological studies, if they do exist in the case of the condition in question. on the other hand, various types of economic activity, work and occupations carry different types of risks, and each activity may have its own risk profile. by examining the available epidemiological evidence, we can recognize high-risk occupations and characterize the typical risks connected with them ( figure . , table . ). as an example, the risk of occupational asthma, dermatosis or musculoskeletal disorders is common in several occupations, but not in all. there may be huge differences in risks between different occupations. the occupations carrying the highest risk for occupational asthma, occupational skin diseases and work-related tenosynovitis, in - , are shown in table . . assessment of the risk of occupational diseases has an impact on research priorities. table . shows the priorities for research in four countries. the similarity of the priorities is striking, revealing that the problems related to the risks of occupational diseases are universal. the diagnosis of occupational diseases is important for the treatment of the disease, and for prevention, registration and compensation. the diagnosis is based on information obtained from: a) data on the work and the work environment usually provided by the employer, occupational health services, occupational safety committee, or expert bodies carrying out hygienic and other services for the workplace. b) information on the health examination of individual workers. the authorities in many countries have stipulated legal obligations for high-risk sectors to follow up the workers' health and promote early detection of changes in their health. occupational health services keep records on examinations. c) workers with special symptoms (for example, asthmatic reactions) are taken into the diagnostic process as early as possible. epidemiological evidence is a critical prerequisite for recognizing causal relationship between work and disease. epidemiology is dependent on three basic sources of information on work and the work environment: (a) exposure assessment that helps to define the "dose" of risk factor at work, (b) the outcome assumed to occur as a biological (or psychological) response to the exposures involved, and (c) time, which has a complex role in various aspects of epidemiology. all these sources are affected by the current dynamics of work life which has major impact on epidemiological research and its results. exposure assessment is the critical initial step in risk assessment. as discussed in this chapter, accurate exposure assessment will become more difficult and cumbersome than before in spite of remarkable achievements in measurement, analysis and monitoring methods in occupational hygiene, toxicology and ergonomics. great variations in working hours and individu-alization of exposures, growing fragmentation and mobility increase the uncertainties, which are multiplied. structural uncertainty, measurement uncertainty, modelling uncertainty, input data uncertainty and natural uncertainty amplify each other. as a rule, variation in any direction in exposure assessment tends to lead to underestimation of risk, and this has severe consequences to health. personal monitoring of exposures, considering variations in individual doses, and monitoring internal doses using biological monitoring methods help in the control of such variation. a monofactorial exposure situation in the past was ideal in the assessment because of its manageability. it also occurs usually as a constant determinant for long periods of time and can be regularly and continuously measured and monitored. this is very seldom the case today, and exposure assessment in modern work life is affected by discontinuities of the enterprise, of technologies and production methods, and turnover of the workforce, as well as the growing mobility and internationalization of both work and workers. company files that were earlier an important source of exposure and health data no longer necessarily fulfil that function. in addition, the standard -h time-weighted average for exposure assessment can no longer be taken as a standard, as working hours are becoming extremely heterogeneous. assessment of accurate exposure is thus more and more complex and cumbersome, and new strategies and methods for the quantification of exposure are needed. three challenges in particular can be recognized: a) the challenge arising from numerous discontinuities, fragmentation and changes in the company, employment and technology. although in the past company data were collected from all sources that were available, collective workroom measurements were the most valuable source of data. due to the high mobility of workers and variation in the work tasks, personal exposure monitoring is needed that follows the worker wherever he or she works. special smart cards for recording all personal exposures over years have been proposed, but so far no system-wide action has been possible. in radiation protection, however, such a personal monitoring system has long been a routine procedure. b) the complex nature of exposures where dozens of different factors may be involved (such as those in indoor air problems) and acting in combinations. table . gives a list of exposing factors in modern work life, many of which are difficult to monitor. c) new, rapidly spreading and often unexpected exposures that are not well characterized. often their mechanisms of action are not known, or the fast spread of problems calls for urgent action, as in the case of bovine spongiform encephalopathy (bse) in the s, sars outbreak in , and in the new epidemics of psychological stress or musculoskeletal disorders in modern manufacturing. the causes of occupational diseases are grouped into several categories by the type of factor (see table . ). a typical grouping is the one used in ilo recommendation no. . the lists of occupational diseases contain diseases caused by one single factor only, but also diseases which may have been caused by multifactorial exposures. exposure assessment is a crucial step in the overall risk assessment. the growing complexity of exposure situations has led to the development of new methods for assessing such complex exposure situations. these methods are based on construction of model matrices for jobs which have been studied thoroughly for their typical exposures. the exposure profiles are illustrated in job exposure matrices (jem) which are available for dozens of occupations (heikkilä et al. , guo . several factors can cause occupational diseases. the jem is a tool used to convert information on job titles into information on occupational risk factors. jem-based analysis is economical, systematic, and often the only reasonable choice in large retrospective studies in which exposure assessment at the individual level is not feasible. but the matrices can also be used in the practical work for getting information on typical exposure profiles of various jobs. the finnish national job-exposure matrix (finjem) is the first and so far the only general jem that is able to give a quantitative estimation of cumulative exposure. for example, finjem estimates were used for exposure profiling on chemical exposures and several other cancer-risk factors for occupational categories. the jem analysis has been further developed into task specific exposure matrices charting the exposure panorama of various tasks (benke et al. (benke et al. , . as the previous mono-causal, mono-mechanism, mono-outcome setting has shifted in the direction of multicausality, multiple mechanisms and multioutcomes, the assessment of risks has become more complex. some outcomes, as mentioned above, are difficult to define and measure with objective methods and some of them may be difficult to recognize by exposed groups themselves, or even by experts and researchers. for example, the objective measurement of stress reactions is still imprecise in spite of improvements in the analysis of some indicator hormones, such as adrenalin, noradrenalin, cortisol, prolactin, or in physical measurements, such as galvanic skin resistance and heart rate variability. questionnaires monitoring perceived stress symptoms are still the most common method for measuring stress outcomes. thanks to well organized registries, particularly in germany and the nordic countries, data on many of the relevant outcomes of exposure, such as cancer, pneumoconiosis, reproductive health disturbances and cardiovascular diseases can be accumulated, and long-term follow-up of outcomes at the group level is therefore possible. on the other hand, several common diseases, such as cardiovascular diseases, may have a work-related aetiology, but it may be difficult to show at individual level. the long-term data show that due to changes in the structure of economies, types of employment, occupational structures and conditions of work, many of the traditional occupational diseases, such as pneumoconiosis and acute intoxications have almost disappeared. several new outcomes have appeared, however, such as symptoms of physical or psychological overload, psychological stress, problems of adapting to a high pace of work, and uncertainty related to rapid organizational changes and risk of unemployment. in addition, age-related and work-related diseases among the ageing workforce are on the increase (kivimäki et al. , ilmarinen . these new outcomes may have a somatic, psychosomatic or psychosocial phenotype, and they often appear in the form of symptoms or groups of symptoms instead of well-defined diagnoses. practising physicians or clinics are not able to set an icd (international statistical classification of diseases and health-related conditions)-coded diagnosis for them. in spite of their diffuse nature, they are still problems for both the worker and the enterprise, and their consequences may be seen as sickness absenteeism, premature retirement, loss of job satisfaction, or lowered productivity. thus, they may have even a greater impact on the quality of work life and the economy than on clinical health. many such outcomes have been investigated by using questionnaire surveys among either representative samples of the whole workforce or by focusing the survey on a specific sector or occupational group. the combination of data from the surveys of "exposing factors", such as organizational changes, with questionnaire surveys of "outcomes", such as sickness absenteeism, provides epidemiological information on the association between the new exposures and the new outcomes. there are, however, major problems in both the accurate measurement of the exposures and outcomes, and also, the information available on the mechanisms of action is very scarce. epidemiology has expanded the focus of our observations from crosssectional descriptions to longitudinal perspectives, by focussing attention on the occurrence of diseases and finding associations between exposure and morbidity. such an extension of vision is both horizontal and vertical, looking at the causes of diseases. time is not only a temporal parameter in epidemiology, but has also been used for the quantification of exposure, measurement of latencies, and the detection of acceleration or slowing of the course of biological processes. as the time dimension in epidemiology is very important, the changes in temporal parameters of the new work life also affect the methods of epidemiological research. the time dimension is affected in several ways. first, the fragmentation and discontinuities of employment contracts, as described above, break the accumulation of exposure time into smaller fragments, and continuities are thus difficult to maintain. collecting data on cumulative exposures over time becomes more difficult. the time needed for exposure factors to cause an effect becomes more complex, as the discontinuities typical to modern work life allow time for biological repair and elimination processes, thus diluting the risk which would get manifested from continuous exposure. the dosage patterns become more pulse-type, rather than being continuous, stable level exposures. this may affect the multi-staged mechanisms of action in several biological processes. the breaking up of time also increases the likelihood of memory bias of respondents in questionnaire studies among exposed workers, and thus affects the estimation of total exposures. probably the most intensive effect, however, will be seen as a consequence of the variation in working hours. for example, instead of regular work of hours per day, hours per week and months per year, new time schedules and total time budgets are introduced for the majority of workers in the industrial society. the present distribution of weekly working hours in finland is less than hours per week for one third of workers, regular - hours per week for one third, and - hours per week for the remaining third. thus the real exposure times may vary substantially even among workers in the same jobs and same occupations, depending on the working hours and the employment contract (temporary, seasonal, part-time, full-time) (härmä , piirainen et al. . such variation in time distribution in "new work life" has numerous consequences for epidemiological studies, which in the past "industrial society" effectively utilized the constant time patterns at work for the assessment of exposures and outcomes and their interdependencies. the time dimension also has new structural aspects. as biological processes are highly deterministic in terms of time, the rapid changes in work life cannot wait for the maturation of results in longitudinal follow-up studies. the data are needed rapidly in order to be useful in the management of working conditions. this calls for the development of rapid epidemiological methods which enable rapid collection of the data and the making of analyses in a very short time, in order to provide information on the effects of potential causal factors before the emergence of a new change. often these methods imply the compromising of accuracy and reliability for the benefit of timeliness and actuality. as occupational epidemiology is not only interested in acute and short-term events, but looks at the health of workers over a - -year perspective, the introduction of such new quick methods should not jeopardize the interest and efforts to carry out long-term studies. epidemiology has traditionally been a key tool in making a reliable risk assessment of the likelihood of the adverse outcomes from certain levels of exposure. the new developments in work life bring numerous new challenges to risk assessment. as discussed above, the new developments in work life have eliminated a number of possibilities for risk assessment which prevailed in the stable industrial society. on the other hand, several new methods and new information technologies provide new opportunities for collection and analysis of data. traditionally, the relationship between exposure and outcome has been judged on the basis of the classical criteria set by hill ( ) . höfler ( ) crystallizes the criteria with their explanations as the following: . strength of association: a strong association is more likely to have a causal component than is a modest association. . consistency: a relationship is observed repeatedly. . specificity: a factor influences specifically a particular outcome or population. . temporality: the factor must precede the outcome it is assumed to affect. ing dose of exposure or according to a function predicted by a substantive theory. . plausibility: the observed association can be plausibly explained by substantive matter (e.g. biological) explanations. . coherence: a causal conclusion should not fundamentally contradict present substantive knowledge. . experiment: causation is more likely if evidence is based on randomized experiments. . analogy: for analogous exposures and outcomes an effect has already been shown. the hill criteria have been subjected to scrutiny, and sven hernberg has analyzed them in detail from the viewpoint of occupational health epidemiology. virtually all the hill criteria are affected by the changes in the new work life, and therefore methodological development is now needed. a few comments on causal inference are made here in view of the critiques by rothman ( ), hernberg ( ) and höfler ( ) : the strength of association will be more difficult to demonstrate due to the growing fragmentation that tends to diminish the sample sizes. the structural change that removes workers from high-level exposures to lower and shorterterm exposures may dilute the strength of effect, which may still prevail, but at a lower level. consistency of evidence may also be affected by the higher variation in conditions of work, study groups, multicultural and multiethnic composition of the workforce, etc. similarly, in the multifactorial, multi-mechanism, multi-outcome setting, the specificity criterion is not always relevant. the temporal dimension has already been discussed. in rapidly changing work life the follow-up times before the next change and before turnover in the workforce may be too short. the outcomes may also be defined by the exposures that have taken place long ago but have not been considered in the study design because historical data are not available. the biological gradient may be possible to demonstrate in a relatively simple exposure-outcome relationship. however, the more complex and multifactorial the setting becomes, the more difficult it may be to show the doseresponse relationship. the dose-response relationship may also be difficult to demonstrate in the cases of relatively ill-defined outcomes which are difficult to measure, but which can be detected as qualitative changes. biological plausibility is an important criterion which in a multimechanism setting may at least in part be difficult to demonstrate. on the other hand, the mechanisms of numerous psychological and psychosocial outcomes lack explanations, even though they undoubtedly are work-related. the missing knowledge of the mechanism of action did not prevent the establishment of causality between asbestos and cancer in a pleural sack or a lung. as many of the new outcomes may be context-dependent, the coherence criterion may be irrelevant. similarly, many of the psychosocial outcomes are difficult to put into an experimental setting, and it can be difficult to make inferences based on analogy. all of the foregoing implies that the new dynamic trends in work life challenge epidemiology in a new way, particularly in the establishment of causality. knowledge of causality is required for the prevention and management of problems. the hill criteria nevertheless need to be supplemented with new ones to meet the conditions of the new work life. similarly, more definitive and specific criteria and indicators need to be developed for the new exposures and outcomes. many of the challenges faced in the struggle to improve health and safety in modern work life can only be solved with the help of research. research on occupational health in the rapidly changing work life is needed more than ever. epidemiology is, and will remain, a key producer of information needed for prevention policies and for ensuring healthy and safe working conditions. the role of epidemiology is, however, expanding from the analysis of the occurrence of well-defined clinical diseases to studies on the occurrence of several other types of exposure and outcome, and their increasingly complex associations. as the baseline in modern work life is shifting in a more dynamic direction, and many parameters in work and the workers' situation are becoming more fragmented, incontinuous and complex, new approaches are needed to tackle the uncertainties in exposure assessment. the rapid pace of change in work life calls for the development of assessment methods to provide up-todate data quickly, so that they can be used to manage these changes and their consequences. many new outcomes which are not possible to register as clinical icd diagnoses constitute problems for today's work life. this is particularly true in the case of psychological, psychosocial and many musculoskeletal outcomes which need to be managed by occupational health physicians. methods for the identification and measurement of such outcomes need to be improved. the traditional hill criteria for causal inference are not always met even in cases where true association does exist. new criteria suitable for a new situation should be established without jeopardizing the original objective of ascertaining the true association. developing the bayesian inference further through utilization of a priori knowledge and a holistic approach may provide responses to new challenges. new neural network softwares may help in the management of the growing complexity. the glory of science does not lie in the perfection of a scientific method but rather in the recognition of its limitations. we must keep in mind the old saying: "absence of evidence is not evidence of absence". instead, it is merely a consequence of our ignorance that should be reduced through further efforts in systematic research, and particularly through epidemiology. and secondly, the ultimate value of occupational health research will be determined on the basis of its impact on practice in the improvement of the working conditions, safety and health of working people. changing conditions of work, new technologies, new substances, new work organizations and working practices are associated with new morbidity patterns and even with new occupational and work-related diseases. the new risk factors, such as rapidly transforming microbials and certain social and behavioural "exposures" may follow totally new dynamics when compared with the traditional industrial exposures (self-replicating nature of microbials and spreading of certain behaviours, such as terrorism) (smolinski et al. , loza . several social conditions, such as massive rural-urban migration, increased international mobility of working people, new work organizations and mobile work may cause totally new types of morbidity. examples of such development are, among others, the following: • mobile transboundary transportation work leading to the spread of hiv/aids. • increased risk of metabolic syndrome, diabetes and cardiovascular diseases aggravated by unconventional working hours. • increased risk of psychological burnout in jobs with a high level of longterm stress. • virtually a global epidemic of musculoskeletal disorders among vdu workers with high work load, psychological stress and poor ergonomics. the incidences of occupational diseases may not decline in the future, but the type of morbidity may change. the direction of trend in industrialized countries is the prominence of work-related morbidity and new diseases, while the traditional occupational diseases such as noise injury, pneumoconiosis, repetitive strain and chemical intoxications may continue to be prevalent in developing countries for long periods in the future. the new ergonomics problems are related to light physical work with a considerable proportion of static and repetitive workload. recent research points to an interesting interaction between unergonomic working conditions and psychological stress, leading to a combined risk of musculoskeletal disorders of the neck, shoulders and upper arms, including carpal tunnel syndrome in the wrist. the muscle tension in static work is amplified by the uncontrolled muscular tension caused by psychological stress. furthermore, there seems to be wide inter-individual variation in the tendency to respond with spasm, particularly in the trapezius muscle of neck, under psychological stress. about % of the health complaints of working-aged people are related to musculoskeletal disorders, of which a substantial part is work-related. the epidemics have been resistant against preventive measures. new regulatory and management strategies may be needed for effective prevention and control measures (westgaard et al. , paoli and merllié ) . the st century will be the era of the brain at work and consequently of psychological stress. between % and % of eu workers in certain occupations report psychological stress due to high time pressure at work (parent-thirion et al. ). the occurrence of work-related stress is most prevalent in occupations with tight deadlines, pressure from clients, or the high level of responsibility for productivity and quality given to the workers. undoubtedly, the threat of unemployment increases the perception of stress as well. as a consequence, for example, in finland some % of workers report symptoms of psychological overload and about % show clinical signs of burn out. these are not the problems of low-paid manual workers only, but also, for example, highly educated and well-paid computer super-experts have an elevated risk of burnout as a consequence of often self-committed workload (kalimo and toppinen ) . unconventional and ever longer working hours are causing similar problems. for example, one third of finns work over hours a week, and of these % work over hours, and % often work - hours per week. it is important to have flexibility in the work time schedules, but it is counterproductive if the biologically determined physiological time rhythms of the worker are seriously offended. over % have a sleep deficit of at least one hour each day, and % are tired and somnolent at work (härmä et al. ) . the toughening global competition, growing productivity demands and continuous changes of work, together with job insecurity, are associated with increased stress. up to - % of workers in different countries and different sectors of the economy report high time pressure and tight deadlines. this prevents them from doing their job as well as they would like to, and causes psychological stress. psychological stress is particularly likely to occur if the high demands are associated with a low degree of self-regulation by the workers (houtman ) . stress, if continuous, has been found to be detrimental to physical health (cardiovascular diseases), mental health (psychological burnout), safety (accident risks), and musculoskeletal disorders (particularly hand-arm and shoulder-neck disorders). it also has a negative impact on productivity, sickness absenteeism, and the quality of products and services. the resulting economic losses due to sickness absenteeism, work disability and lower quality of products and services are substantial. the prevention of stress consists not only of actions targeted at the individual worker. there is also a need for measures directed at the work organization, moderation of the total workload, competence building and collaboration within the workplace (theorell ). the support from foremen and supervisors is of crucial importance in stress management programmes. another type of psychological burden is the stress arising from the threat of physical violence or aggressive behaviour from the part of clients. in finland some % of workers have been subjected to insults or the threat of physical violence, % have experienced sexual harassment, and % mental violence or bullying at work. the risk is substantially higher for female workers than for men. stress has been found to be associated with somatic health, cardiovascular diseases, mental disorders and depression. one of the new and partly re-emerging challenges of occupational health services is associated with the new trends in microbial hazards. there are several reasons for these developments, for instance, the generation of new microbial strains, structural changes in human habitations with high population densities, growing international travel, and changes possibly in our microbiological environment as a consequence of global warming. of the to million species in the world, about million are microbes. the vast majority of them are not pathogenic to man, and we live in harmony and symbiosis with many of them. we also use bacteria in numerous ways to produce food, medicines, proteins, etc. the pathogenic bacteria have been well controlled in the th century; this control had an enormous positive impact on human health, including occupational health. but now the microbial world is challenging us in many ways. new or re-emerging biological hazards are possible due to the transformation of viruses, the increased resistance of some microbial strains (e.g. tuberculosis and some other bacterial agents) and the rapid spread of contaminants through extensive overseas travelling (smolinski et al. ) . the scenarios of health hazards from the use of genetically manipulated organisms have not been realized, but biotechnological products have brought along new risks of allergies. a major indoor air problem is caused by fungi, moulds and chemical emissions from contaminated construction materials. new allergies are encountered as a consequence of the increasingly allergic constitution of the population and of the introduction of new allergens into the work environment. health care personnel are increasingly exposed to new microbial hazards due to the growing mobility of people. evidence of high rates of hepatitis b antigen positivity has been shown among health care workers who are in contact with migrants from endemic areas. along with the growing international interactions and mobility, a number of viral and re-emerging bacterial infections also affect the health of people engaged in health care and the care of the elderly, as well as personnel in migrant and refugee services, in social services and other public services. this section applies the general framework for risk governance (chapter ) to the area of environmental risks. why should we include this topic in a book that is dominantly dealing with occupational health risks and safety issues? there are two major reasons for this decision: . most risks that impact health and safety of human beings are also affecting the natural environment. it is therefore necessary for risk managers to reflect the consequences of risk-taking activities with respect to workers, the public and the environment. these risk consequences are all interconnected. our approach to foster an integral approach to risk and risk management requires the integration of all risk consequences. . environmental risks are characterized by many features and properties that highlight exemplary issues for many generic risk assessment and management questions and challenges. for example, the question of how to balance benefits and risks becomes more accentuated, if not human life, but damage to environmental quality is at stake. while most people agree that saving human lives takes priority over economic benefits, it remains an open question of how much environmental change and potential damage one is willing to trade off against certain economic benefits. this section is divided into two major parts. part will introduce the essentials of environmental ethics and the application of ethical principles to judging the acceptability of human interventions into the environment. part addresses the procedures for an analytic-deliberative process of decision making when using the risk governance framework developed in chapter . it should be noted that this section draws from material that the author has compiled for the german scientific council for global environmental change and that has been partially published in german in a special report of the council (wbgu ). the last section on decision making has borrowed material from an unpublished background document on decision making and risk management that dr. warner north and the author had prepared for the us national academy of sciences. should people be allowed to do everything that they are capable of doing? this question is posed in connection with new technologies, such as nanotubes, or with human interventions in nature, such as the clearance of primaeval forests so that the land can be used for agriculture. intuitively everyone answers this question with a definitive "no": no way should people be allowed to everything that they are capable of doing. this also applies to everyday actions. many options in daily life, from lying to minor deception, from breaking a promise up to going behind a friend's back, are obviously actions that are seen by all well-intentioned observers as unacceptable. however, it is much more difficult to assess those actions where the valuation is not so obvious. is it justified to break a promise when keeping the promise could harm many other people? actions where there are conflicts between positive and negative consequences or where a judgement could be made one way or the other with equally good justification are especially common in risk management. there is hardly anyone who wilfully and without reason pollutes the environment, releases toxic pollutants or damages the health of individuals. people who pursue their own selfish goals on the cost and risk of others are obviously acting wrongly and every legislator will sanction this behaviour with the threat of punishment or a penalty. but there is a need for clarification where people bring about a benefit to society with the best intentions and for plausible reasons and, in the process, risk negative impacts on others. in ethics we talk about "conflicting values" here. most decisions involving risks to oneself or others are made for some reason: the actors who make such interventions want to secure goods or services to consumers, for example, to ensure long-term jobs and adequate incomes, to use natural resources for products and services or to use nature for recycling waste materials from production and consumption that are no longer needed. none of this is done for reasons of brotherly love, but to maintain social interests. even improving one's own financial resource is not immoral mere for this reason. the list of human activities that pose risks onto others perpetrated for existential or economic reasons could be carried on into infinity. human existence is bound to taking opportunities and risks. here are just a few figures: around , years ago about million people lived on the earth. under the production conditions those days (hunter-gatherer culture) this population level was the limit for the human species within the framework of an economic form that only interfered slightly with man's natural environment. the neolithic revolution brought a dramatic change: the carrying capacity of the world for human beings increased by a factor of and more. this agrarian pre-industrial cultural form was characterized by tightly limited carrying capacity, in around the earth was capable of feeding approx. million people. today the world supports billion people -and this figure is rising. the carrying capacity in comparison to the neolithic age has thus increased thousand-fold and continues to grow in parallel to new changes in production conditions (fritsch ; kesselring ; mohr ) . the five "promethean innovations" are behind this tremendous achievement of human culture: mastering fire, using the natural environment for agriculture, transforming fossil fuels into thermal and mechanical energy, industrial production and substituting material with information (renn ) . with today's settlement densities and the predominantly industrial way of life, the human race is therefore dependent on the technical remodelling of nature. without doubt, it needs this for survival, especially for the well-being of the innumerable people, goods and services that reduce the stock of natural resources. with regard to the question of the responsibility of human interventions in nature, the question cannot be about "whether" but -even better -about "how much", because it is an anthropological necessity to adapt and shape existing nature to human needs. for example, the philosopher klaus michael meyer-abich sees the situation as follows: ". . . we humans are not there to leave the world as though we had never been there. as with all other life forms, it is also part of our nature and our lives to bring about changes in the world. of course, this does not legitimise the destructive ways of life that we have fallen into. but only when we basically approve of the changes in the world can we turn to the decisive question of which changes are appropriate for human existence and which are not" (meyer-abich ). therefore, to be able to make a sensible judgement of the balance between necessary interventions into the environment and the risks posed by these interventions to human health and environmental quality, the range of products and services created by the consumption of nature has to be considered in relation to the losses that are inflicted on the environment and nature. with this comparison, it can be seen that even serious interventions in nature and the environment did not occur without reflection, but to provide the growing number of people with goods and services; these people need them to survive or as a prerequisite for a "good" life. however, at the same time it must be kept in mind that these interventions often inflict irreversible damage on the environment and destroy possible future usage potentials for future generations. above and beyond this, for the human race, nature is a cradle of social, cultural, aesthetic and religious values, the infringement of which, in turn, has a major influence on people's well-being. on both sides of the equation, there are therefore important goods that have to be appreciated when interventions in nature occur. but what form should such an appreciation take? if the pros and cons of the intervention in nature have to be weighed against each other, criteria are needed that can be used as yardsticks. who can and may draw up such criteria, according to which standards should the interventions be assessed and how can the various evaluative options for action be compared with each other for each criterion? taking risks always involves two major components: an assessment of what we can expect from an intervention into the environment (be it the use of resources or the use of environments as a sink for our waste). this is the risk and benefit assessment side of the risk analysis. secondly, we need to decide whether the assessed consequences are desirable. whereas the estimate of consequences broadly falls in the domain of scientific research and expertise, with uncertainties and ambiguities in particular having to be taken into account (irgc , klinke and renn ) , the question about the foundations for evaluating various options for action and about drawing up standards guiding action is a central function of ethics (taylor ) . ethics can provide an answer to the question posed in the beginning ("should people be allowed to do everything that they are capable of doing?") in a consistent and transparent manner. in section . . , environmental ethics will be briefly introduced. this review is inspired by the need for a pragmatic and policy-oriented approach. it is not a replacement for a comprehensive and theoretically driven compendium of environmental ethics. environmental ethics will then be applied to evaluate environmental assets. in this process, a simple distinction is made between categorical principles -that must under no circumstances be exceeded or violated -and compensatory principles, where compensation with other competing principles is allowed. this distinction consequently leads to a classification of environmental values, which, in turn, can be broken down into criteria to appreciate options for designing environmental policies. in section . . , these ideas of valuation will be taken up and used to translate the value categories into risk handling guidelines. at the heart of the considerations here is the issue of how the aims of ethically founded considerations can be used to support and implement risk-based balancing of costs and benefits. for this purpose, we will develop an integrative risk governance framework. the concept of risk governance comprises a broad picture of risk: not only does it include what has been termed "risk management" or "risk analysis", it also looks at how risk-related decision making unfolds when a range of actors is involved, requiring co-ordination and possibly reconciliation between a profusion of roles, perspectives, goals and activities. indeed, the problem-solving capacities of individual actors, be they government, the scientific community, business players, ngos or civil society as a whole, are limited and often unequal to the major challenges facing society today. then the ideas of the operational implementation of normative and factual valuations are continued and a procedure is described that is capable of integrating ethical, risk-based and work-related criteria into a proposed procedural orientation. this procedure is heavily inspired by decision analysis. answering the question about the right action is the field of practical philosophy, ethics. following the usual view in philosophy, ethics describes the theory of the justification of normative statements, i.e. those that guide action (gethmann , mittelstraß , nida-rümelin a , revermann . a system of normative statements is called "morals". ethical judgements therefore refer to the justifiability of moral instructions for action that may vary from individual to individual and from culture to culture (ott ) . basically, humans are purpose-oriented and self-determined beings who act not only instinctively, but also with foresight, and are subject to the moral standards to carry out only those actions that they can classify as good and justifiable (honnefelder ) . obviously, not all people act according to the standards that they themselves see as necessary, but they are capable of doing so. in this context, it is possible for people to act morally because, on the one hand, they are capable of distinguishing between moral and immoral action and, on the other, are largely free to choose between different options for action. whether pursuing a particular instruction for action should be considered as moral or immoral is based on whether the action concerned can be felt and justified to be "reasonable" in a particular situation. standards that cross over situations and that demand universal applicability are referred to as principles here. conflicts may arise between competing standards (in a specific situation), as well as between competing principles, the solution of which, in turn, needs justification (szejnwald-brown et al. ) . providing yardsticks for such justification or examining moral systems with respect to their justifiability is one of the key tasks of practical ethics (gethmann ) . in ethics a distinction is made between descriptive (experienced morality) and prescriptive approaches, i.e. justifiable principles of individual and collective behaviour (frankena , hansen . all descriptive approaches are, generally speaking, a "stock-taking" of actually experienced standards. initially, it is irrelevant whether these standards are justified or not. they gain their normative force solely from the fact that they exist and instigate human action (normative force of actual action). most ethicists agree that no conclusions about general validity can be drawn from the actual existence of standards. this would be a naturalistic fallacy (akademie der wissenschaften , ott ) . nevertheless, experienced morality can be an important indicator of different, equally justifiable moral systems, especially where guidance for cross-cultural behaviour is concerned. this means that the actual behaviour of many people with regard to their natural environment reveals which elements of this environment they value in particular and which they do not. however, in this case, too, the validity of the standards is not derived from their factuality, but merely used as a heurism in order to find an adequate (possibly culture-immanent) justification. but given the variety of cultures and beliefs, how can standards be justified inter-subjectively, i.e. in a way that is equally valid to all? is it not the case that science can only prove or disprove factual statements (and this only to a certain extent), but not normative statements? a brief discourse on the various approaches in ethics is needed to answer this question. first of all, ethics is concerned with two different target aspects: on the one hand, it is concerned with the question of the "success" of one's own "good life", i.e. with the standards and principles that enable a person to have a happy and fulfilled life. this is called eudemonistic ethics. on the other hand, it is concerned with the standards and principles of living together, i.e. with binding regulations that create the conditions for a happy life: the common good. this is called normative ethics (galert , ott . within normative ethics a distinction is made between deontological and teleological approaches when justifying normative statements (höffe ) . deontological approaches are principles and standards of behaviour that apply to the behaviour itself on the basis of an external valuation criterion. it is not the consequences of an action that are the yardstick of the valuation; rather, it is adhering to inherent yardsticks that can be used against the action itself. such external yardsticks of valuation are derived from religion, nature, intuition or common sense, depending on the basic philosophical direction. thus, protection of the biosphere can be seen as a divine order to protect creation (rock , schmitz , as an innate tendency for the emotional attachment of people to an environment with biodiversity (wilson ) , as a directly understandable source of inspiration and joy (ehrenfeld ) or as an educational means of practising responsibility and maintaining social stability (gowdy ) . by contrast, teleological approaches refer to the consequences of action. here, too, external standards of valuation are needed since the ethical quality of the consequences of action also have to be evaluated against a yardstick of some kind. with the most utilitarian approaches (a subset of the teleological approaches) this yardstick is defined as an increase in individual or social benefit. in other schools of ethics, intuition (can the consequence still be desirable?) or the aspect of reciprocity (the so-called "golden rule": "do as you would be done by") play a key role. in the approaches based on logical reasoning (especially in kant), the yardstick is derived from the logic of the ability to generalize or universalize. kant himself is in the tradition of deontological approaches ("good will is not good as a result of what it does or achieves, but just as a result of the intention"). according to kant, every principle that, if followed generally, makes it impossible for a happy life to be conducted is ethically impermissible. in this connection, it is not the desirability of the consequences that captures kant's mind, but the logical inconsistency that results from the fact that the conditions of the actions of individuals would be undermined if everyone were to act according to the same maxims (höffe ) . a number of contemporary ethicists have taken up kant's generalization formula, but do not judge the maxims according to their internal contradictions; rather, they judge them according to the desirability of the consequences to be feared from the generalization (jonas or zimmerli should be mentioned here). these approaches can be defined as a middle course between deontological and teleological forms of justification. in addition to deontological and teleological approaches, there is also the simple solution of consensual ethics, which, however, comprises more than just actually experienced morality. consensual ethics presupposes the explicit agreement of the people involved in an action. everything is allowed provided that all affected (for whatever reason) voluntarily agree. in sexual ethics at the moment a change from deontological ethics to a consensual moral code can be seen. the three forms of normative ethics are shown in figure . . the comparison of the basic justification paths for normative moral systems already clearly shows that professional ethicists cannot create any standards or des- ignate any as clearly right, even if they play a role in people's actual lives. much rather it is the prime task of ethics to ensure on the basis of generally recognized principles (for example, human rights) that all associated standards and behaviour regulations do not contradict each other or a higher order principle. above and beyond this, ethics can identify possible solutions that may occur with a conflict between standards and principles of equal standing. ethics may also reveal interconnections of justification that have proved themselves as examination criteria for moral action in the course of their disciplinary history. finally, many ethicists see their task as providing methods and procedures primarily of an intellectual nature by means of which the compatibility or incompatibility of standards within the framework of one or more moral systems can be completed. unlike the law, the wealth of standards of ethics is not bound to codified rules that can be used as a basis for such compatibility examinations. every normative discussion therefore starts with the general issues that are needed in order to allow individuals a "good life" and, at the same time, to give validity to the principles required to regulate the community life built on common good. but how can generally binding and inter-subjectively valid criteria be made for the valuation of "the common good"? in modern pluralistic societies, it is increasingly difficult for individuals and groups of society to draw up or recognize collectively binding principles that are perceived by all equally as justifiable and as self-obliging (hartwich and wewer , zilleßen ) . the variety of lifestyle options and subjectiernization. with increasing technical and organizational means of shaping the future, the range of behaviour options available to people also expands. with the increasing plurality of lifestyles, group-specific rationalities emerge that create their own worldviews and moral standards, which demand a binding nature and validity only within a social group or subculture. the fewer cross-society guiding principles or behaviour orientations are available, the more difficult is the process of agreement on collectively binding orientations for action. however, these are vital for the maintenance of economic cooperation, for the protection of the natural foundations of life and for the maintenance of cohesion in a society. no society can exist without the binding specification of minimum canons of principles and standards. but how can agreement be reached on such collectively binding principles and standards? what criteria can be used to judge standards? the answers to this question depend on whether the primary principles, in other words, the starting point of all moral systems, or secondary principles or standards, i.e. follow-on standards that can be derived from the primary principles, are subjected to an ethical examination. primary principles can be categorical or compensatory (capable of being compensated). categorical principles are those that must not be infringed under any circumstances, even if other prin- fication of meaning (individualization) are accompanying features of mod-ciples would be infringed as a result. the human right to the integrity of life could be named here as an example. compensatory principles are those where temporary or partial infringement is acceptable, provided that as a result the infringement of a principle of equal or higher ranking is avoided or can be avoided. in this way certain freedom rights can be restricted in times of emergency. in the literature on ethical rules, one can find more complex and sophisticated classifications of normative rules. for our purpose to provide a simple and pragmatic framework, the distinction in four categories (principles and standards; categorical and compensatory) may suffice. this distinction has been developed from a decision-analytical perspective. but how can primary principles be justified as equally valid for all people? although many philosophers have made proposals here, there is a broad consensus today that neither philosophy nor any other human facility is capable of stating binding metacriteria without any doubt and for all people, according to which such primary principles should be derived or examined (mittelstraß ) . a final justification of normative judgements cannot be achieved by logical means either, since all attempts of this kind automatically end either in a logical circle, in an unending regression (vicious cycle) or in a termination of the procedure and none of these alternatives is a satisfactory solution for final justification (albert ). the problem of not being able to derive finally valid principles definitively, however, seems to be less serious than would appear at first glance. because, regardless of whether the basic axioms of moral rules are taken from intuition, observations of nature, religion, tradition reasoning or common sense, they have broadly similar contents. thus, there is broad consensus that each human individual has a right to life, that human freedom is a high-value good and that social justice should be aimed at. but there are obviously many different opinions about what these principles mean in detail and how they should be implemented. in spite of this plurality, however, discerning and well-intentioned observers can usually quickly agree, whether one of the basic principles has clearly been infringed. it is more difficult to decide whether they have clearly been fulfilled or whether the behaviour to be judged should clearly be assigned to one or several principles. since there is no finally binding body in a secular society that can specify primary principles or standards ex cathedra, in this case consensus among equally defendable standards or principles can be used (or pragmatically under certain conditions also majority decisions). ethical considerations are still useful in this case as they allow the test of generalization and the enhancement of awareness raising capabilities. in particular, they help to reveal the implications of such primary principles and standards. provided that primary principles are not concerned (such as human rights), the ethical discussion largely consists of examining the compatibility of each of the available standards and options for action with the primary principles. in this connection, the main concerns are a lack of contradictions (consistency), logical consistency (deductive validity), coherence (agreement with other principles that have been recognized as correct) and other, broadly logical criteria (gethmann ) . as the result of such an examination it is entirely possible to reach completely different conclusions that all correspond to the laws of logic and thus justify new plurality. in order to reach binding statements or valuations here the evaluator can either conduct a discussion in his "mind" and let the arguments for various standards compete with each other (rather like a platonic dialogue) or conduct a real discussion with the people affected by the action. in both cases the main concern is to use the consensually agreed primary principles to derive secondary principles of general action and standards of specific action that should be preferred over alternatives that can be equally justified. a plurality of solutions should be expected especially because most of the concrete options for action comprise only a gradual fulfilment and infringement of primary principles and therefore also include conflicting values. for value conflicts at the same level of abstraction there are, by definition, no clear rules for solution. there are therefore frequently conflicts between conserving life through economic development and destroying life through environmental damage. since the principle of conserving life can be used for both options a conflict is unavoidable in this case. to solve the conflicts, ethical considerations, such as the avoidance of extremes, staggering priorities over time or the search for third solutions can help without, however, being able to convincingly solve this conflict in principle to the same degree for all (szejnwald-brown et al. ) . these considerations lead to some important conclusions for the matter of the application of ethical principles to the issue of human action with regard to the natural environment. first of all, it contradicts the way ethics sees itself to develop ethics of its own for different action contexts. just as there can be no different rules for the logic of deduction and induction in nomological science, depending on which object is concerned, it does not make any sense to postulate an independent set of ethics for the environment (galert ) . justifications for principles and moral systems have to satisfy universal validity (nida-rümelin b). furthermore, it is not very helpful to call for a special moral system for the environment since this -like every other moral system -has to be traceable to primary principles. instead, it makes sense to specify the generally valid principles that are also relevant with regard to the issue of how to deal with the natural environment. at the same time standards should be specified that are appropriate to environmental goods and that reflect those principles that are valid beyond their application to the environment. as implied above, it does not make much sense to talk about an independent set of environmental ethics. much rather, general ethics should be transferred to issues relating to the use of the environment (hargrove ) . three areas are usually dealt with within the context of environmental ethics (galert ): • environmental protection, i.e. the avoidance or alleviation of direct or indirect, current or future damage and pollution resulting from anthropogenic emissions, waste or changes to the landscape, including land use, as well as the long-term securing of the natural foundations of life for people and other living creatures (birnbacher a ). • animal protection, i.e. the search for reasonable and enforceable standards to avoid or reduce pain and suffering in sentient beings (krebs , vischer ). • nature conservation, i.e. the protection of nature against the transforming intervention of human use, especially all measures to conserve, care for, promote and recreate components of nature deemed to be valuable, including species of flora and fauna, biotic communities, landscapes and the foundations of life required there (birnbacher a) . regardless which of these three areas are addressed we need to explore which primary principles be applied to them. when dealing with the environment, the traditional basic and human rights, as well as the civil rights that have been derived from them, should be just as much a foundation of the consideration as other areas of application in ethics. however, with regard to the primary principles there is a special transfer problem when addressing human interventions into nature and the environment: does the basic postulate of conservation of life apply only to human beings, to all other creatures or to all elements of nature, too? this question does not lead to a new primary principle, as one may suspect at first glance. much rather, it is concerned with the delineation of the universally recognized principle of the conservation of life that has already been specified in the basic rights canon. are only people included in this principle (this is the codified version valid in most legal constitutions today) or other living creatures, too? and if yes, which ones? should non-living elements be included as well? when answering this question, two at first sight contradictory positions can be derived: anthropocentrism and physiocentrism (taylor , ott , galert . the anthropocentric view places humans and their needs at the fore. nature's own original demands are alien to this view. interventions in nature are allowed if they are useful to human society. a duty to make provisions for the future and to conserve nature exists in the anthropocentric world only to the extent that natural systems are classed as valuable to people today and subsequent generations and that nature can be classed as a means and guarantor of human life and survival (norton , birnbacher b . in the physiocentric concept, which forms an opposite pole to the anthropocentric view, the needs of human beings are not placed above those of nature. here, every living creature, whether humans, animals or plants, have intrinsic rights with regard to the chance to develop their own lives within the framework of a natural order. merit for protection is justified in the physiocentric view by an inner value that is unique to each living creature or the environment in general. nature has a value of its own that does not depend on the functions that it fulfils today or may fulfil later from a human society's point of view (devall and sessions , callicott , rolston , meyer-abich . each of these prevailing understandings of the human-nature relationship has implications that are decisive for the form and extent of nature use by humans (elliot , krebs . strictly speaking, it could be concluded from the physiocentric idea that all human interventions in nature have to be stopped so that the rights of other creatures are not endangered. yet, not even extreme representatives of a physiocentric view would go so far as to reject all human interventions in nature because animals, too, change the environment by their ways of life (e.g. the elephant prevents the greening of the savannah). the central postulate of a physiocentric view is the gradual minimization of the depth of interventions in human use of nature. the only interventions that are permitted are those that contribute to directly securing human existence and do not change the fundamental composition of the surrounding natural environment. if these two criteria were taken to the extreme, neither population development beyond the boundaries of biological carrying capacity nor a transformation of natural land into pure agricultural land would be allowed. such a strict interpretation of physiocentrism would lead to a radical reversal of human history so far and is not compatible with the values and expectations of most people. the same is true for the unlimited transfer of anthropocentrism to dealings with nature. in this view, the use of natural services is subjected solely to the individual cost-benefit calculation. this can lead to unscrupulous exploitation of nature by humans with the aim of expanding human civilization. both extremes quickly lead to counter-intuitive implications. when the issue of environmental design and policy is concerned, anthropocentric and physiocentric approaches in their pure form are found only rarely, much rather they occur in different mixtures and slants. the transitions between the concepts are fluid. moderate approaches certainly take on elements from the opposite position. it can thus be in line with a fundamentally physiocentric perspective if the priority of human interests is not questioned in the use of natural resources. it is also true that the conclusions of a moderate form of anthropocentrism can approach the implications of the physiocentric view. table . provides an overview of various types of anthropocentric and physiocentric perspectives. if we look at the behaviour patterns of people in different cultures, physiocentric or anthropocentric basic positions are rarely maintained consistently (bargatzky and kuschel ; on the convergence theory: birnbacher ) . in the strongly anthropocentric countries in the west, people spend more money on the welfare and health of their own pets than on saving human lives in other countries. in the countries of the far east that are characterized by physiocentrism, nature is frequently exploited even more radically than in the industrialized countries of the west. this inconsistent action is not a justification for one view or the other, it is just a warning for caution when laying down further rules for use so that no extreme -and thus untenable -demands be made. also from an ethical point of view, radical anthropocentrism should be rejected just as much as radical physiocentrism. if, to take up just one argument, the right to human integrity is largely justified by the fact that causing pain by others should be seen as something to avoid, this consideration without a doubt has to be applied to other creatures that are also capable of feeling pain (referred to as: pathocentrism). here, therefore, pure anthropocentrism cannot convince. in turn, with a purely physiocentric approach the primary principles of freedom, equality and human dignity could not be maintained at all if every part of living nature were equally entitled to use the natural environment. under these circumstances people would have to do without agriculture, the conversion of natural land into agricultural land and breeding farm animals and pets in line with human needs. as soon table . different perspectives on nature. adapted from renn and goble ( : ). as physiocentrism is related to species and not to individuals as is done in some biocentric perspectives human priority is automatically implied; because where human beings are concerned, nearly all schools of ethics share the fundamental moral principle of an individual right to life from birth. if this right is not granted to individual animals or plants, a superiority of the human race is implicitly assumed. moderate versions of physiocentrism acknowledge a gradual de-escalation with respect to the claim of individual table . different perspectives on nature (continued). adapted from renn and goble ( : ). life protection. the extreme forms of both physiocentrism and anthropocentrism are therefore not very convincing and are hardly capable of achieving a global consensus. this means that only moderate anthropocentrism or moderate biocentrism should be considered. the image of nature that is used as a basis for the considerations in this section emphasizes the uniqueness of human beings vis-à-vis physiocentric views, but does not imply carte blanche for wasteful and careless dealings with nature. this moderate concept derives society's duty to conserve nature -also for future generations -from the life-preserving and life-enhancing meaning of nature for society. this is not just concerned with the instrumental value of nature as a "store of resources", it is also a matter of the function of nature as a provider of inspiration, spiritual experience, beauty and peace (birnbacher and schicha ) . in this context it is important that human beings -as the addressees of the moral standard -do not regard nature merely as material and as a way towards their own self-realization, but can also assume responsibility for conservation of their cultural and so-cial function, as well as their existential value above and beyond the objective and technically available benefits (honnefelder ) . one of the first people to express this responsibility of human stewardship of nature in an almost poetic way was the american ecologist aldo leopold, who pointed out people's special responsibility for the existence of nature and land as early as the s with the essay "the conservation ethics". his most well-known work "a sand county almanac" is sustained by the attempt to observe and assess human activities from the viewpoint of the land (a mountain or an animal). this perspective was clearly physiocentric and revealed fundamental insights about the relationship between humans and nature on the basis of empathy and shifting perspectives. his point of view had a strong influence on american environmental ethics and the stance of conservationists. although this physiocentric perspective raises many concerns, the idea of stewardship has been one of the guiding ideas for the arguments used in this section (pickett et al. ) . we are morally required to exercise a sort of stewardship over living nature, because nature cannot claim any rights for itself, but nevertheless has exceptional value that is important to man above and beyond its economic utility value (hösle ) . since contemporary society and the generations to come certainly use, or will use, more natural resources than would be compatible with a lifestyle in harmony with the given natural conditions, the conversion of natural land into anthropogenically determined agricultural land cannot be avoided (mohr ) . many people criticized human interventions into natural cycles as infringements of the applicable moral standards of nature conservation (for example, fastened onto the postulate of sustainability). but we should avoid premature conclusions here, as can be seen with the example of species protection. for example, where natural objects or phenomena are concerned that turn out to be a risk to human or non-human living creatures, the general call for nature conservation is already thrown into doubt (gale and cordray ) . not many people would call the eradication of cholera bacteria, hiv viruses and other pathogens morally bad (mittelstraß ) if remaining samples were kept under lock and key in laboratories. also, combating highly evolved creatures, such as cockroaches or rats meets with broad support if we ignore the call for the complete eradication of these species for the time being. an environmental initiative to save cockroaches would not be likely to gain supporters. if we look at the situation carefully, the valuation of human behaviour in these examples results from a conflict. because the conservation of the species competes with the objective of maintaining human health or the objective of a hygienic place to live, two principles, possibly of equal ranking, come face to face. in this case the options for action, which may all involve a gradual infringement of one or more principles, would have to be weighed up against each other. a general ban on eradicating a species can thus not be justified ethically, in the sense of a categorical principle, unless the maintenance of human health were to be given lower priority than the conservation of a species. with regard to the issue of species conservation, therefore, different goods have to be weighed up against each other. nature itself cannot show society what it is essential to conserve and how much nature can be traded for valuable commodities. humans alone are responsible for a decision and the resulting conflicts between competing objectives. appreciation and negotiation processes are therefore the core of the considerations about the ethical justification of rules for interventions. but this does not mean that there is no room for categorical judgements along the lines of "this or that absolutely must be prohibited" in the matter of human interventions into the natural environment. it follows on from the basic principle of conserving human life that all human interventions that threaten the ability of the human race as a whole, or a significant number of individuals alive today or in the future, to exist should be categorically prohibited. this refers to intervention threats to the systemic functions of the biosphere. such threats are one of the guiding principles that must not be exceeded under any circumstances, even if this excess were to be associated with high benefits. in the language of ethics this is a categorical principle, in the language of economics a good that is not capable of being traded. the "club" of categorical prohibitions should, however, be used very sparingly because plausible trade-offs can be thought up for most principles, the partial exceeding of which appears intuitively. in the case of threats to existence, however, the categorical rejection of the behaviour that leads to this is obvious. but what does the adoption of categorical principles specifically mean for the political moulding of environmental protection? in the past, a number of authors have tried to specify the minimum requirements for an ethically responsible moral system with respect to biosphere use. these so-called "safe minimum standards" specify thresholds for the open-ended measurement scale of the consequences of human interventions that may not be ex-ceeded even if there is a prospect of great benefits (randall , randall and farmer ) . in order to be able to specify these thresholds in more detail the breakdown into three levels proposed by the german scientific council for global environmental change is helpful (wbgu ) . these levels are: • the global bio-geochemical cycles in which the biosphere is involved as one of the causes, modulator or "beneficiary"; • the diversity of ecosystems and landscapes that have key functions as bearers of diversity in the biosphere; and • the genetic diversity and the species diversity that are both "the modelling clay of evolution" and basic elements of ecosystem functions and dynamics. where the first level is concerned, in which the functioning of the global ecosystem is at stake, categorical principles are obviously necessary and sensible, provided that no one wants to shake the primary principle of the permanent preservation of the human race. accordingly, all interventions in which important substance or energy cycles are significantly influenced at a global level and where globally effective negative impacts are to be expected are categorically prohibited. usually no stringently causal evidence of the harmful nature of globally relevant information is needed; justified suspicion of such harmfulness should suffice. later in this chapter we will make a proposal for risk valuation and management how the problem of uncertainty in the event of possible catastrophic damage potential should be dealt with (risk type cassandra). on the second level, the protection of ecosystems and landscapes, it is much more difficult to draw up categorical rules. initially, it is obvious that all interventions in landscapes in which the global functions mentioned on the first level are endangered must be avoided. above and beyond this, it is wise from a precautionary point of view to maintain as much ecosystem diversity as possible in order to keep the degree of vulnerability to the unforeseen or even unforeseeable consequences of anthropogenic and nonanthropogenic interventions as low as possible. even though it is difficult to derive findings for human behaviour from observations of evolution, the empirically proven statement "he who places everything on one card, always loses in the long run" seems to demonstrate a universally valid insight into the functioning of systemically organized interactions. for this reason, the conservation of the natural diversity of ecosystems and landscape forms is a categorical principle, whereas the depth of intervention allowed should be specified on the basis of principles and standards capable of compensation. the same can be said for the third level, genetic and species protection. here too, initially the causal chain should be laid down: species conservation, landscape conservation, maintaining global functions. wherever this chain is unbroken, a categorical order of conservation should apply. these species could be termed primary key species. this includes such species that are not only essential for the specific landscape type in which they occur, but also for the global cycles above and beyond this specific landscape type thanks to their special position in the ecosystem. probably, it will not be possible to organize all species under this functional contribution to the surrounding ecosystem, but we could also think of groups of species, for example, humus-forming bacteria. in second place there are the species that characterize certain ecosystems or landscapes. here they are referred to as secondary key species. they, too, are under special protection that is not necessarily under categorical reservations. their function value, however, is worthy of special attention. below these two types of species there are the remaining species that perform ecosystem functions to a greater or lesser extent. what this means for the worthiness for protection of these species and the point at which the precise limit for permitted intervention should be drawn, is a question that can no longer be solved with categorical principles and standards, but with the help of compensatory principles and standards. generally, here, too, as with the issue of ecosystem and landscape protection, the conservation of diversity as a strategy of "reinsurance" against ignorance, global risks and unforeseeable surprises is recommended. it remains to be said that from a systemic point of view, a categorical ban has to apply to all human interventions where global closed loops are demonstrably at risk. above and beyond this, it makes sense to recognize the conservation of landscape variety (also of ecosystem diversity within landscapes) and of genetic variety and species diversity as basic principles, without being able to make categorical judgements about individual landscape or species types as a result. in order to evaluate partial infringements of compensatory principles or standards, which are referred to in the issue of environmental protection, we need rules for decision making that facilitate the balancing process necessary to resolve compensatory conflicts. in the current debate about rules for using the environment and nature, it is mainly teleological valuation methods that are proposed (hubig , ott . these methods are aimed at: • estimating the possible consequences of various options for action at all dimensions relevant to potentially affected people; • recording the infringements or fulfilments of these expected consequences in the light of the guiding standards and principles; and • then weighing them according to an internal key so that they can be weighed up in a balanced way. on the positive side of the equation, there are the economic benefits of an intervention and the cultural values created by use, for example, in the form of income, subsistence (self-sufficiency) or an aesthetically attractive landscape (parks, ornamental gardens, etc.); on the negative side, there are the destruction of current or future usage potentials, the loss of unknown natural resources that may be needed in the future and the violation of aesthetic, cultural or religious attributes associated with the environment and nature. there are therefore related categories on both sides of the equation: current uses vs. possible uses in the future, development potentials of current uses vs. option values for future use, shaping the environment by use vs. impairments to the environment as a result of alternative use, etc. with the same or similar categories on the credit and debit side of the balance sheet the decision is easy when there is one option that performs better or worse than all the other options for all categories. although such a dominant (the best for all categories) or sub-dominant option (the worst for all categories) is rare in reality, there are examples of dominant or sub-dominant solutions. thus, for example, the overfelling of the forests of kalimantan on the island of borneo in indonesia can be classed as a sub-dominant option since the short-term benefit, even with extremely high discount rates, is in no proportion to the long-term losses of benefits associated with a barren area covered in imperata grass. the recultivation of a barren area of this kind requires sums many times the income from the sale of the wood, including interest. apparently there are no cultural, aesthetic or religious reasons for conversion of primary or secondary woodland into grassland. this means that the option of deforestation should be classed as of less value than alternative options for all criteria, including economic and social criteria. at best, we can talk about a habit of leaving rainforests, as a "biotope not worthy of conservation", to short-term use. but habit is not a sound reason for the choice of any sub-optimum option. as mentioned at the start of this chapter, habit as experienced morality, does not have any normative force, especially when this is based on the illusion of the marginality of one's own behaviour or ignorance about sustainable usage forms. but if we disregard the dominant or sub-dominant solutions, an appreciation between options that violate or fulfil compensatory standards and principles depends on two preconditions: best possible knowledge of the consequences (what happens if i choose option a instead of option b?) and a transparent, consistent rationale for weighing up these consequences as part of a legitimate political decision process (are the foreseeable consequences of option a more desirable or bearable than the consequences of option b?) (akademie der wissenschaften ). adequate knowledge of the consequences is needed in order to reveal the systemic connections between resource use, ecosystem reactions to human interventions and socio-cultural condition factors (wolters ) . this requires interdisciplinary research and cooperation. the task of applied ecological research, for example, is to show the consequences of human intervention in the natural environment and how ecosystems are burdened by different interventions and practices. the economic approach provides a benefit-oriented valuation of natural and artificial resources within the context of production and consumption, as well as a valuation of transformation processes according to the criterion of efficiency. cultural and social sciences examine the feedback effects between use, social development and cultural self-perception. they illustrate the dynamic interactions between usage forms, socio-cultural lifestyles and control forms. interdisciplinary, problem-oriented and system-related research contribute to forming a basic stock of findings and insights about functional links in the relationship between human interventions and the environment and also in developing constructive proposals as to how the basic question of an ethically justified use of the natural environment can be answered in agreement with the actors concerned (wbgu ) . accordingly, in order to ensure sufficient environmental protection, scientific research, but especially transdisciplinary system research at the interface between natural sciences and social sciences is essential. bringing together the results of interdisciplinary research, the policy-relevant choice of knowledge banks and balanced interpretation in an environment of uncertainty and ambivalence are difficult tasks that primarily have to be performed by the science system itself. how this can happen in a way that is methodslogically sound, receptive to all reasonable aspects of interpretation and yet subjectively valid will be the subject of section . . . but knowledge alone does not suffice. in order to be able to act effectively and efficiently while observing ethical principles, it is necessary to shape the appreciation process between the various options for action according to rational criteria (gethmann ) . to do this it is, first of all, necessary to identify the dimensions that should be used for a valuation. the discussion about the value dimensions to be used as a basis for valuation is one of the most popular subjects within environmental ethics. to apply these criteria in risk evaluation and to combine the knowledge aspects about expected consequences of different behavioural options with the ethical principles is the task of what we have called risk governance. what contribution do ethics make towards clarifying the prospects and limits of human interventions into the natural environment? the use of environmental resources is an anthropological necessity. human consciousness works reflexively and humans have developed a causal recognition capacity that enables them to record cause and effect anticipatively and to productively incorporate assessed consequences in their own action. this knowledge is the motivating force behind the cultural evolution and the development of technologies, agriculture and urbanization. with power over an ever-increasing potential of design and intervention in nature and social affairs over the course of human history, the potential for abuse and exploitation has also grown. whereas this potential was reflected in philosophical considerations and legal standards at a very early stage with regard to moral standards between people, the issue of human responsibility towards nature and the environment has only become the subject of intensive considerations in recent times. ethical considerations are paramount in this respect. on the one hand, they offer concrete standards for human conduct on the bases of criteria that can be generalized, and, on the other hand, they provide procedural advice about a rational and decision-and policy-making process. a simple breakdown into categorical rules and prohibitions that are capable of being compensated can assist decision makers for the justification of principles and standards on environmental protection. as soon as human activities exceed the guidelines of the categorical principles, there is an urgent need for action. how can we detect whether such an excess has happened and how it can be prevented from the very outset that these inviolable standards and principles be exceeded? here are three strategies of environmental protection to be helpful for the implementation of categor-ical guidelines. the first strategy is that of complete protection with severe restrictions of all use by humans (protection priority). the second strategy provides for a balanced relationship between protection and use, where extensive resource use should go hand in hand with the conservation of the ecosystems concerned (equal weight). the third strategy is based on optimum use involving assurance of continuous reproduction. the guiding principle here would be an intensive and, at the same time, sustainable, i.e. with a view to the long term, use of natural resources (use priority). the following section will present a framework for applying these principles into environmental decision making under risk. the main line of argument is that risk management requires an analytic-deliberative approach for dealing effectively and prudently with environmental risks. assessing potential consequences of human interventions and evaluating their desirability on the basis of subsequent knowledge and transparent valuation criteria are two of the central tasks of a risk governance process. however, the plural values of a heterogeneous public and people's preferences have to be incorporated in this process. but how can this be done given the wealth of competing values and preferences? should we simply accept the results of opinion polls as the basis for making political decisions? can we rely on risk perception results to judge the seriousness of pending risks? or should we place all our faith in professional risk management? if we turn to professional help to deal with plural value input, economic theory might provide us an answer to this problem. if environmental goods are made individual and suitable for the market by means of property rights, the price that forms on the market ensures an appropriate valuation of the environmental good. every user of this good can then weigh up whether he is willing to pay the price or would rather not use the good. with many environmental goods, however, this valuation has to be made by collective action, because the environmental good concerned is a collective or open access good. in this case a process is needed that safeguards the valuation and justifies it to the collective. however, this valuation cannot be determined with the help of survey results. although surveys are needed to be able to estimate the breadth of preferences and people's willingness to pay, they are insufficient for a derivation of concrete decision-making criteria and yardsticks for evaluating the tolerability of risks to human health and the environment. • firstly, the individual values are so widely scattered that there is little sense in finding an average value here. • secondly, the preferences expressed in surveys change much within a short time, whereas ethical valuations have to be valid for a long time. • thirdly, as outlined in the subsection on risk perception, preferences are frequently based on flawed knowledge or ad hoc assumptions both of which should not be decisive according to rational considerations. what is needed, therefore, is a gradual process of assigning trade-offs in which existing empirical values are put into a coherent and logically consistent form. in political science and sociological literature reference is mostly made to three strategies of incorporating social values and preferences in rational decision-making processes (renn ) . firstly, a reference to social preferences is viewed solely as a question of legitimate procedure (luhmann , vollmer . the decision is made on the basis of formal decision-making process (such as majority voting). if all the rules have been kept, a decision is binding, regardless of whether the subject matter of the decision can be justified or whether the people affected by the decision can understand the justification. in this version, social consensus has to be found only about the structure of the procedures; the only people who are then involved in the decisions are those who are explicitly legitimated to do so within the framework of the procedure decided upon. the second strategy is to rely on the minimum consensuses that have developed in the political opinion-forming process (muddling through) (lindbloom (lindbloom , . in this process, only those decisions that cause the least resistance in society are considered to be legitimate. in this version of social pluralism groups in society have an influence on the process of the formation of will and decision making to the extent that they provide proposals capable of being absorbed, i.e. adapted to the processing style of the political system, and that they mobilize public pressure. the proposal that then establishes itself in politics is the one that stands up best in the competition of proposals, i.e. the one that entails the fewest losses of support for political decision makers by interest groups. the third strategy is based on the discussion between the groups involved (habermas , renn ). in the communicative exchange among the people involved in the discussion a form of communicative rationality that everyone can understand evolves that can serve as a justification for collectively binding decisions. at the same time, discursive methods claim to more appropriately reflect the holistic nature of human beings and also to provide fair access to designing and selecting solutions to problems. in principle, the justification of standards relevant to decisions is linked to two conditions: the agreement of all involved and substantial justification of the statements made in the discussion (habermas ) . all three strategies of political control are represented in modern societies to a different extent. legitimation conflicts mostly arise when the three versions are realized in their pure form. merely formally adhering to decisionmaking procedures without a justification of content encounters a lack of understanding and rejection among the groups affected especially when they have to endure negative side effects or risks. then acceptance is refused. if, however, we pursue the opposite path of least resistance and base ourselves on the route of muddling through we may be certain of the support of the influential groups, but, as in the first case, the disadvantaged groups will gradually withdraw their acceptance because of insufficient justification of the decision. at the same time, antipathy to politics without a line or guidance is growing, even the affected population. the consequence is political apathy. the third strategy of discursive control faces problems, too. although in an ideal situation it is suitable for providing transparent justifications for the decision-making methods and the decision itself, in real cases the conditions of ideal discourse can rarely be adhered to (wellmer ) . frequently, discussions among strategically operating players lead to a paralysis of practical politics by forcing endless marathon meetings with vast quantities of points of order and peripheral contributions to the discussion. the "dictatorship of patience" (weinrich ) ultimately determines which justifications are accepted by the participants. the public becomes uncertain and disappointed by such discussions that begin with major claims and end with trivial findings. in brief: none of the three ways out of the control dilemma can convince on its own; as so often in politics, everything depends on the right mixture. what should a mixture of the three elements (due process, pluralistic muddling through and discourse) look like so that a maximum degree of rationality can come about on the basis of social value priorities? a report by the american academy of sciences on the subject of "understanding environmental risks" (national research council ) comes to the conclusion that scientifically valid and ethically justified procedure for the collective valuation of options for risk handling can only be realized within the context of -what the authors coin -an analytic-deliberative process. analytic means that the best scientific findings about the possible consequences and conditions of collective action are incorporated in the negotiations; deliberative means that rationally and ethically transparent criteria for making trade-offs are used and documented externally. moreover, the authors consider that fair participation by all groups concerned is necessary to ensure that the different moral systems that can legitimately exist alongside each other should also be incorporated in the process. to illustrate the concept of analytic-deliberative decision making consider a set of alternative options or choices, from which follow consequences (see basic overview in dodgson et al. ) . the relationship between the choice made, and the consequences that follow from this choice, may be straightforward or complex. the science supporting environmental policy is often complicated, across many disciplines of science and engineering, and also involving human institutions and economic interactions. because of limitations in scientific understanding and predictive capabilities, the consequences following a choice are normally uncertain. finally, different individuals and groups within society may not agree on how to evaluate the consequences -which may involve a detailed characterization of what happens in ecological, economic, and human health terms. we shall describe consequences as ambiguous when there is this difficulty in getting agreement on how to interpret and evaluate them. this distinction has been further explained in chapter (see also klinke and renn ) . environmental assessment and environmental decision making inherently involve these difficulties of complexity, uncertainty, and ambiguity (klinke and renn ) . in some situations where there is lots of experience, these difficulties may be minimal. but in other situations these difficulties may constitute major impediments to the decision-making process. to understand how analysis and deliberation interact in an iterative process following the national research council (nrc) report, one must consider how these three areas of potential difficulty can be addressed. it is useful to separate questions of evidence with respect to the likelihood, magnitude of consequences and related characteristics (which can involve complexity and uncertainty) from valuation of the consequences (i.e. ambiguity). for each of the three areas there are analytical tools that can be helpful in identifying, characterizing and quantifying cause-effect relationships. some of these tools have been described in chapter . the integration of these tools of risk governance into a consistent procedure will be discussed in the next subsections. the possibility to reach closure on evaluating risks to human health or the environment rests on two conditions: first, all participants need to achieve closure on the underlying goal (often legally prescribed, such as prevention of health detriments or guarantee of an undisturbed environmental quality, for example, purity laws for drinking water); secondly, they need to agree with the implications derived from the present state of knowledge (whether and to what degree the identified hazard impacts the desired goal). dissent can result from conflicting values as well as conflicting evidence. it is crucial in environmental risk management to investigate both sides of the coin: the values that govern the selection of the goal and the evidence that governs the selection of cause-effect claims. strong differences in both areas can be expected in most environmental decision-making contexts but also in occupational health and safety and public health risks. so for all risk areas it is necessary to explore why people disagree about what to do -that is, which decision alternative should be selected. as pointed out before, differences of opinion may be focused on the evidence of what is at stake or which option has what kind of consequences. for example: what is the evidence that an environmental management initiative will lead to an improvement, such as reducing losses of agricultural crops to insect pests -and what is the evidence that the management initiative could lead to ecological damage -loss of insects we value, such as bees or butterflies, damage to birds and other predators that feed on insects -and health impacts from the level of pesticides and important nutrients in the food crops we eat? other differences of opinion may be about values -value of food crops that contain less pesticide residue compared to those that contain more, value of having more bees or butterflies, value of maintaining indigenous species of bees or butterflies compared to other varieties not native to the local ecosystem, value ascribed to good health and nutrition, and maybe, value ascribed to having food in what is perceived to be a "natural" state as opposed to containing manufactured chemical pesticides or altered genetic material. separating the science issues of what will happen from the value issues of how to make appropriate trade-offs between ecological, economic, and human health goals can become very difficult. the separation of facts and values in decision making is difficult to accomplish in practical decision situations, since what is regarded as facts includes a preference dependent process of cognitive framing (tversky and kahneman ) and what is regarded as value includes a prior knowledge about the factual implica-tions of different value preferences (fischhoff ) . furthermore, there are serious objections against a clear-cut division from a sociological view on science and knowledge generation (jasanoff ) . particularly when calculating risk estimates, value-based conventions may enter the assessment process. for example, conservative assumptions may be built into the assessment process, so that some adverse effects (such as human cancer from pesticide exposure) are much less likely to be underestimated than overestimated (national research council ) . at the same time, ignoring major sources of uncertainty can evoke a sense of security and overconfidence that is not justified from the quality or extent of the data base (einhorn and hogarth ) . perceptions and world views may be very important, and difficult to sort out from matters of science, especially with large uncertainties about the causes of environmental damage. a combination of analytic and deliberative processes can help explore these differences of opinions relating to complexity, uncertainty, and ambiguity in order to examine the appropriate basis for a decision before the decision is made. most environmental agencies go through an environmental assessment process and provide opportunities for public review and comment. many controversial environmental decisions become the focus of large analytical efforts, in which mathematical models are used to predict the environmental, economic, and health consequences of environmental management alternatives. analysis should be seen as an indispensable complement to deliberative processes, regardless whether this analysis is sophisticated or not. even simple questions need analytic input for making prudent decisions, especially in situations where there is controversy arising from complexity, uncertainty, and ambiguity. in many policy arenas in which problems of structuring human decisions are relevant, the tools of normative decision analysis (da) have been applied. especially in economics, sociology, philosophical ethics, and also many branches of engineering and science, these methods have been extended and refined during the past several decades. (edwards , howard , north , howard et al. , north and merkhofer , behn and vaupel , pinkau and renn , van asselt , jaeger et al. . da is a process for decomposing a decision problem into pieces, starting with the simple structure of alternatives, information, and prefer-ences. it provides a formal framework for quantitative evaluation of alternative choices in terms of what is known about the consequences and how the consequences are valued (hammond et al. , skinner . the procedures and analytical tools of da provide a number of possibilities to improve the precision and transparency of the decision procedure. however, they are subject to a number of limitations. the opportunities refer to: • different action alternatives can be quantitatively evaluated to allow selection of a best choice. such evaluation relies both on a description of uncertain consequences for each action alternative, with uncertainty in the consequences described using probabilities, and a description of the values and preferences assigned to consequences. (explicit characterization of uncertainty and values of consequences) • the opportunity to assure transparency, in that ( ) models and data summarizing complexity (e.g., applicable and available scientific evidence) ( ) probabilities characterizing judgement about uncertainty, and ( ) values (utilities) on the consequences are made explicit and available. so the evaluation of risk handling alternatives can be viewed and checked for accuracy by outside observers. (outside audit enabled of basis for decision) • a complex decision situation can be decomposed into smaller pieces in a formal analytical framework. the level of such composition can range from a decision tree of action alternatives and ensuing consequences that fits on a single piece of paper, to extremely large and complex computerimplemented models used in calculating environmental consequences and ascribing probabilities and values of the consequences. a more complex analysis is more expensive and is less transparent to observers. in principle, with sufficient effort any formal analytical framework can be checked to assure that calculations are made in the way that is intended. (decomposition possible to include extensive detail) on the other hand, there are important limitations: • placing value judgements (utilities) on consequences may be difficult, especially in a political context where loss of life, impairment of health, ecological damage, or similar social consequences are involved. utility theory is essentially an extension of cost-benefit methods from economics to include attitude toward risk. the basic trade-off judgements needed for cost-benefit analysis remain difficult and controversial, and often, inherently subjective. (difficulties in valuing consequences) • assessing uncertainty in the form of a numerical probability also poses difficulties, especially in situations when there is not a statistical data base on an agreed-on model as the basis for the assessment. (difficulty in quantifying uncertainty, assigning probabilities) • the analytical framework may not be complete. holistic or overarching considerations or important details may have been omitted. (analytical framework incomplete) • da is built upon an axiomatic structure, both for dealing with uncertainty (i.e., the axiomatic foundation of probability theory), and for valuing consequences (i.e., the axiomatic basis for von neumann-morgenstern utility theory). especially when the decision is to be made by a group rather than an individual decision maker, rational preferences for the group consistent with the axioms may not exist (the "impossibility" theorem of arrow, ) . so in cases of strong disagreements on objectives or unwillingness to use a rational process, decision analysis methods may not be helpful. decision analytical methods should not be regarded as inherently "mechanical" or "algorithmic", in which analysts obtain a set of "inputs" about uncertainty and valuing consequences, then feed these into a mathematical procedure (possibly implemented in a computer) that produces an "output" of the "best" decision. da can only offer coherent conclusions from the information which the decision maker provides by his/her preferences among consequences and his/her state of information on the occurrence of these consequences. where there is disagreement about the preferences or about the information, da may be used to implore the implications of such disagreement. so in application, there is often a great deal of iteration (sensitivity analysis) to explore how differences in judgement should affect the selection of the best action alternative. da thus merely offers a formal framework that can be effective in helping participants in a decision process to better understand the implications of differing information and judgement about complex and uncertain consequences from the choice among the available action alternatives. insight about which factors are most important in selecting among the alternatives is often the most important output of the process, and it is obtained through extensive and iterative exchange between analysts and the decision makers and stakeholders. the main advantage of the framework is that it is based on logic that is both explicit and checkable -usually facilitated by the use of mathematical models and probability calculations. research on human judgement supports the superiority of such procedures for decomposing complex decision problems and using logic to integrate the pieces, rather than relying on holistic judgement on which of the alternatives is best (this is not only true for individual decisions, see heap et al. : ff., jungermann ; but also for collective decisions, see heap et al. : ff., pettit . one should keep in mind, however, that "superior" is measured in accordance with indicator of instrumental rationality, i.e. measuring means-ends effectiveness. if this rationality is appropriate, the sequence suggested by da is intrinsically plausible and obvious. even at the level of qualitative discussion and debate, groups often explore the rationale for different action alternatives. decision analysis simply uses formal quantitative methods for this traditional and common-sense process of exploring the rationale -using models to describe complexity, probability to describe uncertainty, and to deal with ambiguity, explicit valuation of consequences via utility theory and other balancing procedures, such as cost-benefit or cost-effectiveness analyses. by decomposing the problem in logical steps, the analysis permits better understanding of differences in the participants' perspective on evidence and values. da offers methods to overcome these differences, such as resolving questions about underlying science through data collection and research, and encouraging tradeoffs, compromise, and rethinking of values. based on this review of opportunities and shortcomings we conclude that decision analysis provides a suitable structure for guiding discussion and problem formulation, and offers a set of quantitative analytical tools that can be useful for environmental decisions, especially in conjunction with deliberative processes. da can assist decision makers and others involved in, and potentially affected by, the decision (i.e., participants, stakeholders) to deal with complexity and many components of uncertainty, and to address issues of remaining uncertainties and ambiguities. using these methods promises consistency from one decision situation to another, assurance of an appropriate use of evidence from scientific studies related to the environment, and explicit accountability and transparency with respect to those institutionally responsible for the value judgements that drive the evaluation of the alternative choices. collectively the analytical tools provide a framework for a systematic process of exploring and evaluating the decision alternatives -assembling and validating the applicable scientific evidence relevant to what will happen as the result of each possible choice, and valuing how bad or how good these consequences are based on an agreement of common objectives. yet, it does not replace the need for additional methods and processes for including other objectives, such as finding common goals, defining preferences, revisiting assumptions, sharing visions and exploring common grounds for values and normative positions. the value judgements motivating decisions are made explicit and can then be criticized by those who were not involved in the process. to the extent that uncertainty becomes important, it will be helpful to deal with uncertainty in an orderly and consistent way (morgan and henrion ). those aspects of uncertainty that can be modelled by using probability theory (inter-target variation, systematic and random errors in applying inferential statistics, model and data uncertainties) will be spelled out and those that remain in forms of indeterminacies, system boundaries or plain ignorance will become visible and can then be fed into the deliberation process (van asselt , klinke and renn ) . the term deliberation refers to the style and procedure of decision making without specifying which participants are invited to deliberate (national research council (nrc) , rossi ) . for a discussion to be called deliberative it is essential that it relies on mutual exchange of arguments and reflections rather than decision making based on the status of the participants, sublime strategies of persuasion, or social-political pressure. deliberative processes should include a debate about the relative weight of each argument and a transparent procedure for balancing pros and cons (tuler and webler ) . in addition, deliberative processes should be governed by the established rules of a rational discourse. in the theory of communicative action developed by the german philosopher jürgen habermas, the term discourse denotes a special form of a dialogue, in which all affected parties have equal rights and duties to present claims and test their validity in a context free of social or political domination (habermas (habermas , b . a discourse is called rational if it meets the following specific requirements (see mccarthy , habermas a , kemp , webler . all participants are obliged: • to seek a consensus on the procedure that they want to employ in order to derive the final decision or compromise, such as voting, sorting of positions, consensual decision making or the involvement of a mediator or arbitrator; • to articulate and criticize factual claims on the basis of the "state of the art" of scientific knowledge and other forms of problem-adequate knowledge; (in the case of dissent all relevant camps have the right to be represented); • to interpret factual evidence in accordance with the laws of formal logic and analytical reasoning; • to disclose their relevant values and preferences, thus avoiding hidden agendas and strategic game playing; and • to process data, arguments and evaluations in a structured format (for example a decision-analytic procedure) so that norms of procedural rationality are met and transparency can be created. the rules of deliberation do not necessarily include the demand for stakeholder or public involvement. deliberation can be organized in closed circles (such as conferences of catholic bishops, where the term has indeed been used since the council of nicosia), as well as in public forums. it may be wise to use the term "deliberative democracy" when one refers to the combination of deliberation and public or stakeholder involvement (see also cohen , rossi . what needs to be deliberated? firstly, deliberative processes are needed to define the role and relevance of systematic and anecdotal knowledge for making far-reaching choices. secondly, deliberation is needed to find the most appropriate way to deal with uncertainty in environmental decision making and to set efficient and fair trade-offs between potential over-and under-protection. thirdly, deliberation needs to address the wider concerns of the affected groups and the public at large. why can one expect that deliberative processes are better suited to deal with environmental challenges than using expert judgement, political majority votes or relying on public survey data? • deliberation can produce common understanding of the issues or the problems based on the joint learning experience of the participants with respect to systematic and anecdotal knowledge (webler and renn , pidgeon ). • deliberation can produce a common understanding of each party's position and argumentation and thus assist in a mental reconstruction of each actor's argumentation (warren , tuler . the main driver for gaining mutual understanding is empathy. the theory of communicative action provides further insights in how to mobilize empathy and how to use the mechanisms of empathy and normative reasoning to explore and generate common moral grounds (webler ). • deliberation can produce new options and novel solutions to a problem. this creative process can either be mobilized by finding win-win solutions or by discovering identical moral grounds on which new options can grow (renn ) . • deliberation has the potential to show and document the full scope of ambiguity associated with environmental problems. deliberation helps to make a society aware of the options, interpretations, and potential actions that are connected with the issue under investigation (wynne , de marchi and ravetz ) . each position within a deliberative discourse can only survive the crossfire of arguments and counter-arguments if it demonstrates internal consistency, compatibility with the legitimate range of knowledge claims and correspondence with the widely accepted norms and values of society. deliberation clarifies the problem, makes people aware of framing effects, and determines the limits of what could be called reasonable within the plurality of interpretations (skillington ) . • deliberations can also produce agreements. the minimal agreement may be a consensus about dissent (raiffa ) . if all arguments are exchanged, participants know why they disagree. they may not be convinced that the arguments of the other side are true or morally strong enough to change their own position; but they understand the reasons why the opponents came to their conclusion. in the end, the deliberative process produces several consistent and -in their own domain -optimized positions that can be offered as package options to legal decision makers or the public. once these options have been subjected to public discourse and debate, political bodies, such as agencies or parliaments can make the final selection in accordance with the legitimate rules and institutional arrangements such as majority vote or executive order. final selections could also be performed by popular vote or referendum. • deliberation may result in consensus. often deliberative processes are used synonymously with consensus-seeking activities (coglianese ). this is a major misunderstanding. consensus is a possible outcome of deliberation, but not a mandatory requirement. if all participants find a new option that they all value more than the one option that they preferred when entering the deliberation, a "true" consensus is reached (renn ) . it is clear that finding such a consensus is the exception rather than the rule. consensus is either based on a win-win solution or a solution that serves the "common good" and each participant's interests and values better than any other solution. less stringent is the requirement of a tolerated consensus. such a consensus rests on the recognition that the selected decision option might serve the "common good" best, but on the expense of some interest violations or additional costs. in a tolerated consensus some participants voluntarily accept personal or group-specific losses in exchange for providing benefits to all of society. case studies have provided sufficient evidence that deliberation has produced a tolerated consensus solution, particularly in siting conflicts (one example in schneider et al. ) . consensus and tolerated consensus should be distinguished from compromise. a compromise is a product of bargaining where each side gradually reduces its claim to the opposing party until they reach an agreement (raiffa ) . all parties involved would rather choose the option that they preferred before starting deliberations, but since they cannot find a win-win situation or a morally superior alternative they look for a solution that they can "live with" knowing that it is the second or third best solution for them. compromising on an issue relies on full representation of all vested interests. in summary, many desirable products and accomplishments are associated with deliberation (chess et al. ) . depending on the structure of the discourse and the underlying rationale deliberative processes can: • enhance understanding; • generate new options; • decrease hostility and aggressive attitudes among the participants; • explore new problem framing; • enlighten legal policy-makers; • produce competent, fair and optimized solution packages; and • facilitate consensus, tolerated consensus and compromise. in a deliberative setting, participants exchange arguments, provide evidence for their claims and develop common criteria for balancing pros and cons. this task can be facilitated and often guided by using decision analytic tools (overview in merkhofer ) . decision theory provides a logical framework distinguishing action alternatives or options, consequences, likelihood of consequences, and value of consequences, where the valuation can be over multiple attributes that are weighted based on tradeoffs in multi-attribute utility analysis (edwards ) . a sequence of decisions and consequences may be considered, and use of mathematical models for predicting the environmental consequences of options may or may not be part of the process (humphreys , bardach , arvai et al. ): a) the structuring potential of decision analysis has been used in many participatory processes. it helps the facilitator of such processes to focus on one element during the deliberation, to sort out the central from the peripheral elements, provide a consistent reference structure for ordering arguments and observations and to synthesize multiple impressions, observations and arguments into a coherent framework. the structuring power of decision analysis has often been used without expanding the analysis into quantitative modelling. b) the second potential, agenda setting and sequencing, is also frequently applied in participatory settings. it often makes sense to start with problem definition, then develop the criteria for evaluation, generate options, assess consequences of options, and so on. c) the third potential, quantifying consequences, probabilities and relative weights and calculating expected utilities, is more controversial than the other two. whether the deliberative process should include a numerical analysis of utilities or engage the participants in a quantitative elicitation process is contested among participation practitioners . one side claims that quantifying helps participants to be more precise about their judgements and to be aware of the often painful trade-offs they are forced to make. in addition, quantification can make judgements more transparent to outside observers. the other side claims that quantification restricts the participants to the logic of numbers and reduces the complexity of argumentation into a mere trade-off game. many philosophers argue that quantification supports the illusion that all values can be traded off against other values and that complex problems can be reduced to simple linear combinations of utilities. one possible compromise between the two camps may be to have participants go through the quantification exercise as a means to help them clarify their thoughts and preferences, but make the final decisions on the basis of holistic judgements (renn ) . in this application of decision analytic procedures, the numerical results (i.e. for each option the sum over the utilities of each dimension multiplied by the weight of each dimension) of the decision process are not used as expression of the final judgement of the participant, but as a structuring aid to improve the participant's holistic, intuitive judgement. by pointing out potential discrepancies between the numerical model and the holistic judgements, the participants are forced to reflect upon their opinions and search for potential hidden motives or values that might explain the discrepancy. in a situation of major value conflicts, the deliberation process may involve soliciting a diverse set of viewpoints, and judgements need to be made on what sources of information are viewed as responsible and reliable. publication in scientific journals and peer review from scientists outside the government agency are the two most popular methods by which managers or organizers of deliberative processes try to limit what will be considered as acceptable evidence. other methods are to reach a consensus among the participants up front which expertise should be included in the deliberation or to appoint representatives of opposing science camps to explain their differences in public. in many cases, participants have strong reasons for questioning scientific orthodoxy and would like to have different science camps represented. many stakeholders in environmental decisions have access to expert scientists, and often such scientists will take leading roles in criticizing agency science. such discussions need to be managed so that disagreements among the scientific experts can be evaluated in terms of the validity of the evidence presented and the importance to the decision. it is essential in these situations to have a process in place that distinguishes between those evidence claims that all parties agree on, those where the factual base is shared but not its meaning for some quality criterion (such as "healthy" environment), and those where even the factual base is contested (foster ) . in the course of practical risk management different conflicts arise in deliberative settings that have to be dealt with in different ways. the main conflicts occur at the process level (how should the negotiations be conducted?), on the cognitive level (what is factually correct?), the interest level (what benefits me?), the value level (what is needed for a "good" life?) and the normative level (what can i expect of all involved?). these different conflict levels are addressed in this subsection. first of all, negotiations begin by specifying the method that structures the dialogue and the rights and duties of all participants. it is the task of the chairman or organizer to present and justify the implicit rules of the talks and negotiations. above and beyond this, the participants have to specify joint rules for decisions, the agenda, the role of the chairman, the order of hearings, etc. this should always be done according to the consensus principle. all partners in the negotiations have to be able to agree to the method. if no agreement is reached here the negotiations have to be interrupted or reorganized. once the negotiation method has been determined and, in a first stage, the values, standards and objectives needed for judgement have been agreed jointly, then follows the exchange of arguments and counter arguments. in accordance with decision theory, four stages of validation occur: • in a first stage, the values and standards accepted by the participants are translated into criteria and then into indicators (measurement instructions). this translation needs the consensual agreement of all participants. experts are asked to assess the available options with regard to each indicator according to the best of their knowledge (factual correctness). in this context it makes more sense to specify a joint methodological procedure or a consensus about the experts to be questioned than to give each group the freedom to have the indicators answered by their own experts. often many potential consequences remain disputed as a result of this process, especially if they are uncertain. however, the bandwidth of possible opinions is more or less restricted depending on the level of certainty and clarity associated with the issue in question. consensus on dissent is also of help here in separating contentious factual claims from undisputed ones and thus promotes further discussion. • in a second stage, all participating parties are required to interpret bandwidths of impacts to be expected for each criterion. interpretation means linking factual statements with values and interests to form a balanced overall judgement (conflicts of interests and values). this judgement can and should be made separately for each indicator. in this way, each of the chains of causes for judgements can be understood better and criticized in the course of the negotiations. for example, the question of trustworthiness of the respective risk management agencies may play an important role in the interpretation of an expected risk value. then it is the duty of the participating parties to scrutinize the previous performance of the authority concerned and propose institutional changes where appropriate. • third stage: even if there were a joint assessment and interpretation for every indicator, this would by no means signify that agreement is at hand. much rather, the participants' different judgements about decisionmaking options may be a result of different value weightings for the indicators that are used as a basis for the values and standards. for example, a committed environmentalist may give much more weight to the indicator for conservation than to the indicator of efficiency. in the literature on game theory, this conflict is considered to be insoluble unless one of the participants can persuade the other to change his preference by means of compensation payments (for example, in the form of special benefits), transfer services (for example, in the form of a special service) or swap transactions (do, ut des). in reality, however, it can be seen that participants in negotiations are definitely open to the arguments of the other participants (i.e. they may renounce their first preference) if the loss of benefit is still tolerable for them and, at the same time, the proposed solution is considered to be "conducive to the common good", i.e. is seen as socially desirable in public perception. if no consensus is reached, a compromise solution can and should be reached, in which a 'fair' distribution of burdens and profits is accomplished. • fourth stage: when weighing up options for action formal methods of balancing assessment can be used. of these methods, the cost-benefit analysis and the multi-attribute or multi-criteria decision have proved their worth. the first method is largely based on the approach of revealed "preferences", i.e. on people's preferences shown in the past expressed in relative prices, the second on the approach of "expressed preferences", i.e. the explicit indication of relative weightings between the various cost and benefit dimensions (fischhoff et al. ) . but both methods are only aids in weighing up and cannot replace an ethical reflection of the advantages and disadvantages. normative conflicts pose special problems because different evaluative criteria can always be classified as equally justifiable or unjustifiable as explained earlier. for this reason, most ethicists assume that different types and schools of ethical justification can claim parallel validity, it therefore remains up to the groups involved to choose the type of ethically legitimate justification that they want to use (ropohl , renn . nevertheless, the limits of particular justifications are trespassed wherever primary principles accepted by all are infringed (such as human rights). otherwise, standards should be classed as legitimate if they can be defended within the framework of ethical reasoning and if they do not contradict universal standards that are seen as binding for all. in this process conflicts can and will arise, e.g. that legitimate derivations of standards from the perspective of group a contradict the equally legitimate derivations of group b (shrader-frechette ). in order to reach a jointly supported selection of standards, either a portfolio of standards that can claim parallel validity should be drawn up or compensation solutions will have to be created in which one party compensates the other for giving up its legitimate options for action in favour of a common option. when choosing possible options for action or standards, options that infringe categorical principles, for example, to endangering the systematic ability of the natural environment to function for human use in the future and thus exceeding the limits of tolerability are not tolerable even if they imply major benefits to society. at the same time, all sub-dominant options have to be excluded. frequently sub-dominant solutions, i.e. those that perform worse than all other options with regard to all criteria at least in the long term, are so attractive because they promise benefits in the short term although they entail losses in the long term, even if high interest rates are assumed. often people or groups have no choice other than to choose the sub-dominant solution because all other options are closed to them due to a lack of resources. if large numbers of groups or many individuals act in this way, global risks become unmanageable (beck ) . to avoid these risks intermediate financing or compensation by third parties should be considered. the objective of this last section of chapter was to address and discuss the use of decision analytic tools and structuring aids for participatory processes in environmental management. organizing and structuring discourses goes beyond the good intention to have all relevant stakeholders involved in decision making. the mere desire to initiate a two-way communication process and the willingness to listen to stakeholder concerns are not sufficient. discursive processes need a structure that assures the integration of technical expertise, regulatory requirements, and public values. these different inputs should be combined in such a fashion that they contribute to the deliberation process the type of expertise and knowledge that can claim legitimacy within a rational decision-making procedure (von schomberg ). it does not make sense to replace technical expertise with vague public perceptions, nor is it justified to have the experts insert their own value judgements into what ought to be a democratic process. decision analytic tools can be of great value for structuring participatory processes. they can provide assistance in problem structuring, in dealing with complex scientific issues and uncertainty, and in helping a diverse group to understand disagreements and ambiguity with respect to values and preferences. decision analysis tools should be used with care. they do not provide an algorithm to reach an answer as to what is the best decision. rather, decision analysis is a formal framework that can be used for environmental assessment and risk handling to explore difficult issues, to focus debate and further analysis on the factors most important to the decision, and to provide for increased transparency and more effective exchange of information and opinions among the process participants. the basic concepts are relatively simple and can be implemented with a minimum of mathematics (hammond et al. ) . many participation organizers have restricted the use of decision analytic tools to assist participants in structuring problems and ordering concerns and evaluations, and have refrained from going further into quantitative trade-off analysis. others have advocated quantitative modelling as a clarification tool for making value conflicts more transparent to the participants. the full power of decision analysis for complex environmental problem may require mathematical models and probability assessment. experienced analysts may be needed to guide the implementation of these analytical tools for aiding decisions. skilled communicators and facilitators may be needed to achieve effective interaction between analysts and participants in the deliberative process whose exposure to advanced analytical decision aids is much less, so that understanding of both process and substance, and therefore transparency and trust, can be achieved. many risk management agencies are already making use of decision analysis tools. we urge them to use these tools in the context of an iterative, deliberative process with broad participation by the interested and affected parties to the decision in the context of the risk governance framework. the analytical methods, the data and judgement, and the 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Ökologie und ethik. ein versuch praktischer philosophie. ethik in den wissenschaften zur ethischen bewertung von biodiversität. externes gutachten für den wbgu. unveröffentlichtes manuskript decision theory and folk psychology towards a comprehensive conservation theory the limits to safety? culture, politics, learning and manmade disasters environmental standards. scientific foundations and rational procedures of regulation with emphasis on radiological risk management the art and science of negotiation what mainstream economists have to say about the value of biodiversity benefits, costs, and the safe minimum standard of conservation decision analytic tools for resolving uncertainty in the energy debate Ökologisch denken -sozial handeln: die realisierbarkeit einer nachhaltigen entwicklung und die rolle der sozial-und kulturwissenschaften ein diskursives verfahren zur bildung und begründung kollektiv verbindlicher bewertungskriterien a model for an analytic-deliberative process in risk management the challenge of integrating deliberation and expertise: participation and discourse in risk management a regional concept of qualitative growth and sustainability -support for a case study in the german state of baden-württemberg was heißt hier bioethik? tab-brief theologie der natur und ihre anthriopologisch-ethischen konsequenzen values in nature and the nature of value ob man die ambivalenzen des technischen fortschritts mit einer neuen ethik meistern kann? participation run amok: the costs of mass participation for deliberative agency decisionmaking ist die schöpfung noch zu retten? umweltkrise und christliche verantwortung experiences from germany: application of a structured model of public participation in waste management planning environmental ethics politics and the struggle to define: a discourse analysis of the framing strategies of competing actors in a "new introduction to decision analysis corporate environmentalism in a global economy respect for nature. a theory of environmental ethics meanings, understandings, and interpersonal relationships in environmental policy discourse. doctoral dissertation designing an analytic deliberative process for environmental health policy making in the u.s. nuclear weapons complex the framing of decisions and the psychology of choice perspectives on uncertainty and risk akzeptanzbeschaffung: verfahren und verhandlungen the erosion of the valuespheres. the ways in which society copes with scientific, moral and ethical uncertainty can participatory democracy produce better selves? psychological dimensions of habermas discursive model of democracy welt im wandel: erhaltung und nachhaltige nutzung der biosphäre. jahresgutachten discourse in citizen participation. an evaluative yardstick the craft and theory of public participation: a dialectical process a brief primer on participation: philosophy and practice system, diskurs, didaktik und die diktatur des sitzfleisches konsens als telos der sprachlichen kommunikation? in: giegel biophilia: the human bond with other species rio" oder die moralische verpflichtung zum erhalt der natürlichen vielfalt risk and social learning: reification to engagement die modernisierung der demokratie im zeichen der umweltproblematik wandelt sich die verantwortung mit technischem wandel? key: cord- -yeih tfo authors: page, stephen j. title: tourism today: why is it a global phenomenon embracing all our lives? date: - - journal: tourism management doi: . /b - - - - . - sha: doc_id: cord_uid: yeih tfo nan the new millennium has witnessed the continued growth of interest in how people spend their spare time, especially their leisure time and nonwork time. some commentators have gone as far as to suggest that it is leisure time -how we use it and its meaning to individuals and familiesthat defines our lives, as a focus for non-work activity. this reflects a growing interest in what people consume in these non-work periods, particularly those times that are dedicated to travel and holidays which are more concentrated periods of leisure time. this interest is becoming an international phenomenon known as 'tourism': the use of this leisure time to visit different places, destinations and localities which often (but not exclusively) feature in the holidays and trips people take part in. the world travel and tourism council (wttc) estimate that travel and tourism as economic activities generates around us$ billion, which is expected to grow to us$ billion by . at a global scale, travel and tourism today: why is it a global phenomenon embracing all our lives? tourism supports around million jobs: this is equivalent to per cent of world employment and per cent of world gdp. therefore, the growing international significance of tourism can be explained in many ways. in an introductory text such as this, it is important to stress at the outset the following types of factors and processes in order to illustrate the reasons why tourism assumes an important role not only in our lives but also globally: • tourism is a discretionary activity (people are not required to undertake it as a basic need to survive, unlike consuming food and water) • tourism is of growing economic significance at a global scale, with growth rates in excess of the rate of economic growth for many countries • many governments see tourism as offering new employment opportunities in a growing sector that is focused on service industries and may assist in developing and modernizing the economy • tourism is increasingly becoming associated with quality of life issues as it offers people the opportunity to take a break away from the complexities and stresses of everyday life and work -it provides the context for rest, relaxation and an opportunity to do something different • tourism is becoming seen as a basic right in the developed, westernized industrialized countries and it is enshrined in legislation regarding holiday entitlement -the result is many people associate holiday entitlement with the right to travel on holiday • in some less developed countries, tourism is being advocated as a possible solution to poverty (described as 'pro-poor' tourism) • holidays are a defining feature of non-work for many workers • global travel is becoming more accessible in the developed world for all classes of people with the rise of low-cost airlines and cut-price travel fuelling a new wave of demand for tourism in the new millennium. this is potentially replicating the demand in the s and s for new popular forms of mass tourism. much of that earlier growth was fuelled by access to cheap transport (i.e. the car and air travel) and this provided new leisure opportunities in the western world and more recently in the developing world and newly industrializing countries • consumer spending on discretionary items such as travel and tourism is being perceived as a less costly item in household budgets. it is also much easier to finance tourism with the rapid rise in credit card spending in developed countries, increasing access to travel opportunities and participation in tourism • technology such as the internet has made booking travel-related products easy and placed it within the reach of a new generation of computer-literate consumers who are willing to get rid of much of the traditional ritual of going to a travel agent to book the annual holiday. such technology now opens many possibilities for national and international travel at the click of a computer mouse and to check-in for a flight via a mobile phone. it is evident that tourism is also becoming a powerful process affecting all parts of the globe. it is not only embraced by various people as a new trend, a characteristic or defining feature of people's lives, but is also an activity in which the masses can now partake (subject to their access to discretionary forms of spending). this discretionary activity is part of wider post-war changes in the western society with the rise in disposable income and spending on consumer goods and services. yet tourism is not just a post-war phenomenon as it can be traced back through time as shown in chapter . this highlights how important tourism was in past societies as well as the historical processes of continuity and change which help us to understand tourism development throughout the book. the first major wave of growth in consumer spending was in home ownership, then in car ownership and, then, in accessing tourism and international travel. in fact international travel (and domestic travel, i.e. within a country) is a defining feature of the consumer society. whilst the car has given more people access to tourism and leisure opportunities within their own country, reductions in the price of aeroplane tickets have made international travel and tourism products and services more widely available. for example, the number of air travellers in the uk is expected to rise to million by . this is not without its environmental cost. there is a growing global concern about the ability of the earth's environment and resources to sustain the continued expansion of economic activity, including tourism. whilst scientists have pointed to these concerns since the s, these environmental issues have only really begun to permeate government and people's thinking since the rise of global concerns over climate change and the international kyoto treaty seeking to address greenhouse gas emissions. tourism is the centre stage in these concerns because travel for leisure purposes is not a fundamental necessity, and it contributes to co emissions through the consumption of fossil fuels used to transport people on holiday, at the destination and in the accommodation they use. transportation causes around per cent of the co emissions generated by tourism, with aviation responsible for around per cent of these emissions. improving energy efficiency in transportation may be expected to generate a reduction of per cent in the emissions per passenger kilometre between and . however, the quantity of emissions varies depending on the mode of transport used, with long-haul travel the greatest contributor to highly emissionintense trips. the issue of tourist travel and its global environmental effect through pollution is a thorny issue since tourism is internationally significant and has an important role in society, as we have already seen. there is an almost unanimous reluctance among government policy-makers to directly limit or restrict tourist travel due to its economic effects on destination areas. consequently, many prefer to adopt the politically acceptable and palatable adaptation strategies -seeking to adapt human tourism today: why is it a global phenomenon embracing all our lives? behaviour and destinations to the effects of climate change (see box . ). many people openly admit to being supportive of 'green' and 'sustainable' principles but are unwilling to sacrifice their annual or additional holiday to reduce carbon emissions: likewise, few are willing to sacrifice an overseas destination for a less carbon consumptive and polluting domestic holiday. this assumes a more interesting dimension when one sees some sections of the tourism industry responding to consumer interest in green issues, by offering more 'green' and 'sustainable' holidays, recognizing a business opportunity. critics have labelled this harnessing of green issues as one way of gaining a competitive edge without a complete commitment to implementing sustainability principles in their business practices as 'greenwash' (see table . ). this reflects the fact that tourism in this respect is a phenomenon that is constantly evolving, developing and reformulating itself as a consumer activity. tourism, as a consumer activity, is constantly being developed by the tourism industry and individual businesses, as marketing is used to develop new ideas, products and services and destinations. the challenge for the tourism industry is in adopting new ideas developed in research, such as service dominant logic (see shaw et al., for more detail) which may assist, with the use of social marketing techniques, to adapt human behaviour so that they extend the daily activities which climate change has become a dominant theme in the analysis of the future for small island nations which are little more than a metre above sea level. this has become a major problem for governments when the scale of sea level change is set against natural changes in the land level, which is sinking at a rate of around less than a centimetre per year. however, this means that in less than years some island states such as the maldives may be flooded and therefore uninhabitable. the maldives is a collection of small islands ( of which are inhabited) and it is dependent upon tourism as its main source of external earnings, accounting for over per cent of gdp and almost per cent of foreign earnings' receipts. the dependence upon tourism has meant that the country's international visitors each year are a key source of revenue for the country's economy and should climate change combine with sea level rises to accelerate the pace of change, the country's tourism industry could be completely eradicated. therefore in spite of the country's natural beauty and tourist resorts located across different atolls (i.e. small islands that are just above sea level) its competitiveness as a destination may well be threatened by natural environmental changes. to address these threats, the capital male has built a m sea wall for just one island and other islands in the maldives suffer periodic flooding. despite these major challenges, the country's government is seeking to try and mitigate the worst impacts of climate change, as its resources are very limited and the scale of the problem is huge. it is a story that can be repeated across many similar island archipelagos across the south pacific where climate change may accelerate the pace of sea level rises putting the livelihoods and entire destination in peril for the future. embrace sustainability ideals (e.g. recycling, reuse and minimizing the use of natural resources) to their holiday-taking behaviour. of course, the cynic may argue that the most sustainable form of tourism is none at all if you are serious about your own footprint on the planet. for the tourism sector, they have embraced new ideas (including in some cases sustainability) and pursued strategies focused developing niche products reflecting the way tourism has developed a more specialist focus (see table . ). tourism appeals to the human imagination. as an activity it knows no bounds: it is global and it affects the environment it occurs in, the people who host it, the economies it seeks to benefit and the tourists who consume it as an experience, product and an element of their lives. with tourism having this all-embracing role, it is no surprise that many commentators, researchers and governments have agreed on the need to manage it as a process and activity, especially since it has the potential to snowball and grow out of proportion if it is not managed. therein lies the basic proposition of this book -tourism needs managing if it is to be successful and beneficial rather than a modern-day scourge. tourism and its ability to be sustainable as an activity have been major growth areas of research since the s. the guiding principles of sustainable tourism are based on the management of resources, the environment and economy and society/its culture for the long-term so they are not compromised or damaged by tourism development. a number of key studies exist which provide a very wide ranging overview of the subject's development: krippendorf, j. ( ) the holiday-makers. oxford: butterworth heinemann. this landmark study questioned the necessity of long-haul travel and the impact of tourism including the damage it caused to the environment. this is a complex but critical review of the sustainability debate which challenges current thinking and many of the conventional ideas that tourism can easily be translated into a sustainable activity, particularly in less developed countries. this report outlines many of the principles associated with setting out the principles which can be harnessed to try and make tourism sustainable. yet one of the fundamental problems in seeking to manage tourism is in trying to understand what it is: how it occurs, why it occurs, where it does, the people and environments that are affected by it and why it is a volatile activity that can cease as quick as it can start. these types of questions are what this book seeks to address. it will also look at why tourism as a consumer activity is built on dreams, images and what people like to do; this is notoriously difficult to understand as it involves entering the realms of psychology and the mind of the individual tourist. furthermore, these psychological elements are bound up in notions of enjoyment, feelings, emotions and seemingly intangible and unseen characteristics. the issue is further complicated by the way in which an individual's tastes and interests change throughout their life. in other words, being a tourist is based on the principle of non-work and enjoyment of one's free time in a different locality, and results in an experience, a treasured memory and something personal which develops through our life course. tourism is a dynamic phenomenon and a highly trend-driven activity in a post-modern society where travellers constantly seek new and diverse experiences. this has led the tourism sector to harness marketing techniques to create different products and experiences to very specific market segments based on consumers' interests and values. a range of some of the key trends and developments in recent years are listed below with a brief explanation of their underlying philosophy and examples. slow travel travel to a destination and savouring the journey by not flying, such as taking the train or bicycle so as the rush and stress is taken out of the travel experience so it is slowed down why study tourism? is it just about enjoyment and holidays? tourism and its analysis have become a relatively recent field of study among academics, researchers and commentators. some of the very early student textbooks on tourism (see table . ) can be dated to the early s (although there are examples of other reviews of tourism dating to the s, s and s), with a second wave being produced in the s and then a massive explosion in the late s and s as tourism education and training expanded worldwide. since the s, a wide range of more specialist and niche books have been published on particular aspects of tourism research. there are a range of commonly recognized problems in studying tourism, a number of which are important to the way in which we understand whether it is just about enjoyment and holidaytaking: • tourism is a multidisciplinary subject which means that a wide range of other subjects, such as psychology, geography, economics, to name but a few, examine it and bring to it a range of ideas and methods of studying it. this means that there is no overarching academic agreement on how to approach the study of tourism -it really depends on how you are looking at tourism, and the perspective you adopt which determines the issues you are interested in studying • this has led to a lack of clarity and definition in how to study tourism, something that other researchers have defined as reductionism. what this means is that tourism is normally defined by reducing it (hence 'reductionism') to a simple range of activities or transactions (i.e. what types of holidays do people choose? or how do people purchase those holidays?) rather than by focusing on the framework needed to give a wider perspective or overview of tourism. these problems often compound the way people view tourism as a subject, emphasizing the holiday or enjoyment aspects of travelling (in one's spare time or on business) as the defining features or reference point of tourism. to the general public tourism is something everyone knows about -it is something many have engaged in and so have an opinion on what it is, its effects and widespread development. admittedly, tourism is about pleasure and enjoyment, but its global growth and expansion are now creating serious societal problems and issues; a fundamental understanding of tourism is required if we are to manage and control the impacts and problems it can cause. some critics argue that tourism epitomizes the extreme of post-modern consumption in a society that spends on travel and tourism because it can and not for an intrinsic need for holidays as access to travel is, in relative terms, very cheap and affordable for many. one way of beginning to understand that tourism is more than holidays and enjoyment is to think about why tourism is so important in modern society (i.e. its social, cultural and economic significance) by looking at an important process which has led to the demand for it -the rise of the leisure society. tourism is now widely acknowledged as a social phenomenon, as the nature of society in most advanced developed countries has now changed from one which has traditionally had an economy based on manufacturing and production, to one where the dominant form of employment is services and consumer industries (i.e. those based on producing consumer goods and services). at the same time, many countries have seen the amount of leisure time and paid holiday entitlement for their workers increase in the post-war period so that workers now have the opportunity to engage in the new forms of consumption such as tourism. these changes have been described as being part of what has been termed as the leisure society, a term coined in the s by sociologists. they were examining the future of work and the way in which society was changing, as traditional forms of employment were disappearing and new service-related employment, increased leisure time and new working habits emerged (e.g. flexi-time and part-time work). some commentators described this as a 'leisure shock' in the s since many workers were still not prepared for the rise in leisure time and how to use it. as society has passed from the stage of industrialization to one now described as post-industrial, where new technologies and ways of communicating and working have evolved, sociologists such as baudrillard ( ) in the consumer society: myths and structures, have argued that we have moved from a society where work and production have been replaced by one which leisure and consumption now dominate. this has been reflected in social changes, such as the rise of new middle classes in many developed and developing countries, and these middle classes have a defining feature, which is the concern with leisure lifestyles and the leisure society consumption. the new-found wealth among the growing middle class has been increasingly spent on leisure items and tourism is an element of this (e.g. in , per cent of the population had per cent of wealth; this dropped to per cent in and per cent in in the uk). the international growth in holidaytaking is directly related to this new middle class. the increasing mobility of this group has been reflected in a massive growth globally in their propensity to travel and the growth of a society focused on leisure, of which tourism is prioritized as a key element of their household budgets and as a form of conspicuous consumption as the following statistics suggest: • factors promoting these changes include cheaper air fares and changing patterns of personal expenditure. this snapshot of the uk shows that tourism is a major element of the leisure spending of households and tourist travel to the uk is a major driver of the economy. the growing significance of travel and tourism in the household spending reflects what researchers have described as 'leisure lifestyles'. interest in tourism in europe, north america and other parts of the world has been given an added boost by the impact of new technology such as the internet and the worldwide web, which has rendered knowledge and awareness of tourism and the opportunities to travel worldwide more accessible. the worldwide web has been used as a medium to portray travel options and the product offerings of destinations, so that people can search and explore travel options at a global scale from the ease of a computer terminal. in europe, the impact of this new technology in the early years of the twenty-first century has generated a new tourism boom akin to the rise in international tourism in the s, with new forms of technology and the supply of cheaper forms of travel (i.e. the low-cost airlines) fostering this demand. over per cent of some low cost airline bookings are now made online which illustrates the power of the internet and its role in reaching a new customer base in the tourism sector. this has given rise to the rise of e-tourism, which is the digitization of all elements in the tourism supply chain , whereby the supply and demand for tourism can be met through new virtual forms of distribution such as the worldwide web, as opposed to conventional methods such as travel agents and paper brochures. this has certainly revolutionized tourism and the access to travel knowledge and information, hitherto largely within the confines of travel agents and travel organizers: now everyone can be their own travel agent if they have access to the technology. other commentators have also pointed to the changing sophistication of tourists as consumers, especially the middle classes with their pursuit of authentic and unique experiences. this is part of what pine and gilmore ( ) identified as the experience economy which is the next stage in the evolution of society from a service economy. they argue that businesses need to create experiences which create a sensation, can personalize the experience to build a relationship with the consumer and they suggest four areas of experience that we need to focus on: • entertainment • education • esthetic (i.e. an ability to immerse oneself in something) and • escapism in what is consumed. this has major implications for the types of tourism experience we develop now and in the future and it has gained momentum with the growth of the internet that now allows consumers to seek out these experiences globally. the internet e-tourism is only the first stage of the internet's impact upon tourism. the first wave of internet technology created an online travel community where tourism businesses were able to market and communicate with consumers through electronic media. this has been followed by a new wave of web-based communities known as web . (also described as computergenerated media or social media) where the online content is created by online users and made available to other users via the web . interactive technology. the importance of this technology is that it allows consumers to communicate about social themes such as holidays and travel. so the increasing use of the internet to make bookings and reservations for travel online has been combined with consumer ratings and reviews online through travel sites such as tripadvisor.com. therefore, many of the previous principles of travel planning, where the advice and knowledge of travel agents was seen as a key determinant of holiday decision-making have now been replaced by the technological power of the internet. access to and use of internet technology is increasing and one important feature which many studies confirm is that this technology is increasingly used to search out and peruse travel options as well as for making bookings. with these issues in mind, attention now turns to what is meant by the terms 'tourism', 'tourist' and 'travel'. attempts to define tourism are numerous and very often the terms 'travel' and 'tourism' are used interchangeably. according to the international organization responsible for tourism, the world tourism organization (un-wto): this seemingly straightforward definition has created a great deal of debate. in fact, controversy has surrounded the development of acceptable definitions since the league of nations' attempt to define a tourist in and subsequent attempts by the united nations conference in which considered definitions proposed by the then iuoto (now un-wto). there have also been attempts to clarify what is meant by the term 'visitor' as opposed to 'tourist' and the distinction between tourists who travel within their own country (domestic tourists) and those who travel to other countries (international tourists). what the debates on defining tourism at a technical level show is that it is far from an easy task in agreeing what constitutes a 'tourist'. for example, should we include someone who is a visitor staying in a second home?: they are technically away from their home, but are staying in another form of property they own. similarly, how far away from your home area must you travel before your activity is deemed tourism? a further problem is associated with the category of cruise ship passengers who dock at a port and visit briefly, not staying overnight, or cross-channel trippers who may cross an international boundary but then return within a day and do not stay overnight. to try and encompass many of these anomalies and problems, the un-wto produced guidelines and a useful categorization for defining a tourist, which is shown in figure . . what is increasingly obvious is that new forms of research on tourism are needed to understand how the phenomenon loosely defined as tourism is evolving as it is far from static. for example, research on tourism and migration has identified the short-term migration of the elderly who winter in warmer climatessuch as the uk pensioners who overwinter in the mediterranean -as a new type of tourist. these patterns of tourism migration incorporate owners of second homes, tourists and seasonal visitors who spend two to six months overseas in locations such as tuscany, malta and spain. for example, people own a second home in the uk and tourism is defined as the activities of persons travelling to and staying in places outside their usual environment for not more than one consecutive year for leisure, business and other purposes not related to the exercise of an activity remunerated from within the place visited. the use of this broad concept makes it possible to identify tourism between countries as well as tourism within a country. 'tourism' refers to all activities of visitors, including both 'tourists (overnight visitors)' and 'same-day visitors'. (www.world-tourism.org) have purchased overseas properties. in the usa, estimates of domestic second-home ownership range between . million and . million properties, the majority of which are located in coastal or rural areas. this pattern of seasonal tourism and migration also generates flows of people known as 'visiting friends and relatives', and these are somewhat different to the conventional images of package holidaymakers destined for these locations in europe. in the usa, a long-established trend of a family vacation is the holiday home. some commentators also suggest that existing definitions of tourism are dated and are being challenged by new forms of tourism such as students engaging in a year abroad. therefore, the following definition of tourism might be useful where tourism is in the usa, there is a tendency still to use the term 'travel' when in fact 'tourism' is meant. what is clear is that tourism is associated with three specific issues: • 'the movement of people • a sector of the economy or an industry • a broad system of interacting relationships of people, their needs [sic] to travel outside their communities and services that attempt to respond to these needs by supplying products'. chadwick, ) the field of research on human and business activities associated with one or more aspects of the temporary movement of persons away from their immediate home communities and daily work environments for business, pleasure and personal reasons (chadwick : ) . from this initial starting point, one can begin to explore some of the complex issues in arriving at a working definition of the terms 'tourism' and 'tourist'. probably the most useful work to provide an introduction to tourism as a concept and the relationship with travel is burkart and medlik's ( ) seminal study tourism: past, present and future. this identified the following characteristics associated with tourism: • tourism arises from the movement of people to and their stay in various destinations • there are two elements in all tourism: the journey to the destination and the stay including activities at the destination • the journey and the stay take place outside the normal place of residence and work, so that tourism gives rise to activities that are distinct from those of the resident and working populations of the places through which tourists travel and in which they stay • the movement to destinations is of a temporary, short-term character, with intention to return within a few days, weeks or months • destinations are visited for purposes other than the taking up of permanent residence or of employment remunerated from within the places visited. source: burkart and medlik ( : ) all tourism includes some travel but not all travel is tourism, while the temporary and short-term nature of most tourist trips distinguishes it from migration. but how does tourism fit together -in other words how can we understand the disparate elements? one approach is to look at tourism as an integrated system, which means that one has to ask how tourism is organized and what the defining features are. the most widely used framework is that developed by leiper ( -see hall and page, for a posthumous review of his work) who identified a tourism system as comprising a tourist, a traveller-generating region, tourism destination regions, transit routes for tourists travelling between generating and destination areas, and the travel and tourism industry (e.g. accommodation, transport, the firms and organizations supplying services and products to tourists). this is illustrated in figure . and shows that transport forms an integral part of the tourism system, connecting the tourist-generating and destination regions together. thus, a 'tourism system' is a framework which enables one to understand the overall process of tourist travel from both the supplier and purchaser's perspective (known respectively as 'supply' and 'demand') while identifying the organizations which influence and regulate tourism. it also allows one to understand where the links exist between different elements of tourism, from where the tourist interacts with the travel organizer (travel agent or retailer), the travel provider (airline, or mode of transport), the destination area and tourism sector within the destination. this approach is also helpful for understanding how many elements are assembled by the tourism sector to create an experience of tourism. one major element in this experience of tourism is the tour, which is a feature of holidays and the use of leisure time. the tour, holidays, leisure time and the destination what is evident from leiper's model of the tourism system is that the tour -which is a trip or travel anywhere for pleasure, leisure or businessis a vital element. the tour is an underpinning feature of tourism, a prerequisite for tourism to occur -the consumer has to be brought to the product or experience, and has to travel, and it is a reciprocal event -the traveller travels out and back. transport and single or multiple locations are involved. the conventional definition of touring inevitably implies travel to one or more places, called 'destinations'. a destination typically comprises attractions (e.g. natural and man-made), need to be accessible, have available packages to attract visitors, provide ancillary services such as tour guides and have amenities such as accommodation and retailing. this notion of a destination is increasingly being used as a framework for tourism management by public sector organizations to understand how the visitor experience of a place can be developed and enhanced as well as how the synergies between businesses can be developed and the competitiveness of the destination can be improved. for the tourist, there are various forms of touring: the excursion by road or rail which may have a scenic element known as a touring route; some cruises, where the ship tours a range of destinations or ports of call. conversely, the excursion element may be something that the tourist undertakes at the destination on a day-trip basis or in the form of a more sustained trip, with a planned or unplanned itinerary. whilst the holiday is something which encompasses the entire experience or use of leisure time for a holiday, the tour is a distinct element of the holiday and has distinct travel patterns. these patterns contribute to the development of places as destinations which develop and grow through time. some researchers have attempted to explain the growth, stagnation and decline of tourist resorts such as spas in terms of a resort life cycle. the work of butler, published in , suggested that resorts follow a specific cycle page, ; based on and modified from leiper, ) of growth. the initial exploration by tourists is followed by a period of involvement, often with patronage by a royal figure who started a trend towards visitation (e.g. king george iii visiting weymouth in england) or by its wider popularization as a resort for the elite to visit. this set the stage and created tourism tastes and fashions emulated by the visitors. the next stage of butler's model is development, followed by consolidation and then stagnation. at this point, the resort may decline or action may be taken by agents of development (i.e. an entrepreneur, the public sector or a combination of both) to rejuvenate the resort, and this rejuvenation is the last stage of the model. figure . illustrates this pattern through time and shows the creation (i.e. birth) and decline (i.e. death) of resorts. although such models are highly generalized and simplify the reality of resort development, they are a starting point for the analyses of resorts such as spas through history. the model has also been used in recent years as a basis to try and understand what point specific destinations are in their life cycle, since the model follows the marketing concept of the product life cycle, where products may have definite or indefinite life courses. the same applies to tourist destinations which can decline when tourist tastes and patterns change and so fall out of favour and require a new focus or attraction to bring the visitors back. in view of these issues, which help to understand the nature of tourism as an entity, attention now turns to the scale, significance and importance of tourism as an international activity. once we agree a general definition of what tourism is, we can look for methods that add precision to the scale, volume and significance of tourism as a global activity. measuring tourism also helps to understand some of the problems which planners and decision-makers need to address in butler, ) tourism today: why is it a global phenomenon embracing all our lives? planning for tourism and future growth scenarios. there are three basic considerations in trying to define tourism as an activity, which are: what is the purpose of travel (e.g. business travel, holidaymaking, visits to friends and relatives)? what time dimension is involved in the tourism visit, which requires a minimum and a maximum period of time spent away from the home area and the time spent at the destination? in most cases, this would involve a minimum stay of more than hours away from home and less than a year as a maximum what situations exist where some countries may or may not choose to include travellers, such as cruise passengers, travellers in transit at a particular point of embarkation/departure and excursionists who stay less than hours at a destination, as tourists? there are five main reasons why measuring tourism is important: to understand why and how significant it is for certain destinations, countries and regions in terms of the scale and value of the visitors to understand how important it is for countries in terms of their balance of payments, as it is an invisible export that generates foreign currency and income to assist the tourism industry and governments in planning for and anticipating the type of infrastructure which is required for tourism to grow and prosper to assist in understanding what type of marketing is needed to reach the tourist as a consumer, and what factors will influence tourists to visit a country or destination to help the tourism industry make decisions about what type of action is needed to develop tourism businesses. at a general level, measuring tourism through the collection, analysis and interpretation of statistics is essential to the measurement of the volume, scale, impact and value of tourism at different geographical scales from the global to the country level down to the individual destination. at the simplest level, this is shown in figure . , which demonstrates the trends in global tourism since and forecasts to . part of this turbulence, as glaeßer ( ) notes, is the impact of natural catastrophes on tourism. for example, in the twentieth century there have been natural disasters but between and there have been - such catastrophes each year. these events have periodically interrupted or at worst devastated the tourism industry (e.g. the earthquake that devastated haiti in ), contributing to the notion of turbulence in tourism activity. in other words, a range of factors impact upon visitor arrivals at an international level, because tourism is a very fickle activity (i.e. it is very vulnerable to the external factors mentioned above which act as deterrents to travel) and adverse events can act as shock waves which send ripples across the world and impact upon people's willingness to travel for pleasure reasons. this is because tourism needs relative stability for such activity to occur and the vulnerability to shock effects has been described as volatility in tourism demand which reacts very quickly to these crises or shock events such as wars, currency fluctuations and political instability. tourism also responds to very positive factors such as hosting the olympic games which may lead to a sudden change in the volume of visitors. one of the most recent shock events that have impacted on global tourism is the global credit crunch. whilst this has had different types of impacts on various tourism markets (the most substantial on business travel), its continued existence has led to a global decline in visitor arrivals internationally. in addition, in , the effect of the credit crunch was compounded by the outbreak of a global pandemic associated with swine flu (see figure . ) which initially developed in mexico and spread by travellers returning to their home areas or by visiting new areas so that a number of fatalities occurred in the affected countries as shown in figure , , france, spain, the usa, china, italy, uk and germany • more established destinations in north-western europe and the usa have seen slower growth compared to emerging regions such as africa, n. e. asia, eastern europe, s. e. asia and the middle east. what these rates of growth mean for individual destinations can be seen in web case . which examines vietnam. but one of the enduring problems of tourism statistics are that they are an incomplete source of information because they are often only an estimate of the total pattern of tourism. in addition, such statistics are often dated when they are published because there is a significant time lag in their generation, analysis, presentation and dissemination. this is because many published tourism statistics are derived from sample surveys with the results being weighted or statistically manipulated to derive a measure which is supposedly representative of the real-world situation. hence, many tourism statistics at a country or regional level often state they are estimates of tourism for this reason. in reality, this often means that tourism statistics may be subject to significant errors depending on the size of the sample. the typical problems associated with measuring tourism are as follows: • tourists are a transient and highly mobile population making statistical sampling procedures difficult when trying to ensure statistical accuracy and rigour in methodological terms • interviewing mobile populations such as tourists is often undertaken in a strange environment, typically at ports or points of departure or arrival where there is background noise which may influence responses • other variables such as the weather may affect the responses. source: latham ( ) even where sampling and survey-related problems can be minimized, such tourism statistics have to be treated carefully as they may be influenced by how the tourist was measured and the type of approach used. the main ways of measuring tourists through surveys are as follows: • pre-travel studies of tourists intended travel habits and likely choice of destination (intentional studies) • studies of tourists in transit to provide information on their actual behaviour and plans for the remainder of their holiday or journey (actual and intended studies) • studies of tourists at the destination or at specific tourist attractions and sites, to provide information on their actual behaviour, levels of satisfaction, impacts and future intentions (actual and intended studies) • post-travel studies of tourists on their return journey from their destination or on-site experience, or once they have returned to their place of residence (post-travel measures). such studies can also be used to examine different facets of the tourist as the following three approaches suggest: • measurement of tourist volume, enumerating arrivals, departures and the number of visits and stays • expenditure-based surveys which quantify the value of tourist spending at the destination and during the journey • measurement of the characteristics and features of tourists to construct a profile of the different markets and segments visiting a destination. in the commercial world, tourism data are also collated by organizations that specialize in its collection and analysis including market research companies. tourism consultants may also be commissioned specifically to collect data for feasibility studies of tourism developments or new business opportunities and much of the information remains confidential to the client due to its commercial sensitivity. but in most cases, national governments collate tourism statistics through studies of domestic and international tourism which are then assembled by the un-wto. once we have an understanding of how tourism is measured and collated, then we can begin to think about what the patterns and trends in tourism mean at a global level and what the implications are, particularly in terms of the more critical issues of what forces are affecting tourism as a global activity. new forces affecting tourism -globalization, inequality and the developed and developing world when one looks at the patterns of tourism, and those areas which are growing in terms of international tourism, it is evident that the majority of outbound travellers are from the developed countries of europe and north america, australasia and the new middle class in many developing countries. in some cases, the tourists are travelling to developing countries where the standard of living often means the majority of the population lives at subsistence level or at a much lower standard than the visitor. the contrast in wealth between visitor and host is often very large and it highlights a clear inequality between those who have the disposable income to enjoy the luxury of international and domestic travel and the tourism employees who are working at low wage rates and in low-paid, unskilled jobs. this situation is made worse by the growing impact of globalization. globalization is a process associated with the growth of large international companies and corporations, which control various forms of economic development and production internationally from their host country, making goods and delivering services at a lower cost using low overheads and cheap labour in developing countries. tourism is no exception to this: large multinational hotel chains and tour operators use developing countries and destinations as the basis for their tourist product. in these situations, the economic linkages with the local community are limited, so that low-skill jobs and low economic benefits are traded off against the profits and economic benefits of tourism development being expropriated (i.e. returned) to the country of origin of the multinational firm. in many cases, the weakly developed nature of local economic linkages in developing countries' tourism economies means they are often trapped into such exploitative relationships because they do not have the indigenous capital or entrepreneurs to set up tourism businesses. a lack of education, know-how and power to negotiate with multinationals to new forces affecting tourism maximize the benefits for local people means that tourism can develop as a form of exploitation for such communities. this may mean that rather than importing foodstuffs, such as internationally recognizable brands, to meet the tastes of tourists, local products should be developed to nurture the linkages with the local economy, so local people may benefit. tourists bring their leisure lifestyles with them on holiday and these are increasingly consumptive and conspicuous. their spending power could be harnessed for the benefit of the local economy. a growing problem in many tourism destinations worldwide is that the growth of tourism and expropriation of its profits mean that the environmental resource base which is used to attract tourists (e.g. attractive beaches, wildlife and the cultural and built environment) is not invested in and may be spoilt. more and more, attention is turning to the extent to which tourism is a sustainable economic, social and environmentally based activity. that we should use the environment without conserving it for future generations is one of the central arguments in the sustainable tourism debate. this also raises the issue of inequalities related to tourism; for example, tourist use of local resources required by residents can destroy those resources and environmental quality. this means that local people, governments and international agencies have a responsibility to lobby and take action to ensure that tourism development which occurs in different countries and locations is not only sustainable but seeks to minimize negative impacts as far as possible. it should not marginalize vulnerable groups such as children and the local workforce: the international labour organization (ilo) has estimated that between and per cent of the tourism workforce worldwide comprised children who do not enjoy appropriate standards of labour and employment conditions (see the work of tourism concern at tourismconern.org.uk). among the common human rights abuses which tourism concern have highlighted are: the forced eviction of people to make way for tourism development; environmental damage resulting from tourism which impacts upon the resources people depend upon for their livelihoods; exploitation of tribal people as tourist attractions and poor levels of pay and poor working conditions for employees in the tourism sectors. tourism needs to be developed in an ethical manner so that exploitation is not its hallmark. this is a theme which will be returned to later in the book; at this point it is enough to emphasize that tourism development and activity not only needs to be socially and environmentally responsible, it must be sustainable and long-term rather than short term and exploitative (so that the goose that lays the golden egg is not killed off). the tourism industry needs to work with communities, local bodies and people to ensure that tourism is a win-win activity for everyone and is integrated into the local community rather than just exploiting its local assets. this may require a significant change in emphasis in the way tourism is developed and managed but it is an enduring theme, which is worth highlighting at different points in the book (see box . for more detail). tourists and tourism businesses have a greater responsibility to ensure that tourism is promoted as an activity which will not only enhance global understanding and interaction between people of different cultures and societies, but which will also promote dialogue, benefits and opportunities for the tourist, the host and the environment. so, in some situations, tourism may be a way of providing the stimulus and means for preserving and conserving endangered species and environments as well as providing benefits beyond those, which normally accrue to the tourism industry. tourism has to operate as a profitable activity, but for its long-term future, mutually beneficial relationships and links between the industry, people and the environment must exist to bring financial and sustainable benefits for all and enhance the reputation and image of tourism as a global phenomenon. this is the underlying basis of the pro-poor tourism lobby. in this way the welfare and benefits of tourism to tourists can also be extended to the host population and help to address many of the global inequalities which exist in the growing globalization of tourism activity as multinational enterprises seek to exercise greater control of the choice and nature of tourism being offered to consumers. although this book will not be able to address all of these issues, it is hoped that they will be at the forefront of the reader's mind so that they are aware of the implications of the tourism industry and its activities at a global, national and local level throughout the book. extreme poverty is a major problem for many developing countries who have a large proportion of their population living a subsistence lifestyle, often existing on less than $ a day. at the same time, many of these countries have seen their tourism economies expand as tourists seek new destinations and governments embrace the expansion of this activity to generate foreign revenue. a considerable body of research from consultants and academics has arisen on how this expansion of tourism may be harnessed to address the development problems associated with poverty (see scheyvens, scheyvens, , mitchell and ashley, ). this new thinking has been described as pro-poor tourism which is designed to develop ways to maximize the benefits from tourism to raise local people out of poverty. this involves measures that will: encourage the employment of local people (as opposed to expatriate labour), to provide opportunities for local people to supply goods to tourists and tourism businesses and the creation of micro-enterprises so people can develop their own businesses. however, many obstacles have been identified in implementing pro-poor tourism strategies in less developed countries which include: a lack of awareness and understanding in poorer communities which limits their understanding of the opportunities available; a lack of skills and entrepreneurial talent to capitalize on the opportunities and access to finance to create new businesses focused on tourism as well as cultural concerns over how tourism may affect their way of life. where success stories of pro-poor tourism exist, these examples of best practice need to be shared so that tourism can be harnessed to address abject poverty through case studies of best practice which outline the principles and success factors associated with implementation of such an approach. this is vital if the benefits of tourism development are to be harnessed in the future to address poverty. tourism and management as a focus for the book a framework for the book the title of this book is tourism management and therefore it is useful to present an organizing framework for the book and what is meant by the term 'tourism management'. what is often seen and used as an ambiguous term is the word 'management'. therefore, in this section, the relationship of tourism with management and its meaning in the context of this book is examined. tourism and management as a focus for the book at a very general level, the word 'management' as applied to tourism refers to how tourism needs to be managed as a growing activity at a global, national and local level in order that its often contradictory forces (i.e. the pursuit of profit as a private sector activity and impact on the resource base it uses such as a beautiful coastline on a pacific island) are reconciled and balanced so that tourism develops and is pursued in a sustainable manner. this means there is a need to examine the basic principles associated with the term 'management' and how they can be integrated with tourism as an activity. the basic functions associated with management are: planning, so that goals are set out and the means of achieving the goals are recognized organizing, whereby the work functions are broken down into a series of tasks and linked to some form of structure. these tasks then have to be assigned to individuals leading, which is the method of motivating and influencing staff so that they perform their tasks effectively. this is essential if organizational goals are to be achieved controlling, which is the method by which information is gathered about what has to be done. each of these functions involves decision-making by managers, businesses, tourist destinations or organizations so that they can be harnessed to achieve the objectives and tasks associated with managing tourism. the word 'organization' is often used as an all-embracing term to refer to the type of tourism entity which is involved with tourism as a business or other level. these businesses are motivated by their involvement in tourism to make a profit and, therefore, the efficient organization and management of their activities are essential to ensure that company or organizational objectives are met. there is a school of management thought which argues that management only occurs when chaos occurs and that the function of management is to impose order and structure on that chaos. within organizations dealing with the tourism sector (e.g. travel agents, airlines, tour operators and associated businesses), resources are harnessed (e.g. employees, finance, capital, technology, equipment and knowledge) to provide an output, which in the case of tourism is normally a product or experience consumed by the tourist or service. this output is achieved through the management of the resources. managing tourism demand and supply: the perennial management challenge for tourism organizations one critical element of that management process is related to the way in which businesses have to address the following issues: • what should we produce as a business to meet a certain form of tourism demand? (i.e. should we produce an upmarket high-cost holiday package for ecotourists using tailor-made packages or aim for mass market, low-cost package holidays?) • how should it be produced? (i.e. should we contract in supplies to provide each element of the package product to reduce costs or should we produce each element to ensure quality control and consistency in product delivery?) • when, where and how should we produce the tourism product? (i.e. do we produce an all-year-round or seasonal tourism product?) • what destinations/places should be featured in the tourism experience? • what form of business or businesses do we need to produce the tourism services and products so that we meet demand? tourism businesses need to address these issues for their long-term viability and success or failure will depend upon the management of their organizations' resources to meet demand by consumers in an efficient and profitable manner. it is the concept of supply (i.e. what a business produces) which helps us to understand how the wide range of tourism businesses and organizations (and quite often businesses which do not see themselves as servicing tourists' needs such as taxi companies) combine to link the tourist with the services, experiences and products they seek in a destination. sessa ( ) categorized the supply of tourism services by businesses as follows: • tourism resources, comprising both the natural and human resources of an area • general and tourism infrastructure, which includes the transport and telecommunications infrastructure • receptive facilities, which receive visitors, including accommodation, food and beverage establishments and apartments/condominiums • entertainment and sports facilities, which provide a focus for tourists' activities • tourism reception services, including travel agencies, tourist offices, car hire companies, guides, interpreters and visitor managers. these 'elements of tourism' which combine at a destination highlight the scope of tourism supply, but a number of less tangible elements of supply (i.e. the destination image) also need to be considered. the business environment in which businesses operate can also have a major bearing on tourism supply. for example, in most countries tourism operates within a free market economy, and individual businesses operate in open competition. however, in some countries certain sectors of the tourism industry receive assistance from government through infrastructure provision, marketing and promotional support from tourist boards and other agencies. it is also apparent that when governments decide to promote inbound tourism to destinations (also see further web reading ). the competitive environment which affects tourism businesses and their operation needs to be considered in relation to a number of underlying economic issues: • what competitive market conditions exist for a specific sector of tourism (i.e. the airline sector, hotel sector or attraction sector)? do conditions of monopoly, oligopoly (i.e. where a limited number of suppliers control supply) or other market conditions exist? • how many businesses are involved in these markets? what size are they? are they able to respond quickly to new competitive pressures, or are they characterized by complacency and an inability to redefine their operations in the light of aggressive competition? • do the businesses involved in tourism display patterns of market concentration, where a limited number of businesses dominate all aspects of production (i.e. from retailing through to supply of services and products in the destination such as in the uk tour operator market)? • what are the capital costs of entering a tourism market? are there high entry and exit barriers? for example, starting an airline has high entry and exit costs, requires a high level of technical know-how and large capital investment and ongoing finance to service the business. buying a guesthouse, on the other hand, has low entry costs and no barriers to entry in terms of technical competencies to be able to run and manage it and host visitors • what types of products already exist in the market? is there scope for innovation to develop new products without the risk of 'ambush marketing' by competitors who copy the idea and undercut the competition by loss-leaders to regain market share? aggressive marketing and a limited number of loss-leaders have characterized the low-cost airlines and privatized railways in the uk in an attempt by their owners to capture price-sensitive leisure travellers. in other words, is there scope for price discrimination in the market to differentiate a whole range of products? what these factors indicate is that the market conditions and business environment in which tourism operates are far from static. they are constantly changing, requiring businesses to adapt and to develop strategies to retain their market presence. for tourism businesses, recognizing these evolving patterns, new trends and the need for innovation (i.e. new ideas and products) to address market conditions re-emphasizes the importance of managerial skills in the supply of tourism products and services. this also highlights what mintzberg ( ) identified as the nature of managerial work in organizations -short-term coping, disparate activities and more concerned with brevity, variety and increasing fragmentation. tourism managers and businesses are no exception to this and mintzberg's research has an important bearing on how managers performed certain roles (see table . ) labelled as interpersonal, informational and decisional roles. the ten managerial work roles which mintzberg identified illustrate the scope of activities which operating and managing a tourism business require, as well as some of the complexities of how the individual business interacts with the wider body of interests conveniently labelled the 'tourism industry'. it also suggests how important prevailing market conditions are when they impact upon how a business operates, manages and responds to opportunities, threats and shortcomings in its own organization. yet to do this, a business needs also to understand its relationship to other tourism businesses. a convenient way to explain this is by using the tourism supply chain concept. as tourism is an amalgam of different interests, activities, stakeholders and businesses, the supply chain concept helps us to understand how different interests are functionally linked together to form a distinct method of service delivery. the supply chain concept originates in economics and has been used to explain how different businesses enter into contractual relationships to supply services, products and goods, and how these goods are assembled into products at different points in the supply chain. tourism is well suited to the concept of the supply chain because the product, service or experience that is consumed is assembled and comprises a wide range of suppliers. all too often our knowledge of the supply chain is quite restrictive, since a wide range of components are consumed in tourism including the use of bars, restaurants, handicrafts, food, infrastructure and related services. a schematic diagram of a typical tourism supply chain is shown in figure . . this shows that once the consumer has chosen a destination and product, the decision to purchase involves contacting a tourism retailer (e.g. a retail agent, a direct selling company or an internet-based seller such as www.expedia.co.uk). having chosen a booking medium and selected a package from a tour operator, the package is then assembled. the tour operator enters into contractual relationships with tourism suppliers such as airlines (although larger tour operators may also own their own charter or schedule airline), hotel operators and suppliers of associated services such as airport transfers. these suppliers, in turn, contract suppliers who service their business needs: in-flight caterers, airline leasing companies, airport terminal services (i.e. check-in services, baggage handling, flight controllers, customer service agents for visitors and those with special needs, such as the disabled). with so many organizations involved in the supply chain in relation to tourist spending and activity, it is clear that these are critical break or pressure points where the service provision could potentially fall down (see figure . ) . the business strategies, that travel companies can pursue to develop their supply of tourism services and products include: • focusing on core business (i.e. a holiday company focusing on selling holidays rather than being vertically integrated and operating its own airline and hotels) • seeking to diversify its products. the leading french holiday company club mediterranée (club med), which traditionally sold packages to its holiday resorts, has used this strategy. since and its acquisition of jet tours (france's fourth ranked tour operator, which tourism today: why is it a global phenomenon embracing all our lives? operated to summer and winter locations) it has diversified its operations to sell non-club med packages. rewe in germany has pursued a similar diversification strategy with its acquisition of a wider range of tour operating businesses in the long-and short-haul market • choosing to operate in all segments of the tourism market. tui has adopted this tactic and others such as kuoni are moving towards that goal • non-holiday companies may choose to enter the market: easyjet entered the cruise holiday business in . to implement these business strategies, companies in the tourism industry have adopted marketing-related concepts such as branding to differentiate their products in an increasingly competitive marketplace. for example, club med relaunched its worldwide image to re-emphasize its famous name and association with consumers, and particularly its dominant position in the french market. thomas cook, now owned by the german company c&n touriste, has used its global image and historic association with pioneering tourism to continue its expansion throughout europe (see figures . - . ). there is also a debate among tourism researchers who argue that tourism is a unique sector in that it displays characteristics of partial industrialization which are explained more fully by leiper ( : ) where only certain organizations providing goods and services directly to tourists are in the tourism industry. the proportion of (a) goods and services stemming from that industry to (b) total goods and services used by tourists can be termed the index of industrialization, theoretically ranging from per cent (wholly industrialized) to zero (tourists present and spending money, but no tourism industry). what leiper's approach to the tourism sector shows is that managing the broad phenomenon called 'tourism' is complex for a number of reasons: • the tourism industry is not a homogenous sector or segment of the economy: it is made up of various organizations directly involved in tourism (i.e. those which directly service tourist needs) and those indirectly involved and so may be described as allied industries (i.e. food suppliers, retailers and other service providers) • some of the organizations directly involved in tourism are responsible for encouraging and promoting tourism development and marketing • the allied industries do not always see themselves as tourism-related enterprises • the destination or area which the tourists visit is not the sole responsibility of one business or group of businesses; usually the public sector intervenes to ensure that business objectives (i.e. profit and increasing tourism numbers and revenue) are balanced with local needs and business interests (known as 'stakeholder interests') in relation to the resource base which tourism utilizes (i.e. beaches, attractions, the infrastructure and overall environment) • the public sector is responsible for trying to liaise, plan and manage these diverse group of interests that are associated with tourism as a phenomenon as well as having an underlying responsibility in many cases for the marketing and promotion of the destination. therefore, one can see how complex the management of tourism is when the interests and variety of organizations involved in tourism are considered and then the concept of partial industrialization is introduced. from this discussion, who is responsible for tourism management can be examined at a number of levels, although this is not an exclusive list but a range of illustrations: • at the individual business level, the manager(s) is (are) involved with the functioning and running of the enterprise • at the destination level, responsibility often lies with a public sector led agency such as a tourism department (either as a stand-alone body or as part of a local authority department). in extreme situations where a destination is deluged with tourists due to its popularity, the public sector may lead with a public-private sector partnership involving business interests to manage the visitors on the ground • at the country level, it is the national tourism organizations, funded by the public sector through taxes and sometimes with private sector members, who promote and market the country as a place to visit and attempt to manage the diverse interests involved in tourism • at each level, be it the individual business, destination or country, a complex web of interactions and interrelationships exist which need to be taken into account in the decisions, interests and actions taken to manage tourism. in each of these illustrations, the functions of management are harnessed. tourism management as a pursuit, however, is further complicated in that there is a great debate as to what tourism is, what needs to be managed and who should be responsible. the fact that tourism can be seen as an experience based on the pursuit of pleasure and profit raises many complex issues such as whether the tourist is consuming a product, experience or service, and it leads to many debates on what to manage and how far management controls should be exercised by the tourism industry and public sector. so how does this book address these questions? one way is to view the managerial process of tourism as a multilayered process, in which the various organizations and stakeholders involved in tourism engage at different levels through time. figure . demonstrates this. the focus begins with the individual business and the management processes (controlling, planning, leading and organizing) are continuous through the interconnected stakeholder groups from the individual business through to the various interests known as the tourism industry. these interests and the connections between management at different levels and between groups mean that, in reality, these groups also have to be aware of external factors that will impact upon management such as the visitor, the business environment, consumer trends, the growth of the leisure society and political processes affecting tourism at government level. the book is organized in such a way that these issues are explained in a manner where the links between different elements of the tourism sector are addressed through examples and case studies. each chapter builds upon the one preceding to develop the knowledge and understanding of what the tourism industry is, the management challenges facing each sector and how tourism affects changes in different contexts. accommodating, anticipating and responding to that level of change is among the major challenges for tourism management in the new millennium. englishmen at rest and play the tourist movement the englishman's holiday the travel trade tourism, principles and practice tourism volumes - : sage library of tourism and hospitality management the consumer society: myths and structures tourism, past present and future the concept of the tourist area cycle of evolution: implications for the evolution of resources (eds) travel, tourism and hospitality research: a handbook for managers and researchers crisis management in the tourism industry the contribution of neil leiper to tourism studies the statistical measurement of tourism tourism systems: an interdisciplinary perspective the nature of managerial work tourism and poverty reduction: pathways to prosperity the experience economy exploring the tourism-poverty nexus tourism and poverty elements of tourism. rome: catal aspects of service dominant logic and its implications for tourism management further reading questions why is tourism such an important activity in the twenty-first century? how would you classify tourists? why is tourism management important for a business operating in the tourism sector? how stable is tourism as an economic activity? key: cord- - j yq authors: storbacka, kaj; moser, ted title: the changing role of marketing: transformed propositions, processes and partnerships date: - - journal: ams rev doi: . /s - - - sha: doc_id: cord_uid: j yq nan digitalization affects every aspect of a firm's business modelfrom front-end to back-office, from how firms create value for their customers to how they capture value-and doing so can reshape every facet of the firm. by adapting their business models to the possibilities of technology, firms are facing an accelerating transformation of their activities, offering new opportunities for "out-of-the-box" development of new processes and tools, which effectively challenge deeply engrained functional silo-based thinking. despite the ubiquity of digital transformation, much academic research still seems to take a functional view (verhoef et al. ) , where information systems look into the development and adoption of specific technologies (nambisan et al. ) or analytics schemes (davenport and ronanki ) , strategic management research focuses on understanding the role of new digitalized business models (foss and saebi ) , and marketing research focuses on what is generally called "digital marketing" or the development of an omnichannel environment (verhoef et al. ; lamberton and stephen ; kannan and li ) . lately, some researchers have argued for multi-, cross-, and/or trans-disciplinary approaches to digital transformation (kumar ; crittenden and peterson ; verhoef et al. ; grewal et al. ) . instead of digitalizing existing practices within silos, we need new ways to cross-fertilize the insights from different functional development streams into a coherent firm-wide approach. staying in the functional silos may, for instance, lead to ignoring relevant opportunities for new work divisions between the functions. this view of digital transformation challenges many of the fundamental theories and concepts that management and marketing have been built on. this drives us to evaluate, for instance, how economies of scale work, if transaction costs can be used to define firm boundaries, how we define markets, and how to measure value (storbacka ) . consequently, marketing scholarship actively questions the boundaries of marketing and calls have been made for the need to engage in research that actively removes the blinders of the "mainstream assumptions, theories and methods" (moorman et al. , p. ) , with the aim to uncover new ways to look at value creation in the market. practitioners are facing this dilemma in real time. this interview with ted moser, who advises firms on the digital transformation of marketing, aims at identifying "boundarybreaking" ideas that can form the basis for new types of research questions. ted holds an mba in marketing and strategy from the wharton business school. he has years of experience advising leading firms on growth strategies that cascade from business model innovation to go-to-market transformation. his work spans markets in digital, medical, and industrial technology, plus financial services and media entertainment. ted has lived and worked in the us, europe, and latin america, and has worked extensively in asia. ted is a senior partner in the san francisco office of prophet, a strategic brand and marketing consultancy with offices around the world. prophet helps leading companies digitally shift their innovation, marketing, and branding to achieve transformative growth. ted began his consulting career at corporate decisions, a growth strategy specialist spun off from bain and co. and led their european practice. after corporate decisions was sold to mercer management consulting, ted led mercer's us west coast practice and chaired its global service offer innovation committee prior to joining prophet. ted has contributed to several books on business model innovation, for instance, profit patterns, which he co-authored with adrian slywotzky (slywotzky et al. ). presently he is writing a book about the transformation of marketing, rooted in the ripple effects of digital innovation, and this is the focus of our discussion. storbacka: when i talk to marketing practitioners, they are very focused on digital marketing. however, it seems that you are taking a broader view on how digitalization affects marketing-a view that takes us way beyond digital marketing? moser: the digital transformation of marketing includes digital marketing, but it reshapes much more, encompassing the "digital ripple effect". if we examine the question of how digital is changing the role of marketing and the ways marketing is getting done, we end up with a transformation agenda that far exceeds the normally accepted definitions of digital marketing. to illustrate, let's start with the business innovations that marketing is asked to support. when a marketing leadership team plans for the next one to three years, the first question asked should be: "how is our firm's business portfolio changing in search of higher value, and how can marketing support the success of that change?" most often, digital is changing what the business is trying to do. firms may be developing new business models or offers that are altered fundamentally by digital. consequently, marketing is likely to find itself marketing things that it never marketed before. that's just one example of how digital has a ripple effect on marketing, without touching what we typically call digital marketing. another example is the way customer expectations and behaviors are evolving due to digital innovation. marketing leaders need to re-assess more frequently how buyers are evolving the way they gather information, come to decisions, prioritize benefits, and experience value throughout the customer journey. the digital ripple effect means marketing needs new and better customer evolution sensing systems. in parallel, digital is creating an explosion of new channels and related new tactics. we take for granted the existence of websites, mobile sites, and branded apps but these are all innovations in the last years. on the rise now are marketing through a digital assistant, an ar/vr application, geolocation beacon data, iot streaming data dashboards, and in-product ai chat. all this means that marketing teams need to learn to use new channels that they've never used before. most fundamentally, thanks to digital the whole scope of marketing is changing. the touch points that marketing has with the buyer are clearly becoming digital and, in that context, we do find digital marketing. however, i would argue that even this is not marketing with the same borders that it used to have. what we call digital marketing is increasingly becoming digital selling. what is selling? it's a one-to-one relationship between a vendor and a customer. a relationship where the two sides are getting to know each other, and as they do, the vendor is reading the clues that the customer provides, to provide a personalized message, personalized advice, and a personalized value proposition. that's the classic role of a sales rep-to establish a one-onone advisory relationship that provides contextualized value. so, digital changes marketing by turning marketers into virtual early-stage sellers far upstream in the funnel. going forward marketing will create that one-on-one relationship with the buyer long before the sales rep does downstream. this matters because in some product categories, with some customer segments, marketing can keep selling virtually all the way through the point-of-sale. buyers may no longer see value in speaking to a human being before they choose. at that point, marketing is encroaching not only on selling but on e-commerce and sometimes customer success. it's not simply taking the dynamics of what we've traditionally called marketing and turning that digital. all of this means that the role that marketing can play in a company's success is changing. it can go beyond creating reputation for the company, to creating relationships and even revenue. early adopters of digital approaches were only on the hook for impressionsmimicking a traditional marketing role -but they're increasingly on the hook for engagement and leads and going forward may be asked for quarterly revenues and a lower total cost of sales-to-revenue ratio. over time the cultural ethos of marketing will shift beyond creating a digital version of today's marketing culture. it will evolve toward a culture of digital dialog with customers instead of one-way communication to them, plus a culture of resultsgeneration for the company. with greater visibility into marketing's impact on the customer, resources will be allocated toward these relatively new capabilities. marketing leadership's challenge will be to help a new ethos rise, while still nurturing marketing's spirit of creative experiential communications. the final consequence of these changes is the need to redefine the kind of talent marketing needs to attract, recruit and keep. not only those who understand digital marketing technically, but those who can thrive in the type of environment that the digital ripple effect creates. i hope this illustrates how profound of a transformation is coming to marketing, one that includes but also far surpasses what we call digital marketing, spanning the entire digital effect. storbacka: this is obviously the reason why you call for the transformation of marketing. my understanding is that you have divided the transformation into three different types. could give an overview? moser: yes, let's discuss three types of transformations: transformed propositions, transformed processes and transformed partnerships. in each of these three areas i will highlight four major trends, so a dozen trends in total. i hope your readers find at least some of these worthy of future research. (see fig. ) thanks to the nature of digital offer innovation, marketing leaders will need to enable their product and solution marketing teams to excel at an evolved playbook. how to integrate improved flow-workflows in a b b context and lifeflows in a b c context-into value propositions as a new type of benefit layered over traditional benefit categories? how to become known as the critical intelligence within the flow? how to market past the point of sale to encourage the customer behavioral change needed to experience the value of new flow throughout the usage lifecycle? how to win over trusted influencers who will back up the company's value proposition claims? let's discuss these in more detail. in a digital world, the innovations to be marketed are increasingly systems that promise new benefits of flow. in business markets we call these better workflows. in consumer markets we might call them better lifeflows. digital innovations carry the potential for profiling and quantifying the before-and-after value of flow improvement. to do so will require a new level of customer centricity and insight. what helps products and services to become flow-enabling systems is three-fold. first, sensor-rich offerings-whether a cell phone app, a connected product, an ip-addressed sensing component, or a visible cloud-hosted keystroke-are connecting the product/service to the customer as the customer uses that product/service in their daily lives, generating key data needed to profile their broader activity flow. second, programmable software is controlling what was once considered hardware functionality-and can further log detailed product use. this software-controls-hardware logic will continue to expand over time, including extension to smart materials. to support lifecycle usage flexibility and customer data insight, physical product lines are also being transformed into a one "base" with many "bits," whether those are called razors and blades, coffee makers and pods, power tool platforms and end pieces, even car chassis and replaceable outer shells. third, the customer's use of digital payment methods (credit and loyalty cards, smart phones) is creating a forensic history of economic activity. innovations will be most effectively marketed in the context of b b customer workflow and b c customer lifeflow benefits. yet flow-improvements are not something that most marketing teams are accustomed to bringing out. marketing teams are instead used to promoting static product and solution benefits. to market flow benefits effectively, product and solution marketing will need to much better understand how the customer uses what it is they have purchased. the new responsibility that will fall on marketing is wide-reaching. we see flow benefit communications emerging. i'll share two widely recognized examples. when starbucks markets coffee to me it's no longer just about great beans and flavors; it's about the lifeflow of ordering on the smart phone as i'm leaving home and picking up with no wait and no pay as i continue to work. the genius of apple advertising has been to convert what used to be product ads into seconds consumer lifeflow movies based on what its products enable. flow benefits don't replace product or service benefits; they can add a new and often differentiated layer of benefits on top. in b b one might think of total workflow benefits as a modern successor to 'total cost of ownership'. it's how a new system enables better flow that compresses time, improves customer productivity, and enables innovative outcomes. similarly, when marketing to a consumer, it's how the new system enables better flow that saves time, makes loved ones happier, creates amazing experiences, or helps advance a career. companies who don't make or control an entire system can make the mistake of thinking they're not part of a flow. in fact, they are. they're just part of a multi-brand system that the customer has stitched together. in this situation, marketing should be advocating the creation and curation of virtual system options through partnerships and apis. flow marketing principles will then increasingly apply. somewhere in each work-and lifeflow there is, or there will be, intelligent decision-making that adds particularly high value to the customer, brought about by software code and aided by machine learning (ml) and artificial intelligence (ai). as flow benefits are marketed, different companies may claim to be the brains behind that intelligent flow. this claim matters because flow intelligence will emerge over time as a customer priority and a competitive differentiator. in parallel, intelligence is becoming a powerful new brand attribute that distinguishes modern brands from old ones. beyond learning to market flow, it is additionally strategic for marketing to decide whether and how the company can credibly claim that it provides the brainpower within the flow. marketers should aim to win credit for valuable flow intelligence and extend that credit strategically through brand architecture. competition will be fierce-both direct and substitute competitors will make claims. the winner of this contest will differentiate today and will hold the high ground heading into a wave of business innovation that lies still further ahead of us-autonomous business. this trend raises questions around an intelligence brand. on the one hand a dedicated intelligence brand can focus the spotlight on a company's intelligence value added. on the other hand, it can deposition the master brand. by focusing so intently on how intelligent watson is, ibm may have made its flagship brand seem less so. microsoft made different choices, distributing certain types of intelligence responsibilities across several product, platform, and master brands. a key question for all marketers to wrestle with is: "how do we differentiate on intelligence while ensuring that intelligence equities enhance the brands we care about most?" the branding of intelligence is a deep topic in its own right, and one that we won't do justice to in this interview. one illustrative example, tied to designing for branded intelligence: it's best to enable the brand's value to visually be performed through algorithmic action and expression, rather than just be represented through static symbols. this can reveal the intelligence brand's essential value, psychology, and ethics. the sale is just the start customers will purchase digital innovations with best intentions of achieving new flow benefits. yet it's not guaranteed that their experience will be positive; they may or may not succeed. in a pre-digital world, the customer's experience of quality was primarily dependent on product or service performance. in a flow world, a great customer benefit experience depends meaningfully on the customer's own behavioral change-a blend of user engagement and know-how-making lifecycle marketing critical. that's why marketing needs to view the sale as the starting line, not the finish line, for the company's value proposition. the implication: marketing should allocate resources to enable customer flow success at key points throughout the usage lifecycle. the achievement of customer success will do more than raise customer satisfaction scores; it will lead to accelerated growth. many innovations will be priced as subscriptions or variable utilities vs. once-and-done purchases, putting the customer in a mindset of expecting ongoing value delivery experiences in return for ongoing payment. in this context customer success will raise retention. going further, lifecycle marketing will enable the company to achieve a trusted understanding of the objectives driving customer usage, leading to improved customer cross-sell, upsell, and advocacy. as more becomes trackable, customer activities and experiences throughout the usage lifecycle will become more visible-given customer consent, of course. transformed marketing in a data privacy era will work hard to gain customer consent to data visibility because it is key to creating a winwin lifecycle customer relationship. companies are now designing services that offer the customer valuable services in exchange for data access. it will fall on modern marketing to support the design, management, and/or promotion of these value-for-data exchanges. this activity may require marketing to collaborate with other lifecycle programs that go by a variety of names: customer experience, customer success, customer engagement, customer loyalty, renewal marketing, customer marketing, etc. at the end of the day it means that the second half of the infinity loop of the customer's journey-the usage and owner experience half-\will require as much skill and focus as marketing has traditionally reserved for the consideration and selection first half of the journey. transformed marketers will ensure that the customer hears of a company's value propositions not just from the company, but from influencers as well. the appeal of a value proposition has never been limited to just differentiated claims; it has also been enhanced by differentiated communicators of those claims-think of celebrity endorsers. transformed marketing will work to systematically influence the messages that those influencers provide. in a digital distribution world, digital influencers are replacing the expert advisory role that traditional distributors provided as part of their service. modern value propositions might be delivered most persuasively by influencers who organically surround the buyer, separate from company-sponsored campaigns. influencer advice used to be bundled with a distribution service model; now that distribution is going direct, independent digital influencer voices are emerging, sometimes through media-based business models. it's up to marketing to get to know them intimately. thanks to the digital datasphere, companies can begin to tackle the question of who influences whom. those firms that think their customers aren't part of an influence cascade probably haven't thought long enough or hard enough about the question. while in some markets the influencer concept is leading to opaque or corrupted influencer networks, in most markets the question is more about deploying resources to win over influencers. a growth area in transformed marketing will be to better map complex influence chain dynamics with increasing clarity, and by doing so learn to invest in, if not formally manage, the influencers that deliver best results. storbacka: this comes across as a major shiftbasically challenging many of the foundations for marketing. this must have multiple implications for how marketing works in the future. moser: yes, exactly! but there is more. digital does not just transform the value propositions that a company markets. it also transforms the processes by which marketing is done. marketing leaders will guide the transformation of the core marketing process from digital as alternative marketing to digital as default marketing. to succeed, this process shift must also shift culture: from one of long-prepared broadcast message delivery to one that seeks to listen and understand the customer before responding in a personal manner, drawing on intelligent content that is supported by dynamic segmentation, and equipping marketing to engage in an individualized relationship and journey with each prospect and customer. this newfound capability will enable marketing to travel further with the customer into territory traditionally owned by sales (which may in parallel be working its way into marketing's territory through its own digital transformation). the resulting mandate will call for effective trust building, bridge process development, and data integration between the marketing and sales functions. what emerges will be a new core marketing process-let me provide more detail. until recently, digital has been the alternative way to market: there was mainstream marketing and digital marketing. what's new is that digital is becoming the default way to market. we are on the verge of digital marketing becoming just plain marketing, with other marketing becoming the exception. this is already visible: cmo surveys show that more than % of all marketing spend, from ads to headcount to technology, is now focused on digital channels. it's driven by customers, whose time spent on digital media properties has only grown, and whose behavioral demographics indicate it will only grow further. only the inertia of marketing's past will for a few more years keep the 'digital' modifier in front of marketing-it's no longer needed. the biggest shock delivered by the emergence of digitalas-default marketing is not a technical shock, although we all know there is a universe of new concepts, technologies, and techniques to learn. the biggest shock is a shock of very human proportions. marketers need, at a human level, to shift from being one-way communicators, who are obsessed with their message, to two-way relationship builders who are obsessed with customer dialog, including listening hard to interpret what the customer is trying to say. it's important to be clear about what new capabilities digital is and isn't giving marketers. digital is not giving marketers a mouthpiece or a forum to speak. marketers have had a mouthpiece since the printing press and have been using it to put advertising in newspapers (since ) and magazines ( ) for centuries. marketers were given an even more powerful mouthpiece through telecommunications and have been using advertising through radio ( ) and tv ( ) for decades. while marketers have always had a mouth and a public square to speak in, digital technology is giving marketers ears to listen, a mind to process what it hears, the ability to say something in return, and a private room in which to carry out customer dialog. it's equipping the marketer for conversation. the inbound customer might speak first; marketing needs to listen hard to understand why the customer began speaking before saying something back. the outbound company might speak first; marketing needs to listen carefully to understand what part of its message was relevant and worth speaking further about. this frames why the biggest process transformation challenge of digital-as-default marketing is a cultural challenge. now, in the blink of an eye-counting in marketing yearsmarketing is being called upon to become good at listening, good at clarifying what the customer meant to say, and good at building an authentic human relationship in the intimacy of a private room. this sets up the second marketing process transformation challenge. when digital becomes the default process for marketing, content becomes the new bottleneck to marketing impact. this is because creative content teams are set up to prepare the carefully planned one-way speeches that marketers have historically been delivering. now the creative content team needs to support marketing's new capability to have a private room customer dialog, where every word that marketing says depends on what it heard, and how it interpreted what its dialog partner-the customer-wants to hear. when technically implemented, digital marketing provides a request to the content team using 'if/then' algorithms that supports a simple line of reasoning: "if this is the customer who i think it is, and if they're trying to accomplish what i think they're trying to accomplish, then here's what content would further develop our relationship. i need to share this content in this channel format with this message in order to move our relational and commercial journey forward". the reason content becomes the new bottleneck is that it is a lot easier for digital marketers to learn to program if/then statements, which explode the amount of customized content that is needed, than it is for the marketing content department to produce all that content. the more sophisticated the if/then rules get, the greater the bottleneck becomes. how can the creative content team produce enough of the right content to support the aspirational customer relationship development represented by those if/then rules? at the same time, how can marketers spot declining return on customization to know when to stop? the answer is intelligent content. intelligently structured and intelligently applied, modularly built and machinelearning assembled content can provide the content agility that is required by the demands of private-room customer dialog. with intelligent content, marketing can carry out its transformed process of building strong customer relationships rooted in dialog and understanding, one customer at a time. this is easier said than done. content departments need to rethink their mission, core processes, technology platforms, and skillsets. they need to ask themselves, 'how do we reimagine content packages for a digital world?"; and "how do we use automated intelligence to reshape content modules into unique combinations, allowing ml/ai to begin to create the content itself?" companies in regulated industries (healthcare, financial services) have an additional roadblock: "how do we gain regulatory approval of modular content blocks rather than as monolithic outputs, and gain pre-approval for appropriate combinations of modular content?" a key enabler of digital-default marketing and agile content is a third transformed process-the development and application of dynamic segmentation schemes. in an analogue world, companies and their marketing teams needed company-wide agreement on a segmentation scheme; "our four personas" or "our eight segments". everything that marketing and product management did ideally conformed with that segmentation. this was a critical and positive marketing impact driver. it enabled marketing to move beyond communicating the company's message in the middle of the public square to the entire public audience, and instead enabled marketing to divide the audience into groups, sending each group to a corner of the public square for delivery of more targeted messages. dynamic segmentation takes this one step further to pose a challenging question: "how can changes in the process of segmentation help marketers evolve from speaking one-way to groups in the corner of the public square to carrying out private room dialogs with one customer at a time?" the technical answer is to unpack the multi-factorial analysis that produced a company's standard segmentation scheme in the first place. behind every quality traditional segmentation scheme lies some form of cluster and factor analysis that incorporates multiple customer dimensions. despite the valuable contribution these schemes have played historically, going forward they can stand in the way of the more granular and dynamic segmentation needed to deliver private customer dialog. what digital makes possible is to store single-factor segmentation dimensions in a purer and simpler form, and then combine them later when a specific customer segmentation is needed. this implies a larger number of more narrow segmentation schemes available in a system that can be combined throughout the customer journey to serve as the best segmentation expression at a specific point in time, for a specific type of customer. here is a helpful analogy drawn from an unlikely placeyour local bar. if you want to order a whiskey, your first decision is to choose either a blended whisky-made by a master blender in the factory lab who has pre-blended multiple varieties to achieve a dependable, enjoyable taste-or choose from a range of single malt whiskeys, each providing a distinct territorial expression. imagine that the master blender now stops by the bar and offers you a third choice: line up several single malts across the table and, given the taste experience you are seeking that night, he would micro-blend a unique combination to match the moment. multi-factorial segments are blended whiskeys; dynamic segmentation schemes are the blend-for-the-moment third choice. a key success factor in implementing any segmentation scheme digitally is marketing's ability to reliably recognize and assign segmentation values for a specific customer. there are two challenges worth mentioning. one is that early in the relationship development process the customer is often not well known. deciding on the optimal way to speak to a customer who is not known well enough to be segmented can be tricky. one leading security software company whose product came pre-bundled with new computers found that a large percentage of new computer owners de-installed its software within hours of turning their machines on. when studying how to curb this unwanted behavior, it found two very different customer segments: sophisticated it users who were offended that the pc company was trying to make a security software choice for them, and unsophisticated it users who didn't think they needed security software at all. it had strong but different arguments to make to each group but that hinged on its ability to recognize and classify a customer accurately into the right segment. in the meantime, and to literally buy time, what should be said to the unknown customer based on probabilities? a second challenge arises from the fact that only some of the customer characteristics that matter in dynamic segmentation are permanent. some temporary dimensions involve what stage of a pre-purchase journey the customer is in, with what level of engagement. other temporary dimensions involve where the customer is in a given workflow or lifeflow, assuming that marketing has visibility into the ownership stage of the lifecycle. the above overview highlights the three key aspects of dynamic segmentation. first, the blend of segmentation schemes that are deployed at a given moment in the customer's journey will change. second, some of permanent customer characteristics will change from unknown to known or from wrongly guessed to correctly confirmed as customer knowledge rises. finally, temporary customer characteristics that capture contextual customer states will fluctuate. the result is a much more powerful approach to segmentation than the monolithic segmentation of the past. despite its challenges, a change in the process of segmentation can be a significant enabler of overall marketing impact. a wide group of stakeholders both in and out of marketing need to get together, agree on the business opportunity logic behind new segmentation, and then align on dynamic segmentation architecture. the last transformed process, already implied earlier in the interview, is that marketing-sales bridge processes must be built. in a digital-default marketing world, both marketing and sales may know the same customer, have siloed data on the same customer, and have different tactics in mind for that same customer. the starting point is usually a messy one, requiring basic hygiene. sales and marketing might have a crm record in salesforce.com, and a different record in marketo. if customer names are listed differently or if they're not the same customer id, progress starts by fixing the basics. if notes from the sales call didn't get back to marketo, or if information about what the customer did on the website is not known to the sales force, then there's a next-level problem to solve. once mechanics are fixed, the real upside work begins. regular marketing reports should highlight accounts that deserve sales prioritization; self-service portals should exist for sellers showing which topics and marketing assets are being reviewed by which prospective buyers. most important, marketing and sales will need to be able to speak to the customer with one coordinated voice. this will become particularly important as digital marketing extends into traditionally selling territory, and as digital selling teams similarly move upstream into what was regarded as marketing's turf. only by working together can the process of moving an individualized customer relationship through the sales funnel come to a satisfying ending. storbacka: am i right to suggest that the process changes that you describe call for marketing to step out of its organizational silo, or at least work more closely with many other functions? moser: at a minimum, marketing needs to integrate in new ways and negotiate collaborative governance at new handshake points with sales and with postpurchase customer success. but there are additional types of silo spanning to consider. this is what my third transformation category covers. the digital ripple effect on marketing, described so far as transformed propositions delivered through transformed processes, also demands and enables several types of transformed partnerships. marketing leaders need to forge new partnerships with stakeholders both outside and inside the walls of corporate marketing. first, marketing needs to create two-way sharing of customer journey insights not only with sales, but also with its priority channel partner marketers, making best-practice data sharing a new condition for top-tier partnership. simultaneously, corporate needs to redefine the kind of value-added that it expects of geographic marketing as traditional sources of value are falling and new sources of value rise. within the marketing team, performance management software tools are enabling leaders to more effectively partner to shift resource allocation logic away from siloed activity levels, toward integrated strategic objectives that better align with business growth strategy and impact. finally, marketing analytics leaders must pursue embed-and-extend partnerships with a wide range of marketing stakeholders to create a pervasive performance culture. the first partnership transformation centers on why marketing should incorporate two-way data sharing into the design of its channel partner programs. channel partners may be physical and e-commerce retailers in b c markets; they may be brokers, resellers, e-commerce, and value-added resellers, service providers, systems integrators, or independent software vendors in b b markets. corporate marketing teams are using digital marketing to reach past channel intermediaries and establish increasingly direct end-consumer relationships. some end-customers are responding, creating a three-way company/channel/customer data flow. this can raise practical problems. both company marketing and channel partner marketing can end up with the data equivalent of one hand over one eye. each will see one part of the customer's journey, one portion of the customer's activities, and will as a result draw an incomplete or inaccurate view of how the customer is behaving, leading them to make less than best moves in advancing the customer's relational and commercial journey. digital marketing will be most successful if company marketers and its priority channel partner marketers gain full visibility by sharing end-customer insights. this is similar to how digital marketing shares endcustomer relationships with the sales force, but with more constraints given legal and competitive complexity. some of the same 'fix-the-basics' to-do list that we prescribed for marketing-sales bridge processes applies to channel partners as well. where channel partnerships are unique is in the design of channel partner programs. traditional channel programs exist in a tiered manner-platinum, gold, silver-based on company dollar volume sold by the partner, with potential added incentives around co-op advertising levels, rank-order in channel partner recommendations, and achievement of certain product mix targets. transformed marketing adds a new partnership angle: intensive data sharing as a new condition for top-tier partnership, and basic data sharing for any level of partnership. whether that literally takes the form of data or of cookie sharing-again compliant with data regulations-the core principle is to enable the customer to experience seamless coordination while improving channel partner and company results thanks to shared visibility. whether a company can execute on this transformation depends on the attitude and strength of its channel partners. if partners are opposed to data partnerships and are stronger in the value chain than the company they distribute, then not much will happen. however, if key channel partners are like minded or are significantly weaker than the company they distribute, real change can occur. channel relationships are adjacent to a second key partnership that is being transformed-that between corporate headquarters marketing and geographically-based marketing. because headquarters is a funding 'hub' and geographies are recipient 'spokes', geographies constantly carry the burden of proof for their value added. the value of geographic marketing in a digital era is more a story of "shift" than one of rise or fall. thanks to digital, the value-added of geographic marketing to headquarters is evolving, with traditional sources of value falling and new sources of value rising. digital is directly or indirectly hollowing out traditional sources of local marketing value added. language translation software is increasingly accurate, lowering local language value added. product homogenization, a result of income segment convergence-meaning that we see more middle class in developing countries, more polarization in rich countrieshas helped standardize product lines, lowering product diversity value added. the emergence of a global customer culture in some parts of the market lessens the value of local team insight. finally, the rising capabilities of remote teams via videoconferencing is lessening the need for many feet on the ground. at the same time, digital is directly or indirectly creating new sources of local marketing value added. the emergence of mega markets rivalling the us, such as china, the eu and india, may justify more dedicated investment. the proliferation of micro-cultures, developed in parallel to-and in response to-global culture, re-introduce a new form of local insight value. the rise of account based marketing (abm) draws on local data sources and regulations plus decision maker insight sourced from local sales teams. and finally, the necessity to digitally collaborate more closely with channel partners, leads marketing to need talent in the field. the challenge and opportunity for geographic managers is to use technology to diminish costs where digital erodes employee value added, then invest in new skills that create new value. the final two transformed partnerships are inter-related, as were the first two. these next two partnerships address digital's impact on marketing resource allocation. digital technology-in the form of marketing performance management (mpm) software-is enabling marketers to shift their approach to return on marketing investment (romi) resource allocation and measurement. this shift is welcome and needed, because it moves marketing leaders away from an often-dangerous marketing-activity romi approach toward a healthier growth strategy-marketing objectives-marketing activities romi approach. in doing so, modern mpm creates the possibility of a transformed partnership among marketing leaders to allocate marketing resources for optimal business impact. the origins of mpm trace to advertising, where marketers first spent large sums. it then expanded to other marketing activities, an intuitive extension as each activity mapped to an accounting line item budget. one can argue that this turn of events did more harm than good. given that some activities had short-term, quantifiable benefits, while other activities had long-term, hard-to-quantify benefits, this activity-based romi approach led marketers to an imbalanced focus on unit volume acceleration through short-term incentives while failing to maintain high equity assets that drive a differentiation premium. this triggered an important analytical response-the treatment of brand as a financial asset with tangible balance sheet value through a more sophisticated, quantitative and timelagged model that gave brand managers a voice in romi debates. these models remain critical for supporting highlevel "brand v. demand" allocation considerations; however, they don't substitute for operational marketing resource optimization. enter mpm software. marketing leadership teams can use mpm tools -supplemented by program portfolio governance, program design and funding processes, outcomes analytics, and agile program managementto partner together for business impact romi. mpm tools are still immature, having been originally designed for narrower use. nonetheless they can enable marketing to plan and track at a unit of investment-the integrated marketing program (imp)-that directly supports a company growth goal. each imp branches into marketing objectives, and each objective branches further to multiple marketing activities. through tagging, mpm tools become a large 'pivot table' converting imp objectives into multi-activity game plans with draws on accounting budgets. during planning mpm becomes a real-time iterative translator between strategy, activity, and finance. an mpm information structure can enable resource allocation based on efficacy in achieving business goals and marketing objectives, using outcome oriented kpis. management can vet and improve the quality and fit of a team's marketing strategy and tactics in addition to the basket of activities that they choose. activity resourcing can be optimized in context, informed by that activity's effectiveness in meeting the specific company business goal. this final partnership transformation discussion will share some parallels with the resource allocation partnership just discussed. a transformed marketing function will require multiple forms of analytical support, addressing a wide range of structured to unstructured issues, in order to bring about widespread use of analytics. marketing analytics was born in an advertising and brand building era. in the past decade, its scope has exploded in sync with marketing's growing demand generation role and the astronomical growth of customer and marketing data. most analytics teams are stretched for resources, with a backlog of varying requests that make support a challenge to prioritize. in this context marketing analytics can pursue an embedand-extend partnership agenda with a wide range of marketing stakeholders to support pervasive romi capabilities. it's helpful for the analytics team to structure analytics support around three delivery formats. each format requires a different type of partnership with different marketing stakeholders for effectiveness. the first support format is to partner with tool users, with a goal of empowering them to do their own analytics using functionality embedded in their platforms. every martech tool has embedded analytics. most focus on measuring returns on that platform's data set, tied to its activities. such a perspective is helpful to tool users but not relevant to the outcomesoriented questions of senior marketing executives. the support goal of the analytics team should be to highly leverage its time supporting these stakeholders-user tool groups is a good example-in order to free time for less-structured, higher-value analytics support. the second support format helps each integrated marketing program (imp) leader to structure, implement, and apply the right analytics framework for their particular imp. this will require a custom approach per imp, likely using a data lake; over time patterns will emerge where similar imps can benefit from similar analytical approaches. one key to success is to structure analytics for each key imp objective, not just the overall imp, so that key program elements can be evaluated instead of delivering all-or-nothing imp assessments. the third support format is the least structured. it involves partnering with the marketing leadership team to structure and answer an ongoing series of hypotheses and questions that leadership would like to explore to improve marketing's effectiveness. keys to success include maintaining a pipeline of valuable questions, prioritizing those questions continuously, and bringing back answers that are action oriented. how much of a transformation this represents for analytics will depend on each company's starting point. transformation may involve a shift from brand to demand analytics. it may involve a shift from light, reactive support to a systematic and strategic support. a team whose support is structured in the way we've discussed will enable the use of analytics to become a pervasive and informative force throughout marketing. how do you make the transformation happen? storbacka: the transformations that you describe are comprehensive, complicated and challenging, and are likely to take quite a long time to implement. even contemplating the implementation of the changes will make any marketing executive exhausted. how companies are approaching this challenge? moser: focus is key. leaders should choose the few trends that matter to them most, not tackle them all. given that principle, we see two types of change happening, cmo-led and ceo-led. when the cmo leads change, he or she typically develops a proactive marketing transformation agenda that sets out a vision for how to modernize the marketing function. the agenda is unique to each company, consisting of three to six impact areas over several years where "from…to" transformation is critical. these multiple changes ladder up to a coherent theme that the cmo develops, articulating a value proposition for the future role of marketing in the company. armed with this vision, the cmo asks the ceo/c-suite for transformation funding, because most marketing organizations are funded to carry business-as-usual operations, not to reinvent. the transformation typically lasts two to three years, with annual accountability for what transformation has been accomplished and what business impact has been produced. i've found that most cmo's have the desire to do this. the only question is whether that desire rises from a "do it someday" to a "do it now." we see certain patterns in the triggers that compel cmos to act: new-in-role cmos may believe that starting strong is key to making their mark; cmos may want to prepare a game plan ahead of the arrival of a new ceo; cmos may decide that one year's annual plan will be transformation vs. incremental; an enterprise-wide digital transformation initiative may reach marketing; and/or marketing may plan for a shift concurrent with a major business shift (often m&a). a cmo-led marketing transformation agenda is the best opportunity for marketing to step forward in playing a more strategic role within the company. cmo's have a markedly different chance to frame the discussion if they have led the thinking. that's why it's good to act with urgency, because there is another scenario for transformation that is less promising-a ceo or coo-led transformation. the ceo may approach the transformation from one of several angles. the ceo often sponsors enterprise-wide digital transformation, including marketing. in that scenario marketing will be competing with other functions making similar transformation requests, often with a cost cutting promise that attracts capital more easily than marketing's promise of better growth. in a second scenario the ceo may want to build direct-toconsumer business. in this case the ceo may either expand marketing's role or may shrink it-in the latter case bringing in a new chief revenue officer or chief monetization officer and cutting marketing out. in a third scenario, the ceo makes a judgment call about where the marketing function ends, and the sales function begins-especially if there is tension between the two. there are two "grey zone" areas that get a lot of attention, the first being: who does digital nurture in the marketing qualified lead (mql)-sales qualified lead (sql)-proposal stages. the second area relates to who handles inside sales/remote sales, which at first glance appears to be a sales function, but which is increasingly being supported by best-move decision rules and content rooted in digital marketing infrastructure. the ceo may also create an executive vice president of marketing and sales role and make that executive responsible for working out the grey zone as it shifts between sales and marketing over time. in the final scenario, the ceo appoints a new executive to do one or more things that a modern marketing function might do, but isn't judged as capable of leading. the most common responsibility carve-outs are around data (chief data officer), digital (chief digital officer), experience (chief experience officer) or customer (chief customer officer). in each carveout the role of marketing shrinks somewhat. you'll notice that there is a massive choice point here. either the cmo proactively creates a transformation agenda to move the company forward, and through that agenda moves marketing's role forward within the company-or the ceo/ coo proactively creates a transformation agenda and typically reduces marketing's role in the company's future. this is why it is critical for cmos to get ahead of the transformation of marketing. the multi-faceted transformation that ted moser is talking about points to numerous needs and opportunities for marketing scholarship to change-both when it comes to research and teaching. one key question is whether universities are preparing our students for this "new normal" by properly educating them. for academic research to provide insight into the transformation-and the related capability and management issuesresearch should focus on the less mature areas of the change. this may be counter-intuitive for many scholars, considering the risk averse journal review processes that regularly stamp out innovation (moorman et al. ). but at the same time, i believe that the time is right for more bold explorations of the boundaries of marketing. there are obvious needs to understand more about how the new digital tools can be integrated into marketing processes. in addition to these, i would like to highlight three both academically and managerially important topics. first, taking work-and lifeflows as a starting point for understanding value creation changes many dominant mainstream marketing perspectives. it is important, however, to understand that these flows are not the same as "customer journeys". they entail several customer-journey parts (with many different providers) but the flows are larger and much more complex (c.f. hamilton and price ). as digitalization makes resources more liquid, organizations and individuals have access to an extensive variety of market and nonmarket resources that they can integrate into their work-and lifeflows. the key to these flows is to understand what the organizations or individuals are trying to achieve-what are their goals? a provider that helps them achieve their goals is involved in value creation, whereas providers that make it more difficult for them to achieve goals essentially destroy value. in marketing scholarly language this relates to a need for more research related to the formation of "use-value" or "value-in-context" (vargo and lusch ) , and research on what marketing strategy and marketing management processes look like, if they take their starting point in the work-and lifeflows. second, and as a consequence of the above, marketing needs to look beyond the seller-buyer dyad, to see the dyad as part of a larger network or system of stakeholders who contribute to the creation of value (hillebrand et al. ; nenonen et al. ) . this systemic view implies that the locus of value creation moves beyond the borders of the firm, i.e., the value emerging in the work-and lifeflows is cocreated with a multitude of stakeholders, not only by the firm and for the customer (tantalo and priem ) . therefore, marketing needs to free itself from the mainstream "firmbased and value-capture-centric view" and move towards a "system-based and value-creation-centric view" (amit and han ) . in a systemic view, revenue development alone cannot be used to measure the success of marketing and sales. hence, to support future marketing management new measurements are needed. finally, in this systemic worldview, there are several important issues related to work divisions and boundaries, both between functions inside organizations and between various stakeholders in the marketplace. working together with influencers and channel partners to better support the workand lifeflows of customers entails many challenging and interesting research questions related both to the sharing of data and to the sharing of successes (and failures). and, as noted in the interview, marketing and sales are becoming more integrated-a development that has been accelerated by the covid- developments. further research is needed to better understand how an integrated marketing and sales function should operate, and what new capabilities firms need to develop. funding open access funding provided by hanken school of economics. open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article's creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article's creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/by/ . /. value creation through novel resource configurations in a digitally enabled world digital disruption: the transdisciplinary future of marketing education artificial intelligence for the real world fifteen years of research on business model innovation: how far have we come, and where should we go the future of technology and marketing: a multidisciplinary perspective consumer journeys: developing consumer-based strategy stakeholder marketing: theoretical foundations and required capabilities digital marketing: a framework, review and research agenda transformative marketing: the next years a thematic exploration of digital, social media, and mobile marketing: research evolution from to and an agenda for future inquiry challenging the boundaries of marketing digital innovation management: reinventing innovation management research in a digital world capabilities for market-shaping: triggering and facilitating increased value creation profit patterns: ways to anticipate and profit from strategic forces reshaping your business extending service-dominant logic -outside marketing and inside managerial practice value creation through stakeholder synergy service-dominant logic digital transformation: a multidisciplinary reflection and research agenda from multi-channel retailing to omni-channel retailing: introduction to the special issue on multi-channel retailing publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -ltp iv z authors: wilson, nick; baker, michael; crampton, peter; mansoor, osman title: the potential impact of the next influenza pandemic on a national primary care medical workforce date: - - journal: hum resour health doi: . / - - - sha: doc_id: cord_uid: ltp iv z background: another influenza pandemic is all but inevitable. we estimated its potential impact on the primary care medical workforce in new zealand, so that planning could mitigate the disruption from the pandemic and similar challenges. methods: the model in the "fluaid" software (centers for disease control and prevention, cdc, atlanta) was applied to the new zealand primary care medical workforce (i.e., general practitioners). results: at its peak (week ) the pandemic would lead to . % to . % loss of medical work time, using conservative baseline assumptions. most workdays ( %) would be lost due to illness, followed by hospitalisation ( %), and then premature death ( %). inputs for a "more severe" scenario included greater health effects and time spent caring for sick relatives. for this scenario, % of medical workdays would be lost in the peak week, and % over a more compressed six-week period of the first pandemic wave. as with the base case, most ( %) of lost workdays would be due to illness, followed by caring for others ( %), hospitalisation ( %), and then premature death ( %). conclusion: preparedness planning for future influenza pandemics must consider the impact on this medical workforce and incorporate strategies to minimise this impact, including infection control measures, well-designed protocols, and improved health sector surge capacity. inputs for a "more severe" scenario included greater health effects and time spent caring for sick relatives. for this scenario, % of medical workdays would be lost in the peak week, and % over a more compressed six-week period of the first pandemic wave. as with the base case, most ( %) of lost workdays would be due to illness, followed by caring for others ( %), hospitalisation ( %), and then premature death ( %). preparedness planning for future influenza pandemics must consider the impact on this medical workforce and incorporate strategies to minimise this impact, including infection control measures, well-designed protocols, and improved health sector surge capacity. it is probably only a matter of time before the next influenza pandemic. the only uncertainties are its timing and impact. effective planning for public health interventions before and during a pandemic is likely to reduce its impact [ ] . a pandemic is likely to be extremely disruptive, particularly for the health sector. not only will there be a surge in demand for health services (preventive as well as cura-tive), but the health workforce is likely to have higher exposure and incidence rates. we estimated for the impact of pandemic influenza on the primary care medical workforce (i.e., general practitioners) for a single country -new zealand. the estimates inform planning for the pandemic as well as for other new emerging infectious disease threats, including those from bioterrorism, by providing some estimates for the level of "surge capacity" that must be built into the health sector. new zealand has approximately health practitioners plus around support workers delivering services in the community [ ] . around % of its medical practitioners and % of its nurses work in primary care settings. the population to general practitioner (gp) ratio varies considerably across different territorial authorities from about to about [ ] . new zealand's primary health care strategy [ ] , released in , places primary care at the centre of the country's health system. it defines a future for primary care where, increasingly, primary care and public health strategies are expected to be coordinated and intermeshed, with the overall objective of improving population health and reducing health inequalities. the strategy led to the formation of new non-profit umbrella organisations, called primary health organisations (phos) [ ] . phos are responsible for ensuring that their constituent general practices and community organisations provide comprehensive, continuing and coordinated care to their enrolled populations, including health promotion and prevention programmes. increasingly, phos are held accountable to their funders for a range of population health outcomes. the development of phos mirrors, to an extent, the development over the past five years of primary care groups and trusts in the united kingdom [ ] . the united states centers for disease control and prevention (cdc) have developed a relatively simple deterministic model, "fluaid" (on freely available software), for analysing the impact of future influenza pandemics [ ] . the output of the model is the number of deaths, hospitalisations, and illnesses requiring medical consultations for a wave of pandemic influenza. these outputs were used to estimate lost workdays in this analysis. the model assumes that no public health interventions (e.g., limitations of movement, vaccine, or antiviral drugs) are used to control disease spread. specific details on the fluaid software and the various assumptions in the model are detailed on the cdc website [ ] and other documents [ , ] . this model has been used in other studies [ ] [ ] [ ] . the default values used in fluaid were used for the mortality rates, the hospitalisation rates and the rates of illness. the default values for the incidence rates of clinical illness were also used (i.e., % and % for "most likely" results). working doctors are likely to be in better health than the general population (the "healthy worker effect"), and have fewer risk factors associated with severe sequelae from influenza infection. for example, they are probably far less likely to have chronic respiratory disease, since they have markedly lower smoking rates in new zealand than the rest of the population [ ] . therefore, the proportion of doctors assumed to be in the "high-risk" category was arbitrarily halved (i.e., from . % for - year-olds down to . %). this may be overly conservative, but we wished to systematically err towards underestimating the impact of a pandemic on this workforce in the baseline model. the length of time associated with hospitalisation (average of eight days) and from clinical illness (two days) was based on the united states data in a previously published model [ ] . in addition to this, it was assumed that there would be one day of convalescence for clinical illness and three days convalescence after hospitalisation (i.e., before returning to work). to determine the working days lost, these figures were adjusted by the proportion of a typical week that is spent at work (i.e., five out of seven days). the latest available national figure for the total number of registered medical practitioners working in primary care was (i.e., those working four or more hours per week in and who are classified as working in "general practice" or "primary care") [ ] . the average hours worked per week by these doctors is hours, and it was assumed that they would work full time during the pandemic period (unless affected by illness). the fluaid model does not consider the time frame of the pandemic within an affected region. the length of influenza epidemics is highly variable [ , ] . for the baseline analysis the distribution of cases and a duration of eight weeks was used, based on the results of a stochastically simulated influenza pandemic [ ] . for this scenario the pandemic wave was assumed to last only six weeks and the upper range "maximum" values from the fluaid model were used (for the % incidence rate scenario). the proportion of cases in the peak week was raised to % (from . %), the upper limit of the days of hospitalisation was used ( days [ ] ), and days lost from illness was doubled relative to the baseline model (i.e., to four days). in addition, it was assumed that every doctor would spend an average of . days during the pandemic wave period caring for sick relatives or household members. baseline assumptions result in to lost workdays for % and % incidence rates respectively ( table ) . the lost work time was . % to . % of maximal capacity at the time of estimated peak pandemic impact (week ). an estimated % of lost workdays arose from illness not requiring hospitalisation, % from hospitalised cases, and % from deaths caused by influenza (when using the % incidence rate). the "more severe" model inputs resulted in lost workdays (table ) , with a loss of . % of maximal capacity in the peak week and . % over the six-week period. the lost workdays mainly arose from the impact of illness not requiring hospitalisation ( %), then the time spent caring for others ( %), the impact of hospitalisation ( %), and then the impact of premature death ( %). the model results suggest a substantial impact on general practitioners, even with very conservative assumptions. for the "more severe" scenario a mortality rate of per is predicted (albeit for just one pandemic wave). this is much less than the total population rate for the pandemic in new zealand of per [ ] , but it is more than united states total population rates for the asian flu pandemic ( per ) and the hong kong flu pandemic ( per ) [ ] . the results suggest that the major contributor to lost workdays will be episodes of uncomplicated illness that do not require hospitalisation. if time spent caring for sick relatives is considered (i.e., as in the "more severe" scenario) then this also made a substantial contribution to the total workdays lost. the impact of lost workdays will be magnified by the increased demand on the medical workforce, as has recently been modelled for primary care consultations and hospitalisations in new zealand [ ] , and for critical care services in both new zealand and australia [ ] . there are several broad strategies to reduce the impact of an influenza pandemic on health care workers. first, infection control strategies aimed at doctors need to be in place. these measures include basic hygiene practices and also mask use may be appropriate (depending on risk [ ] ). health authorities and doctors themselves could also stockpile and then use antivirals at the appropriate time. such stockpiling has already commenced at a national level in new zealand and various other countries [ ] . recent modelling work indicates that access to enough antivirals could substantially reduce the number of clinical cases and hospitalisations in the population [ ] . second, pandemic planning needs to include specific measures to maintain the functional capacity of health care workers, bearing in mind that the impact of an influenza pandemic is likely to vary between urban and rural areas. while exposure to infection may be less in relatively isolated rural areas, such areas generally have far less "spare" health care capacity, should gps be incapacitated. general practices and health authorities can consider plans to provide care for the ill dependents of their medical staff so as to reduce absenteeism rates. through other pandemic planning activities they can also potentially reduce the overall impact of a pandemic and hence demands on their staff. for example, rapid action at the start of the pandemic to cancel elective procedures could enhance workforce capacity. establishing dedicated primary care assessment centres for patients with suspected influenza could also reduce overall gp workload. third, strategies are needed to manage the psychological impact of pandemic influenza on health care workers. surveys of such workers show that they report a lower willingness to report for duty for infectious diseases epidemics (sars, smallpox) than for most other forms of catastrophic disasters (environmental disasters, mass casualty incidents) [ ] . experience with sars also dem-onstrated the psychological importance of having welldesigned policies and protocols in place. even in situations where health care workers perceive themselves to be at increased risk, they report feeling reassured by simple protective measures based on sound epidemiological principles, when implemented in a timely manner [ ] . a review of the foundations for a sars preparedness and response plan has specifically highlighted the importance of both appropriate staffing and support [ ] . fourth, improving health sector surge capacity now would be desirable as the new zealand health sector is often running at stretched capacity (e.g., especially emergency departments [ ] ). expanding existing services such as the "healthline" (a free telephone information service to the public staffed by nurses) may also be worthwhile. similarly, active promotion of key websites with information on managing influenza (e.g., as per the cdc website [ ] ) could be publicised each winter season. all such measures would benefit the public prior to a pandemic as well as potentially reducing the demands on the medical workforce in the primary care and secondary care settings during a pandemic. finally, a greater focus on the primary care nursing workforce would be of benefit. following the implementation of the primary health care strategy there has been a rapid shift to capitation funding of general practices, and an attendant increased focus on team-based primary care (principally gps and practice nurses). this trend raises the possibility of increasing substitution of gp work roles by nurses. this type of substitution has occurred for a decade or more in a range of community-governed non-profit practices and other capitation-funded practices [ , ] . a recent review of the medical workforce in new zealand also highlights the potential efficiencies from some role shifting from doctors to other health workers [ ] . expanding such a non-medical health workforce, while also vulnerable to the infection during a pandemic, would provide a buffer for the gp workforce in the event of attrition of gp capacity. the uncertainties associated with pandemic influenza mean that estimating its future impact is problematic. this model could substantially underestimate the true impact because the new strain may be particularly infectious and/or virulent, and the incidence rate for clinical illness might be higher for doctors given their likely occupational risk [ ] . for example, one review of nosocomial outbreaks reported a health care worker incidence rate to be as high as % [ ] . furthermore, doctors may be relatively slow to seek care for themselves -especially at the time of a national crisis when their professional obligations are greatest. other parameters used in the modelling may also have been overly conservative, such as the extent of the healthy worker effect among doctors and the amount of time off work taken to care for sick relatives (which was zero in the baseline model and fairly small at . days in the "more severe" scenario). there was also no consideration in the model of absenteeism effects from fear of infection (e.g., in the case of particularly virulent strains). indeed, this absenteeism effect could be more important than actual disease in reducing health sector capacity. although we consider that the baseline results are more likely to underestimate than to overestimate the impact of a future influenza pandemic, there are still plausible reasons why they could be overestimates. these include the following: • various international and national public health interventions (as recommended by who [ ] ) may reduce the impact of pandemic influenza; • at least for subsequent pandemic waves, an appropriate vaccine may be available; • antivirals could prevent infection and reduce morbidity amongst the medical workforce and the rest of the population [ ] ; • improved treatment could lower hospitalisation and mortality rates (relative to the figures used in this model). this modelling could be further refined to address some of the limitations detailed above. clarifying the prevalence of "high-risk" conditions among the medical workforce would be a particularly important refinement along with improving the estimates of time off work to care for relatives (or even absenteeism from fear of infection). expanding such modelling to other parts of the health sector workforce is also desirable, along with exploring the extent that such research is generalisable to other threats (e.g., from other new emerging infectious threats, including those from bioterrorism). this modelling work has a number of limitations and so these results could still substantially overestimate or underestimate the impact of the next influenza pandemic on the primary care medical workforce. nevertheless, this modelling work highlights the importance of infection control strategies for health care workers, pandemic planning, and improving current health sector surge capacity. world health organization: who consultation on priority public health interventions before and during an influenza pandemic world health organization . health workforce advisory committee: the new zealand health workforce, framing future directions, discussion document population need and geographical access to general practitioners in rural new zealand the primary health care strategy reducing health disparities through primary care reform: the new zealand experiment organization and financing of british primary care groups and trusts: observations through the prism of us managed care fluaid . : a manual to aid state and local-level public health officials plan, prepare and practice for the next influenza pandemic (beta test version) nationalvaccine program office): fluaid the economic impact of pandemic influenza in the united states: priorities for intervention modeling the economic impact of pandemic influenza in the united states: implications for setting priorities for intervention pandemic influenza planning: using the u.s. centers for disease control fluaid software for small area estimation in the canadian context estimating the impact of the next influenza pandemic on population health and health sector capacity in new zealand modeling the impact of pandemic influenza on pacific islands cigarette smoking by new zealand doctors and nurses: results from the population census medical council of new zealand: the new zealand medical workforce in medical council of new zealand human resources for health flunet as a tool for global monitoring of influenza on the web the mathematical modelling of influenza epidemics containing pandemic influenza with antiviral agents the influenza epidemic in emerging infections: pandemic influenza. epidemiol rev pandemic influenza-implications for critical care resources in australia and new zealand pandemic influenza: global update. science potential impact of antiviral use during influenza pandemic health care workers' ability and willingness to report to duty during catastrophic disasters risk perception and impact of severe acute respiratory syndrome (sars) on work and personal lives of healthcare workers in singapore: what can we learn? foundations of the severe acute respiratory syndrome preparedness and response plan for healthcare facilities emergency department overcrowding -can we fix it? cdc: influenza (flu): what to do if you get sick: overview (interim guidance) primary care teams: new zealand's experience with community-governed non-profit primary care third sector primary care for vulnerable populations health workforce advisory committee: fit for purpose and for practice: a review of the medical workforce in new zealand health workforce advisory committee . sepkowitz ka: occupationally acquired infections in health care workers. part i transmission of influenza: implications for control in health care settings preliminary aspects of this work were funded in part by the new zealand ministry of health, but the views presented in this final article do not necessarily represent ministry of health policy. we thank the reviewers alan hampson and lance jennings for their helpful comments on the draft. the author(s) declare that they have no competing interests. all authors contributed to the writing and nw, mb and om also contributed to the design. nw conducted the analyses. all authors read and approved the final manuscript. key: cord- -enmtckpe authors: tuckel, peter s.; milczarski, william title: the changing epidemiology of dog bite injuries in the united states, – date: - - journal: inj epidemiol doi: . /s - - -y sha: doc_id: cord_uid: enmtckpe background: in , the most recent year for which data are available, dog bites ranked as the th leading cause of nonfatal emergency department visits in the united states. as dog ownership spirals upwards in the united states, it is important to continue to monitor the epidemiology of dog bite injuries. this study provides contemporary data on the incidence of dog bites injuries in the united states and in new york and profiles individuals who have been treated for dog bites in emergency departments. the study also examines the demographic correlates of the rate of injuries at the neighborhood level in new york city and maps the rate in each neighborhood. methods: at the national level, the study examines longitudinal data on dog bite injuries from to gathered by the centers for disease control and prevention. for new york, the study analyzes data for – collected by the new york state department of health. a negative binomial regression analysis was performed on the state data to measure the simultaneous effects of demographic variables on the incidence of dog-related injuries. a thematically shaded map of the rate of dog bite injuries in new york city’s neighborhoods was created to identify neighborhoods with higher-than-average concentration of injuries. results: in both the united states and new york the rate of dog-bite injuries increased from to and then underwent a significant decline. injuries due to dog bites, however, still remain a sizable public health problem. injuries are more prevalent among school-age children, inhabitants of less-densely populated areas, and residents of poorer neighborhoods. in new york city, poorer neighborhoods are also associated with fewer dogs being spayed or neutered. conclusions: to reduce the rate of dog bite injuries, prevention programs – particularly those which center on teaching the dangers of canine interactions with humans – should be targeted at children. dog bite injuries tend to be clustered in identifiable neighborhoods. dog bite prevention programs and stricter enforcement of dog laws can target these neighborhoods. while the appellation attached to dogs is "man's best friend," dog bite injuries are a common occurrence. data covering the years - revealed that approximately . million individuals in the united states were bitten by dogs each year (gilchrist et al. ) . of these, % necessitated medical attention. between and , there were an average of , visits to emergency departments (eds) per year for dog bites (loder ) . in , almost , individuals required reconstructive surgery owing to dog bites (american society of plastic surgeons ). the morbidity associated with dog bites is particularly pronounced among children. one study estimates that approximately one-half of all children aged and younger have been bitten by a dog (beck and jones ) . of nine causes of injury resulting from activities children frequently engage in (e.g., baseball, playground accidents, etc.), dog bites rank second in terms of annual visits to an ed (u.s. product safety commission ) . most dog bite injuries in the us are inflicted by owned pet animals and not strays. three of five bite victims were bitten by the family dog or one living in the neighborhood (overall and love ) . significantly, the number of dogs in the united states has steadily increased over the last two decades. in , approximately million dogs were owned as pets in the united states. by , the number of dogs had climbed to . million (appa ). the total population of the united states in numbered million. in terms of household penetration, . million households ( . %) now own a dog (insurance information institute ). as the number of dogs has spiraled upwards, both the demographics of dog owners and the characteristics of the dogs themselves have undergone a noticeable change. during the past decade, the rates of dog ownership have risen sharply among older adults, hispanics, and residents of large metropolitan areas. correspondingly, there has been a decrease of dog ownership among families with young children (marketresearch.com ). the share of dogs which are smaller (weigh under pounds) has increased as well in this time span and this trend is expected to continue (petfoodindustry.com ) . with the growth in the ownership of dogs in the united states and the shift in the characteristics of both owners and dogs, it is important to continue to monitor the epidemiology of dog injuries and implications for public health. this study has five objectives: ( ) to provide contemporary data on the incidence of dog bites in the united states and in new york, ( ) to furnish a detailed profile of individuals who have been treated for dog bites in new york to describe individuals who are most at risk, ( ) to present the socio-demographic correlates of the rate of dog bite injuries at the neighborhood level in new york city which can help to identify the characteristics of neighborhoods with a higher incidence of dog bite injuries, ( ) to map the incidence of dog bite injuries at the local level which can be used to target neighborhoods which have a disproportionately large number of dog bite injuries, and ( ) to provide data on the changing composition of the dog-owning population to help explain the epidemiological findings. the analyses conducted in this study rest principally on data collected from ed visits in the united states and new york. the national-level data are derived from the web-based injury statistics query and reporting system (wisqars) (centers for disease control and prevention ). wisqars is an online, interactive database which provides national estimates of both fatal and nonfatal injuries. the present study utilizes the nonfatal injury data which comes from the national electronic injury surveillance system-all injury program (neiss-aip), sponsored by the u.s. consumer product safety commission and the cdc's national center on injury prevention and control. the neiss-aip is based on a sample of hospitals randomly selected from all hospitals in the united states which have a -h ed and a minimum of six beds. the sample is stratified by hospital size measured in terms of the number of ed visits each year. the nonfatal injury data provide estimates of injuries treated in eds by cause of injury (e.g., dog bites), race/ethnicity, gender, and disposition of the patient after being released from the ed. in addition to the wisqars database, this study examines individual-level patient records from new york. these patient records include a large number of demographic, diagnostic, and treatment variables. the patient records also include more detailed information concerning the racial and ethnic characteristics of patients than is contained in the national data sets. importantly, the new york patient records include geographic identifiers such as the county or the -digit zip code in which the patient resides. the data for new york come from the statewide planning and research cooperative system (sparcs), which is under the auspices of the new york state department of health ( ). sparcs assembles data on outpatient, inpatient, and ambulatory surgery patients treated in all hospitals in new york state. this study also draws upon data gathered by new york city's department of health and mental hygiene (dohmh) ( ). the database consists of dog bites which are reported via online, fax, or phone to the city's dohmh animal bite unit. each record in the database provides information on: ( ) the date of the bite, ( ) the breed, age, and gender or the dog, ( ) whether the dog was spayed or neutered, and ( ) the zip code and borough of the person who was bitten. altogether, there were , records spanning the years from to . this tally clearly underrepresents the incidence of dog bite injuries in the city. the comparable number of dog bite injuries which were treated in eds in the city during the period to totaled , . most likely, this disparity was because individuals who were bitten both had to know to contact and take the initiative to contact dohmh. it should be noted, too, that the breed of the dog was missing on . % of the cases and the zip code of the person who was bitten was missing on % of the cases. injury code. for both the national and state data sets, identification of patients who were treated for a dog bite was based on two separate injury codes. the international classification of diseases, ninth revision (icd- ) external cause of injury code (e-code) e . -dog bitewas utilized for the years prior to . both the icd- e-code e . and the icd- cm e-code w . xxa -bitten by dog (initial encounter)were utilized for the year . just the icd- cm e-code w . xxa was used for the years - . sociodemographic characteristics. both the wisqars and sparcs data sets furnished information about the age and gender of patients. the sparcs data sets also included two separate variables about the race and ethnicity of patients. a typology was created from these two variables with the following five values: "white, non-hispanic," "black, non-hispanic," "asian, non-hispanic," "other, non-hispanic," and "hispanic." importantly, the sparcs database included the patient's county of residence and his/her -digit zip code. to measure the combined effects of year, background characteristics (i.e., gender, age, race/ethnicity), and geographic location on the incidence of dog bites, we conducted a negative binomial regression analysis using the patient records from new york. a negative binomial regression analysis was performed instead of a poisson regression due to overdispersion of the data. the population-based counts of both the number of outpatients and inpatients who were bitten by a dog served as the dependent variable in this analysis. the predictor variables comprised the year, geographic location, and the demographic characteristics of the patients. year was measured as an interval-level variable ranging in values from (corresponding to the year ) to (corresponding to the year ). to capture possible curvilinear effects of year on the incidence of dog bites, a multiplicative term created by squaring the year variable was also incorporated into the analysis. geographic location was a dichotomous variable with a value of indicating new york city and a value of indicating new york state omitting new york city. gender was also a dichotomous variable with a value of indicating male and a value of indicating female. the age variable consisted of categories: under , to , to , to , to , to , and and older. the racial-ethnic background of patients was made up of groups as mentioned above: non-hispanic white, non-hispanic black, non-hispanic asian, non-hispanic other, and hispanic. since it can be assumed that the risk of being bitten by a dog varies by population sizes, an offset variable was introduced into the analysis. the offset variable was created in two steps. first, population counts were tallied for each combination of year, geographic location, gender, age group, and racial-ethnic category. so, for example, one count might comprise non-hispanic asian females between the ages of to living in new york city in . altogether, this step yielded different counts. next, natural log transformations were carried out on each of these counts. to measure the demographic correlates of the rate of dog bite injuries at the county level in new york state (n = ), a three-step process was undertaken. first, the number of both outpatients and inpatients were combined for each county for the year (the most recent year for which data are available). second, these figures were divided by the population of each county to obtain an injury rate. finally, the rates were correlated with an array of socio-demographic variables at the county derived from the american community survey - ( -year estimates) (u.s. census bureau ). these variables consisted of the following: ( ) population density per square mile, ( ) the racial-ethnic composition of the county, ( ) median family income, ( ) per capita income, ( ) percent of families with income below the poverty level, ( ) percent of the population and over with a b.a. degree or more, ( ) percent of the population with no health insurance, and ( ) percent of the insured population with public health insurance. a similar procedure was conducted to examine the socio-demographic correlates associated with dog bite injuries at the neighborhood level in new york city. for this analysis, the number of outpatients and inpatients were combined for each digit zip code in new york city (n = ). next these figures were aggregated up to the united health fund (uhf) level (n = ) and divided by the population of each uhf district to obtain an injury rate. these rates were then correlated with the same set of socio-demographic variables described above calculated for each uhf district. to determine the geographic distribution of patients injured by dog bites at the neighborhood level in new york city, a thematically shaded map of the injury rate by the united health fund (uhf) district in which the patient resided was created. a global moran's i was computed to assess whether the spatial distribution of the residences of the patients was geographically clustered or dispersed. the rates of dog bite-related injuries by age and sex for the period - are presented in table . consistent with previous research findings, the data show that age is strongly related to the rate of dog bite injuries (gilchrist et al. ; weiss et al. ; hoff et al. ; quirk ; holzer et al. ) . the modal category is the age group to , followed by the age groups to and to . from the age group to and older, injuries taper off considerably. the data also reveal that gender is associated with dog bite injuries. through the age of , the rate of males exceeds that of females by a wide margin. for the older age groups, the disparity between the gender groups narrows. table displays the annual estimated frequency and rates of dog bite injuries resulting in an ed visit in the united states from to . figure graphs the estimated annual rates. the data show that the rates of injuries tended to increase until and then underwent an overall decline thereafter (p = . for the curvilinear relationship). noteworthy is that the relationship between the incidence of dog bite injuries varies by age group over time. figure exhibits the rates of dog bite injuries resulting in a visit to an ed by age group during the time period to . paralleling the overall trend for the country as a whole, the rates of the two youngest age groups ( to , - ) initially increase up to and then undergo a steep decline. the opposite pattern prevails for the two older age groups ( - , plus). here the rates of these two groups increase over the course of the year span. the results of the negative binomial regression analysis examining the simultaneous effects of time and key demographic variables on the incidence of dog bites treated in an ed are displayed in table . the analysis is confined to two geographic locations -new york city and new york state excluding new york city. the predictor variables consist of year, year squared, place of residence, gender, age group, and the racial-ethnic background of patients. the effects of year and the multiplicative term of year squared are both significant. a graphic display of these terms indicates that from to the frequency of dog bite injuries increased and then from to decreased, controlling for the other variables in the analysis. the same general pattern emerges if the injury rate of just individuals who were admitted as inpatients serves as the dependent variable. both trends mirror the results observed at the national level. inspection of table indicates that residents of new york state outside of new york city are more likely to be treated in an ed for a dog bite than residents of the city. this finding reflects the greater prevalence of dog bite injuries in less densely populated areas. coinciding with the findings from the national data discussed above, the table also shows that there is a significant gender gap in the incidence of dog-related injuries. males are . times more likely to visit an ed due to a dog bite than females. as expected, age is a major determinant of the risk of injury from a dog bite. compared with patients who are and older (the reference category), patients aged to are . times more likely to incur a dog bite injury and patients aged to are . more likely to sustain an injury. individuals in the other age categories ( to , to , to , and to ) are also significantly more likely to be injured by a dog bite than those in the reference category. finally, the data reveal that non-hispanic asians are considerably less likely to be treated in an ed for a dog bite than hispanics (the reference category). the odds ratios for the other racial-ethnic groups are not statistically significant. table displays the relationship between key sociodemographic variables and the rate of injuries due to dog bites at both the county level in new york state and the neighborhood level in new york city. the data indicate that the rate of injuries due to dog bites is negatively associated with population density. this relationship between injury rate and population density is most pronounced at the county level. the data also show that at the county level, the injury rate is positively associated with the percent of the population which is non-hispanic white, reflecting the relationship between urbanicity and racial-ethnic composition. significantly, at both the county and uhf levels, there is a strong negative association between the injury rate and a number of economic variables. injuries are more prevalent in counties or neighborhoods with lower median family income, per capita income, or proportion of the population which is not college-educated. table presents the results of an analysis performed on self-reported incidents of dog bites in new york city's united health fund districts for the years to . the table shows the socio-demographic correlates of both the percent of dogs which were spayed/neutered and the percent of dogs which were pit bulls in the uhf districts. of the breeds identified in the data set ( . %), pit bulls were the most numerous ( . %), followed in order by shih tzu ( . %), chihuahua ( . %), german shepherd ( . %), and yorkshire terrier ( . %). this finding is consistent with previous research showing that pit bulls are responsible for more bites than any other dog breed (mcreynolds ). of the selfreported cases . % were classified as spayed or neutered. the results reveal that poorer neighborhoods were associated with a higher proportion of dogs which had not been spayed/neutered and also a higher proportion of dogs which were pit bulls. coinciding with expectations, the rates of dog-bite injuries are not uniformly distributed across the uhf districts. a choropleth map of the rates shows that the hunts point-mott haven neighborhood in the bronx, east harlem neighborhood in manhattan, the sunset park neighborhood in brooklyn, and the port richard and stapleton-st. george neighborhoods in staten island have notably higher rates than other uhf districts (see fig. ). the moran's i index yields a value of . (p < . ), indicating a pattern of spatial clustering . surveys of dog owners during the last decade reveal significant changes in their demographic characteristics (table ). the data in the table shows that the age distribution of dog owners has skewed upwards in the past decade. in , . % of dog owners fell into the age category of to ; by , the number of owners in this age category rose to . %. in this same -year span of time, dog owners were also more likely to be hispanic, reside in larger metropolitan areas, and have higher levels of education. another noteworthy change is the reduction in the number of younger children living in the household. the number of children in each of the age brackets under , to , and to all dropped in the years from to . this study has found that the rate of dog bite injuries has been declining in recent years. this decline is in evidence at both the national and state levels of analysis. the decline has been most visible among those under the age of particularly children under the age of . one explanation for this downward trend might be that it is simply an artifact of the methodology employed in this study. most of the findings contained in this study are based on dog bite injuries treated in emergency room departments. it may be the case, though, that in recent years individuals bitten by dogs have increasingly sought treatment in other venues such as private physicians' offices or urgent care centers. while this may be a factor associated with the downward trend in dog bite injuries, another finding uncovered in this study --a decline in the number of inpatients treated for dog bites in new york --does not lend support to this explanation. a second explanation for the recent decline in dog bite injuries centers on the change in the profile of dog owners and the characteristics of the dogs themselves. survey data presented in this study indicates that there has been a decline in the presence of young children in dog-owning households over the past decade. since young children are the most likely age group to be bitten by dogs and the overwhelming majority of injuries in the united states occur in the home, the reduction in the number of younger-aged children living at home would help to explain the drop off in dog-related injuries (gilchrist et al. ; weiss et al. ; quirk ; overall and love ) . the survey data further shows that dog owners are increasingly residing in larger metropolitan areas where dog sizes tend to be smaller. also, the dogs are more likely to be confined indoors or in a yard, and kept on a leash (marketresearch.com ). as research has demonstrated, small and medium size dogs pose less of a danger to humans and dogs on a leash lower the risk of unwanted contacts with humans. the survey data also reveals that over the past decade owners have become older and better educated. this shift in age and education is consistent with the notion that the role of the dog has changed from being less of a guard dog and more of a pet or family member. a nationwide harris poll of adult americans buttresses this notion. the poll found that among dog owners, % view their dogs as members of their family (harris poll ). significant numbers report that they "allowed my pet to sleep in the bed with me" ( %), "bought my pet a holiday present" ( %), thought "it was a good idea to have dogs in long-term care facilities" to reduce stress ( %). the surge in the number of dog parksdesigned to better meet the physical and emotional needs of dogs --is another indicator of the changing role of the dog in american life. in the last decade there has been a % increase in dog parks, according to the trust for public land (lowrey ) . thus, it is likely that the changing role of the dog in u.s. also accounts for the lower incidence of dog bite injuries. while there has been a diminution in the rate of injuries due to dog bites in recent years, dog bites still remain a leading cause of nonfatal injuries in the united states. for the year the most recent year for which nationwide data are available --there were a total of , nonfatal injuries treated in an ed due to dog bites. as this study has noted, there is a distinctive sociodemographic profile of individuals who suffer an injury from a dog bite. sizable age disparities exist, with younger individuals considerably more likely to be treated for a dog bite than older individuals, especially school-age children. numerous reasons have been given to account for the greater susceptibility to dog bites on the part of young children. children may lack the maturity to understand the "signaling behavior" of dogs, misinterpreting the cues dogs emit when in an agitated state. children may also make sudden body movements or high-pitched sounds which can frighten dogs and precipitate an aggressive response (overall and love ) . in addition, because of their "innate curiosity," children may more readily approach strange dogs (cohen-manheim et al. ) . aside from age, significant associations also exist between dog bite injuries and the place of residence and the economic background of patients. dog bite injures are more prevalent among inhabitants of less densely populated areas and poorer neighborhoods. the negative relationship between the incidence of dog bites and the socioeconomic status of the neighborhood could be due to several factors. first, dogs might lack proper training or be taught to act aggressively to protect the household. second, they may lack the necessary supervision by being chained outdoors for lengthy periods of time or being allowed to run loose. third, as the data in this study has demonstrated, the owners may not be compliant with the licensing requirements such as spaying or neutering their dogs. though dog bites remain a sizable problem, it is one which is largely preventable. in this study we have found that dog bite injuries tend to be clustered in identifiable neighborhoods. dog bite prevention programs as well as stricter enforcement of dog laws can target these neighborhoods to significantly reduce the incidence of injuries. some limitations attached to this study should be noted. one is that population counts of dogs and specific breeds within new york city neighborhoods are not available. thus, we cannot determine the degree to which the varying prevalence of dog bite injuries in new york city's neighborhoods is due to the differing number of dogs in these neighborhoods. nor can we determine whether pit bulls rank as the most dangerous breed in new york city because of their attributes, or because of their numerical representation in the city. a further limitation pertains to the self-reported data on dog bites in the city. dohmh states on their web page that "data on breed, age, gender and spayed or neutered status have not been verified by dohmh and is listed only as reported to dohmh". a third limitation pertains to the underlying reasons for the variability in the annual rate of dog bite injuries in the united states, particularly in the last several years. while we believe that this variability reflects a real diminution in the rate of dog bite injuries, we cannot dismiss the possibility that some of this variability might be due to data quality issues. this study has found that the rate of dog bite injuries in the united states has decreased in recent years. we attribute this decline mainly to a shift upwards in the age distribution of dog owners and to the changing role of the dog in american families from being less of a guard dog to being more of a companion. as dog ownership continues to spiral upwards (a trend which has been accelerated by the coronavirus and subsequent lockdowns), it will be important to monitor the frequency of dog-bite related injuries to see if this positive trend persists. though dog bite injuries have declined in recent years, the extent of these injuries still constitutes a major health problem. young children especially are vulnerable to being bitten by a dog. prevention programsparticularly those which center on teaching the dangers of canine interactions with humansshould be targeted at this age group. this study also has noted that residents of poorer neighborhoods in urban areas are more susceptible to being injured than residents of more affluent neighborhoods. future research needs to be conducted to increase our understanding of why there is a negative association between a neighborhood's socioeconomic status and injury rates from dog bites. hopefully this greater understanding will lead to a reduction in the disparity of these rates. american society of plastic surgeons. national plastic surgery statistics number of dogs in the united states from unreported dog bites in children national center for injury prevention and control. web-based injury statistics query and reporting system (wiaqars) epidemiology of hospitalizations due to dog bite injuries in israel dog bites: still a problem? injury prevention americans-have-always-had-interesting-relationships-with-their-pets-whetherthat-pet-is-a-cat-dog-parakeet-or-something-else-the-pet-industry-is-thrivingand-for-good-reason-more-than-three-in-f emergency department visits and hospitalizations resulting from dog bites dog bite injuries in the usa: prevalence, correlates and recent trends statistics#:~:text=pet% insurance,-the% pet% insurance&text=the% total% number% of% pets,insurance% companies% in% north% america the demographics of dog bites in the united states new york times. . section b, . marketresearch.com. topline pet demographics. in: private correspondence new study identifies most damaging dog bites by breed: newstat dog bites to humans-demography, epidemiology, injury, and risk ownership of small dogs is on the rise non-fatal dog bite injuries in the usa american community survey product safety commission. injuries associated with selected sports and recreational equipment treated in hospital emergency departments, calendar year incidence of dog bite injuries treated in emergency departments publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors would like to thank marketresearch.com for furnishing us with information on the changing demographics of dog owners in the united states, and for their helpful comments concerning the interpretation of the data. the authors would also like to thank yonatan gorin, master's student in business administration at touro university worldwide, for the technical assistance he lent to this study. we also would also like to acknowledge the many helpful comments provided by the anonymous reviewers. pst conceptualized and designed the study; collected and analyzed the data; and wrote the initial draft of the manuscript. wm collected and analyzed the data and revised the manuscript. both authors approved the manuscript for publication. funds to acquire some of the data used in this study were obtained through hunter college's president's fund of faculty advancement. the wisqars database can be accessed online (https://www.cdc.gov/injury/ wisqars/nonfatal.html). information about obtaining the sparcs data can be obtained by contacting the new york state department of health (https:// www.health.ny.gov/statistics/sparcs/). the dohmh data can be retrieved online https://data.cityofnewyork.us/health/dohmh-dog-bite-data/rsghakpg. this study uses publicly available aggregate data at the national, county, and local levels and employs de-identified individual-level data for state and local-level analyses. we are therefore exempt from securing human subjects review from our college's institutional review board. not applicable. the authors have no conflict of interest to declare. key: cord- -apb l tq authors: ward, m.p.; kelman, m. title: companion animal disease surveillance: a new solution to an old problem? date: - - journal: spat spatiotemporal epidemiol doi: . /j.sste. . . sha: doc_id: cord_uid: apb l tq infectious disease surveillance in companion animals has a long history. however, it has mostly taken the form of ad hoc surveys, or has focused on adverse reactions to pharmaceuticals. in a blue ribbon panel was convened by the u.s. white house office of science and technology policy to discuss the potential utility of a national companion animal health surveillance system. such a system could provide fundamental information about disease occurrence, transmission and risk factors; and could facilitate industry-supported pharmaco-epidemiological studies and post-market surveillance. disease watchdog, a prospective national disease surveillance project, was officially launched in january to capture data on diseases in dogs and cats throughout australia. participation is encouraged by providing registrants real-time disease maps and material for improved communication between veterinarians and clients. from january to mid-november , an estimated % of veterinary clinics australia-wide joined the project. over disease cases – including canine parvovirus (cpv), canine distemper, canine hepatitis, feline calicivirus, feline herpesvirus, and tick paralysis – were reported. in new south wales alone, cpv cases in dogs were reported from postcode locations. new south wales data was scanned using the space–time permutation test. up to clusters (p < . ) were identified, occurring in all months except march. the greatest number of clusters (n = ) were identified in april. the most likely cluster was identified in western sydney, where cases of cpv were reported from a postcode in february. although the project is still in its infancy, already new information on disease distribution has been produced. disease information generated could facilitate targeted control and prevention programs. surveillance of infectious diseases in companion animals has a long history. this surveillance has mostly taken the form of ad hoc surveys, or has focused on adverse reactions to vaccines and other pharmaceuticals. most of these activities have not included an ongoing measurement of the population using comparable methods, so strictly do not meet our current understanding of disease surveillance. a notably exception is surveillance for rabies, for which passive surveillance systems exist (for example, see blanton et al., ; tenzin et al., tenzin et al., , . an example of using secondary data sources for surveillance is research on the recent epidemic of canine leptospirosis in north america (for details, see ward et al., ward et al., , a ward, a,b) . this research program was initiated using data from the veterinary medical database (vmdb). the vmdb was established in north america in by the national cancer institute to collect, store, and retrieve veterinary clinical information (hayes et al., ; priester, ) . it contains a standardized abstract of every animal examined at participating veterinary teaching hospitals in the united states and canada. at the time of initiation of this study, veterinary teaching hospitals in the united states and canada had contributed data (ward et al., ) . results showed a clear trend in increasing diagnoses of canine leptospirosis, suggesting this to be a re-emerging zoonosis. however, because the vmdb is a secondary data source, data analysis was limited to those covariates recorded in the vmdb, and results might be subject to diagnostic bias and might not necessarily represent the target population. for spatial analyses (ward, a) , research was limited to the location of the hospitals reporting the cases. later, data generated within a specific veterinary teaching hospital data management system was integrated (using a geographic information system) with data generated from a state veterinary laboratory accession management system to conduct more focused research on spatial distribution and risk factors (ward et al., a,b) . this allowed recommendations to be made to reduce the impact of this epidemic of leptospirosis. however, integrating databases and data cleaning, error checking and validation consumed a considerable amount of time, and the system could not identify new trends in near-real time. a critical gap identified was database integration and analytical methodologies that could be applied routinely. most research in the area of companion animal disease surveillance has focused on systems to detect adverse vaccine and other drug reactions. for example, moore et al. ( a) developed a surveillance system that utilized electronic medical records from a large corporate small animal general practice in the united states, in which each of more than hospital locations in this system used the same computerized medical record system. records of dogs receiving a range of vaccines (including for bordetella, coronavirus, multivalent distemper-adenovirus-parainfluenza-parvovirus-leptospirosis, giardia and rabies) were extracted and searched for adverse reactions. using the collective data recording of these hospitals, adverse events were identified during a -year period, representing , , doses of vaccine administered to , , dogs. the use of veterinary practice databases to complement spontaneous reporting systems for vaccine safety is one example of recent advances in companion animal disease surveillance (moore et al., b) . this system has also been used as a research tool to identify space-time clusters of adverse events associated with canine rabies vaccine (moore et al., ) . in september , a blue ribbon panel was convened on behalf of the u.s. white house office of science and technology policy to discuss the potential utility and possible strategies for design and implementation of a national companion animal health surveillance system (stone and hautala, ) . a goal of such a system is improved veterinary care, and it could be also used to develop evidence-based veterinary practices. data derived from a surveillance system could provide fundamental information regarding disease incidence, prevalence, transmission, and risk factors. such an enhanced understanding of disease epidemiology would enable practitioners to evaluate the effectiveness of treatments and intervention programmes. such a system could also facilitate industry-supported pharmaco-epidemiological studies and post-market surveillance, which would enable the development of safer and more effective veterinary products. as stated by the blue ribbon panel, a companion animal surveillance system should ideally be a public/private partnership involving representatives from the veterinary community and the veterinary products industry who are involved in the design of the system in order to promote compliance and leverage resources. in january , virbac animal health in australia launched disease watch-dog, a prospective national disease surveillance project, to capture data on communicable disease cases and outbreaks, with the ultimate aim of the reduction and control infectious diseases in cats and dogs. this project is unique as it involves a growing number of participants, and as well as gathering data, encourages participation by providing benefits to registrants including real-time maps of disease occurrences and outbreaks, material for improved communication between veterinarians and clients, and empowerment of staff. from january to mid-november, an estimated % of veterinary clinics australia-wide have joined the project, with > cases of disease reported. while the project is still in its infancy, the analysis of initial data is demonstrating some important findings with respect to disease distributions in space and time and risk factors, and there is considerable potential to gather vital information that could lead to targeted vaccination and treatment efforts which could be the key to the control of various diseases. in this paper we report details of this surveillance tool and illustrate its utility with a case study of canine parvovirus (cpv) occurrence and distribution during a -month period in the state of new south wales. the purpose of this paper is to demonstrate the feasibility of surveillance in pet animal populations, and to highlight the value of spatial analysis of such surveillance data. disease watchdog was created out of the need for better epidemiological data on current and emerging companion animal diseases. despite significant advances in technology, veterinary science is lacking recent studies on the occurrence and distribution of diseases that affect the lives of millions of animals worldwide. incidence of common infectious diseases such as canine parvovirus (cpv), canine distemper virus (cdv), feline calicivirus (fcv), feline rhinotracheitis virus (fvr), feline immunodeficiency virus (fiv), and feline leukemia virus (felv) are largely unknown. with comprehensive data and a better understanding of the epidemiology of these diseases, solutions to problems such as how to formulate best practice vaccination protocols during disease outbreaks or how to strategically address endemic disease with preventive and treatment techniques can be proposed. as a national disease surveillance system, disease watchdog was developed to gather epidemiological data and to provide real-time mapping that demonstrates disease occurrences at suburb level. data needs were based on the following considerations: fields in which data could be recorded were then assembled into a web-based system and the website interface carefully designed to maximize compliance from users. estimated time to enter a case of disease is currently s. features to improve compliance include a ''litter'' checkbox where multiple affected littermates can be simultaneously entered into the database, reducing repetitive data entry. a chart can be downloaded from the website so that users can record cases on paper as an interim measure, then enter cases in a batch if this is easier for the user. to maximize accuracy, user access to submit data is limited to registered veterinarians and veterinary nursing staff of veterinary clinics. veterinary clinics register for access to the disease watchdog site at www.diseasewatchdog.org and once approval is granted, an email provides username and password. there is no charge for using disease watchdog. once a month, all registered users are sent an email reminder to enter cases for the previous month if they have not already done so. the monthly email also provides an opportunity to communicate with users, updating them on improvements to the system and how best to use the program. when a user registers, a pack of resources is sent to the clinic to which they belong, to help communicate their involvement to their staff and clients. an emphasis on empowerment of staff to be involved in the program aims at encouraging participation and collegiality. the message behind the program is that together, the veterinary profession has the power to control diseases through participation in the program, data collection, analysis and then strategic disease prevention and treatment. a benefit for veterinary clinics of participating in disease watchdog is the ability to view maps of disease cases and outbreaks in real-time. data entered via the website is immediately visible on the disease maps that any registered participant can view. maps can then be used to show clients where at-risk areas for disease exist, highlight the importance of disease prevention, and to monitor disease outbreaks in their local area. measurement of disease cases and recording of outbreaks also provides strong data that can also be communicated through channels such as the australian veterinary association's media office, to allow alerts to be transmitted to the general public via local and national media. never before in australia has accurate recording of disease outbreaks been available on this scale for this number of diseases. a feature of disease watchdog is the role of disease surveillance champions. these are individuals within veterinary practices that are responsible for data entry. these individuals routinely update data within the system, for their practice, on a monthly basis. they act as the primary contact point within each practice, and promote the advantages of the disease watchdog surveillance system to colleagues and clients. disease watchdog was upgraded to version . in september , partly in response to suggestions and ideas for improvements from contributors. this upgrade provided both contributors and analysts with a number of additional features and benefits for better searching and display of disease cases and outbreaks, and improved recording of information. some of the important news features include: . allowing the graphing feature to be controlled by disease surveillance champions. this feature displays disease cases and outbreaks -enabling the diseases, locations and timeframes that are displayed to be personally selected, for better representation of disease outbreaks relevant to a local community. disease watchdog users can adjust the graph that displays on the home page, to suit the needs of their individual clinic. the graph of current outbreaks of disease defaults to the last months. . a new facility to search by radius around a suburb, providing more relevant information on the diseases in the user's area and allowing improved mapping. this facility could also be useful for research studies to identify risk factors for disease occurrence. . a feature to allow multiple diseases to be displayed by assigning different colors to each disease, so that multiple diseases can be shown simultaneously. more information on diseases in a suburb can be obtained by the user simply by clicking on a colored flag placed at the suburb location. displaying multiple diseases allows practices and their clients to visualize which diseases are prevalent in their specific area. . tick paralysis data has been added to disease watch-dog. tick paralysis is an acute, progressive ascending motor paralysis. it is caused by a salivary neurotoxin produced by some species of ticks. in australia ixodes holocyclus is the principle cause of cases of tick paralysis in domestic animals. this tick species can be found on native animals along the east coast of australia. reported distribution of tick paralysis has previously been mostly anecdotal. inclusion of tick paralysis in disease watchdog allows for the first time the spatial and temporal distribution of this important disease to be monitored in australia. recording tick paralysis cases will enable veterinarians to alert clients to the dangers of ticks in specific areas, and also whether tick paralysis is seasonal in their area and the importance of tick prevention and awareness. . two more infectious diseases were added to the disease watchdog list; the distribution of felv and feline infectious peritonitis (fip) can now be monitored. these diseases were chosen as the next additions because of their apparent lower prevalence, but higher mortality. felv is caused by a retrovirus that can be transmitted between cats via saliva or nasal secretions, and can be fatal. fip, caused by a coronavirus, is incurable and generally fatal. other diseases will be added to disease watchdog in the future, based on the perceived health importance and ability of veterinarians to detect and diagnose the health condition. the development and maintenance of disease watch-dog to date has been funded entirely by virbac animal health. awareness of the disease watchdog initiative is being achieved within the veterinary community via the support of the australian veterinary association (which represents most veterinarians within australia), idexx laboratories (a company that develops and markets diagnostics within australia; http://www.idexx.com.au/), vetnostics (part of a network of pathology laboratories operating throughout australia; http://www.vetnostics.com.au/), and gribbles veterinary (a veterinary pathology organization providing veterinary diagnostic and analytical services throughout australia and new zealand; http://www.gribblesvets.com.au/info/general/home/get/ / /). between january and november , registrants joined disease watchdog across australia (a small number are non-veterinary registrants and do not record disease cases), representing approximately % of veterinary clinics australia-wide. based on estimates of veterinary clinic numbers across the states of australia, participation levels range from % in victoria ( ) to % in new south wales ( ). to demonstrate the utility of the disease watchdog system, data analysis focused on reports of cpv in the state of new south wales. cpv is an infectious disease of dogs caused by cpv type . it is highly contagious and is spread via direct contact or indirectly via fecal contaminated environments and fomites. this disease is often diagnosed in puppies unprotected by maternal antibodies or vaccination. although cpv first appeared in the late s as a pandemic (johnson and spradbrow, ; walker et al., ) and other epidemics have been reported (sabine et al., ) , the spatial distribution, seasonality and risk factors for cpv are not well understood. in a questionnaire survey of veterinary practitioners in australia and new zealand seeking details of their experience with cpv infections in , sabine et al. ( ) found that explosive outbreaks of disease had occurred in most parts of australia in that year. no obvious pattern of spread over the continent could be detected. an overall mortality rate of % was estimated. in a serological survey, smith et al. ( ) found that cpv was generally a disease of dogs less than months of age. the current analysis focuses on the spatial distribution of this disease, as a case study of the application of the disease watchdog surveillance system. data extracted from disease watchdog included date of diagnosis and the residential postcode. for the purposes of demonstration, data selected was restricted to reported cases occurring between january and september, in the state of new south wales. all data was joined to a postcode shapefile (gda , new south wales lambert conformal conic projection) in arcgis v. . (esri inc., redlands ca). the lambert conformal conic projection system is one of the best for 'middle' latitudes. the state of new south wales lies between latitudes and °s. spatial relationships were measured on the scale of meters. only cases which had valid data entered for location (postcode) and diagnosis date (day, month) were included in spatial analyses. for all postcodes included in the study, the postcode centroid was calculated (arctools, arcgis . ). most postcode polygons in new south wales are relatively small: % of the postcodes cover a land area of km . data were scanned using the space-time permutation test (satscan v. . kulldorff m. and information management services, inc. satscantm v . : software for the spatial and space-time scan statistics. http://www.satscan.org/, ). the permutation test was used because the number of dogs at-risk of cpv per postcode is unknown. however, it was assumed that during the -month study period the distribution of the population of dogs would have remained stable across postcodes. future research using disease watchdog will include estimation of the dog and cat population at-risk within suburbs and postcodes. this might be achieved by annual surveys of disease watchdog participants, or by estimations based on reported disease cases. based on a maximum period of infectiousness for cpv of up to - weeks (goddard and leisewitz, ) , the temporal scanning window was restricted to days, with windows of , , and days used. the spatial scanning window was restricted to km, with windows of , , and km used in a series of separate analyses. the analytical approach, recognizing that it was a demonstration of the application of the disease watchdog surveillance system, was exploratory and attempted to provide insights into the epidemiology of cpv in the new south wales dog population -a subject on which no peer-reviewed information has previously been published. the selection of scanning windows was motivated by an assumed level of clustering that might occur within an area covered by up to - postcodes (in urban and semi-urban areas of new south wales) within a relatively short timeframe, i.e., potential local outbreaks of cpv. an additional exploratory analysis was performed using the scan statistic bernoulli model. for these analyses, cases were reports of cpv in which the affected dogs had been vaccinated and controls were those dogs diagnosed with cpv that reportedly had not been vaccinated. the results of such an analysis might reveal clusters of cpv disease associated with vaccine failure. in all scan statistic analyses, permutations were performed and significant (p < . ) clusters were identified and mapped. clusters were interpreted based on the ratio of observed to expected cases occurring within the cluster. data was exported from disease watchdog, processed within arcgis v. . (esri inc., redlands ca) and then exported to satscan v. (kulldorff m. and information management services, inc. satscan™ v . : software for the spatial and space-time scan statistics. http:// www.satscan.org/, ) for analysis. between january and september, , there were reports submitted to disease watchdog, representing disease cases. only one case of fip, and two cases each of cdv and chv, were reported. a total of and cases of fcv and fhv were reported, respectively. tick paralysis was added to disease watchdog in september, and cases were reported during this month. all reports contained valid data for diagnosis and postcode. during the study period, cases of cpv were reported from new south wales ( cases/ reports), queensland ( / ). victoria ( / ), western australia ( / ), the northern territory ( / ), south australia ( / ) and tasmania ( / ). in new south wales, most cpv reports ( ; %) consisted of only one case. reports with , , , , and cases were made on , , , , and occasions. most of the cases were male ( ; %). a total of breeds were reported to be affected. the following breeds accounted for > % of cases: australian cattle dog ( ; %), staffordshire terrier ( ; %), jack russell terrier ( ; %), bull terrier ( ; %), mastiff ( ; %), maltese ( ; %) and fox terrier ( ; %). the mean ( % confidence interval) and median (interquartile range) ages were ( - ) and ( - ) months, respectively. the minimum age of cases was months. the most common methods of diagnosing cpv were the elisa snap ( ; %) and clinical signs ( ; %). immunofluorescence and pcr were rarely used ( and , respectively). outcome was reported for cases, with treatment ongoing at the time of reporting for a further cases. of those cases with a final outcome reported, ( %) died, ( %) were euthanized, and ( %) recovered. vaccination status was reported for cases, of which ( %) cases were vaccinated. no significant association was found between survival status (recovered versus died or euthanized) and gender (male versus female, odds ratio (or) . ; p = . ), method of diagnosis (clinical versus test, or . ; p = . ) or vaccination status (unvaccinated versus vaccinated, or . ; p = . and unknown versus vaccinated, or . ; p = . ). dogs that survived were older ( weeks) than those that died ( weeks), p = . . the greatest number of cases of cpv were reported in the months of february and april ( % each). half of all cases were reported between march and june. the data entry screen in disease watchdog (www.diseasewatchdog.org) is shown in fig. . examples of the reports that can be generated and viewed on the disease watchdog website are shown in fig. . reports include histograms showing the frequencies of diseases reported during a given period, and maps of the distribution of cases. an example of the spatial search capacity of disease watchdog is shown in fig. . cpv cases were reported from postcodes. only one case was reported from postcodes; or more cases were reported from the following postcodes: , , , , , , , , (fig. ) . only of these ( and ) were in areas of substantial human population. regardless of the size of the scanning window used (all combinations of , , and km and , , and days), the most likely cluster was identified in western sydney, in which clinics reported cases of cpv on february (observed Ä expected . ). depending on the scanning window used, between and significant (p < . ) additional clusters were detected. at larger spatial scanning windows, fewer clusters were detected. the size of the temporal scanning window had little influence on the number of clusters detected. clusters were detected in every month except march. the most clusters were identified in april. twelve of these clusters were only of one day duration; the other clusters lasted from to days (median days). the clusters (fig. ) were distributed throughout most of the state, excluding the southeast and the far west. all but two of these clusters were located outside the metropolitan area of sydney. using reports of cpv in which the affected dogs had been vaccinated as cases and controls as those dogs diagnosed with cpv that reportedly had not been vaccinated, the same location in western sydney was identified as the primary cluster, although the observed Ä expected ratio was less ( . ). in contrast, in this analysis no significant (p < . ) secondary clusters were detected. surveillance of small animal populations for infectious diseases has been rare. almost all examples of surveillance systems focus on the detection of rabies cases. for example, in the united states the system for rabies surveillance is well-developed and based on the reporting of cases (usually accompanied by submission of diagnostic samples) to the centres for disease control and prevention. however, even in this system, the focus is cases in wildlife, rather than companion animals (for example, in approximately % of the cases were in wildlife, and % were in domestic animals; blanton et al., ) . other studies have used a surveillance-like design. for example, biggeri et al. ( ) used a -stage sampling design, with first stage transects, to study the risk of dog parasitic infections in the city of naples, italy, during - . this system focused on zoonotic parasitic diseases, including infections with trichuris, isospora, toxascaris, ancylostoma and toxocara. however, the study apparently was driven by a research goal and not as an ongoing effort, thus, not strictly matching the definition of surveillance. other initiatives have used existing hospital management systems as a secondary data source for monitoring diseases in companion animal populations. for example, moore et al. ( ) used databases complied by banfield, the pet hospital corporation in the united states to describe several diseases. development of a disease surveillance system for companion animal disease as a primary objective apparently has not been successfully undertaken previously. the blue ribbon panel convened on behalf of the u.s. white house office of science and technology policy in to discuss the potential utility and possible strategies for design and implementation of a national companion animal health surveillance system (stone and hautala, ) stressed the importance of consultation with end-users: ''the type of information collected, the frequency with which it is collected, and the format in which it is disseminated should be determined in accordance with user goals''. disease watchdog is unique in its flexibility and ability to be modified in response to suggestions by those who use the system. for example, the upgrade of the system in september included several features identified as important by end-users, such as graphing and displays capabilities, and the addition of new diseases such as tick paralysis. the blue ribbon panel also identified four fundamental principles relevant to the design of a companion animal surveillance system: syndromic versus disease-specific surveillance; the ability to leverage existing systems; predefined response protocols; and integration with other health surveillance systems. syndromic surveillance involves collection of information on clinical syndromestwo or more characteristic clinical signs. disease watchdog is based on the diagnosis and reporting of specific disease, rather than syndromes. expansion of disease watchdog to include syndromes (for example, vomiting and diarrhea) could be implemented with comparative ease. however, such a modification would need to be driven by the endusers, which are primarily veterinary practices. in the case of cpv, a substantial proportion ( %) of cases was diagnosed using the snap elisa. in this situation, reporting cases based on syndrome might not provide additional benefit to the end-user. in contrast, cases of tick paralysis are generally diagnosed based on clinical signs (for exam-ple, between and september the reported cases of tick paralysis were diagnosed based on clinical presentation ( %), tick found ( %) or tick crater only found ( %)). tick paralysis was added to disease watchdog in september in response to requests from end-users of the system. for an applied surveillance system such as disease watchdog, the usefulness of syndromic surveillance needs to be assessed in partnership with the enduser. acute cpv enteritis can reportedly occur in dogs of any breed, age, or sex. however, puppies between weeks and months of age appear to be more susceptible (goddard and leisewitz, ). in the current study the median (interquartile range) age of reported cases was ( - ) months. this finding was unexpected, based on previous statements regarding the age pre-disposition for cpv. of those cases with reported vaccination status, only % of cases were vaccinated. this might, in part, explain a higher age of cases than expected. however, the common belief amongst veterinarians that cpv is a disease of puppies may need revision, following further research using data generated by disease watchdog. some breeds -mostly large breeds such as rottweiler, doberman pinscher, labrador retriever and german shepherd dog -have been reported to be more at risk for severe cpv enteritis (goddard and leisewitz, ) . none of these breeds were commonly reported to be cases in the current study. however, the proportion of a breed in a population -and the proportion that are presented at veterinary clinics -needs to be taken into account before breed predisposition can be determined. goddard and leisewitz ( ) state that the risk of cpv in sexually intact males is twice that of sexually intact females. in the current study more reported cases were male than female, but the difference was small ( % versus %). half of all cases were reported between march and june, which represents the autumn months. generally cpv is considered to peak in summer (goddard and leisewitz, ) . as more data is accumulated in disease watchdog, a more accurate description of seasonality can be made. many clusters of cpv were identified during the short -month study period in new south wales. such a spatial distribution of cases is likely to indicate that local factors are important, generating local epidemics. follow-up studies, using larger datasets, might be able to identify some of these factors. based on preliminary analysis, apparently vaccination practice is unlikely to explain most of these clusters. there are three specific design elements for a companion animal surveillance system (stone and hautala, ) : target population; data collection, analysis and standards; and mechanisms for dissemination of results. the system must have a clearly defined target population. this is necessary so that the disease frequency estimated can be referred to a defined population. in disease watchdog, the target population is comprised of veterinary practices that report disease cases. this is a subset (currently nearly onethird) of all practices in australia, the reference population. 'all practices in australia' is a well-defined population, since practices need to be licensed by the relevant state or territory authority where they operate. a current gap in disease watchdog is that the population of dogs and cats (and their demographics -such as age, breed and gender distributions) -is unknown. such data -when available -is for specific locations only (toribio et al., ) . this information could potentially be collected within the disease watchdog system, for example by having contributors annually describe their practice caseload during the previous months, or by estimating the likely population at-risk based on the proportions of cases reported, and potentially informed by known covariates (for example human population size and socioeconomic status) within the practice area. variable disease watch-dog adoption proportions for different australian statescurrently ranging from % in victoria to % in new south wales -means that inferring the impact of disease in different areas needs to be done with caution. a companion animal disease surveillance system should collect a comprehensive data set comprising both clinical and epidemiological data (stone and hautala, ) . disease watchdog collects spatial information via the postcode of the owner's address. it is assumed that this is the area in which the animal has spent most time during the short period preceding disease diagnosis, and assumed to be the area that other animals are at risk of the same disease. the actual date of diagnosis is reported in disease watchdog. diseases currently reported in this system can be diagnosed on the basis of clinical presentation, diagnostic test (including elisa snap, immunofluorescence, pcr) or other. other information collected includes animal name, suburb, state, postcode, species and breed, age (years/months/weeks), sex, neuter status, whether a litter was affected and if so, the number of animals in the litter and the total number affected, case outcome (recovered, died, euthanized, treatment ongoing) and vaccination status and date. a unique case identification number is generated by the system, and the case is linked to the clinic name and the veterinarian's name. finally, within a surveillance system, each user should define triggers for implementing responses and identify data that will support specific responses (stone and hautala, ) . within disease watchdog, the response to perceived clusters of disease rests with the end-user, the veterinary clinic. a feature of this system is the ability for practices to conduct spatial searches within their local area. this allows veterinarians and veterinary assistants to promote disease control and prevention based on empirical data. this might be one reason why the adoption of disease watchdog has been high during its first months of operation. two tasks that could facilitate major advances in the surveillance of companion animal populations are standardization of data captured within such systems, and the development of a set of core analytical tools. a current barrier to disease surveillance is an inability to rapidly and validly integrate different surveillance systems. the barrier is usually a lack of consistency in the scale (spatial, temporal) at which data is recorded, a lack of standard case definitions (e.g. method of diagnosis, method of measurement) and differences in which auxiliary data is recorded (e.g. animal data such as age, gender, breed and population demographic data -the 'population at-risk'). identifying key surveillance systems and key individuals, an agreement on standards that should be used could be reached. an analogy is the recent development of the reflect statement: methods and processes of creating reporting fig. . the distribution of spatio-temporal clusters of cases of canine parvovirus reported in the disease watchdog surveillance system between january and september in new south wales, australia. clusters were detected using the scan statistic permutation test, with spatial scanning windows up to km radius and temporal scanning windows up to days in length. guidelines for randomized control trials for livestock and food safety (o'connor et al., ) . an array of analytical tools are available for detecting trends and clusters in disease surveillance data (for example, see ward and carpenter, a,b; ward, ) . there is a lack of consistency regarding which tools should be applied routinely, and also a lack of knowledge of the performance of the different tools applied to different types of surveillance data. as above, agreement is needed in order to correctly evaluate the results of analysis of surveillance data. to our knowledge, results of the analysis of the spatial distribution of cpv cases have not been published in the peer-reviewed literature. a likely barrier is the lack of large, good quality surveillance datasets. disease watch-dog fills that gap: in new south wales alone, cases were reported during just months. considering the lack of knowledge of spatial distribution of cpv and the lack of knowledge of the population at-risk within each postcode, we used the permutation model. the model does not require any assumptions to be made with respect to how the population at-risk is characterized. the only assumption is that the population at-risk remains relatively stabile during the study period. as more analyses are undertaken of the spatial distribution of diseases in pet populations, analytical approaches are likely to be refined. during a short period of operation, disease watchdog has been adopted by nearly one-third of australian veterinary clinics. epidemiologic data, including location and date, are providing new insights into the distribution of diseases of dogs and cats in australia. ability of end users to produce disease maps is one likely explanation of its success to date. disease mapping in veterinary epidemiology: a bayesian geostatistical approach rabies surveillance in the united states during canine parvovirus the veterinary medical data program (vmdp): past, present, and future isolation from dogs with severe enteritis of a parvovirus related to feline panleucopaenia virus a space-time cluster of adverse events associated with canine rabies vaccine postmarketing surveillance for dog and cat vaccines: new resources in changing times adverse events diagnosed within three days of vaccine administration in pet dogs the reflect statement: methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety multiple primary tumours in domestic animals. a preliminary view with particular emphasis on tumors in dogs canine parvovirus infection in australia during canine parvovirus-five years later serological observations on the epidemiology of parvovirus enteritis of dogs meeting report: panel on the potential utility and strategies for design and implementation of a national companion animal infectious disease surveillance system reemergence of rabies in chhukha district re-emerging rabies in dogs and other domestic animals in eastern bhutan demographics and husbandry of pet cats living in sydney, australia: results of cross-sectional survey of pet ownership a serological survey of canine parvovirus infection in new south wales clustering of leptospirosis among dogs in the united states and canada seasonality of canine leptospirosis in the united states and canada and its association with rainfall spatio-temporal analysis of infectious disease outbreaks in veterinary medicine: clusters, hotspots and foci analysis of time-space clustering in veterinary epidemiology techniques for analysis of disease clustering in space and in time in veterinary epidemiology prevalence of and risk factors for leptospirosis among dogs in the united states and canada: cases ( - ) serovar-specific incidence of and risk factors for leptospirosis among dogs presented to a veterinary teaching hospital geographical risk factors for leptospirosis among indiana dogs key: cord- - srvtmbn authors: brown, david title: the role of the media in bioterrorism date: - - journal: beyond anthrax doi: . / - - - - _ sha: doc_id: cord_uid: srvtmbn nan in many ways, journalism about bioterrorism is little more than a special case of journalism about science. even when a bioterrorism story involves some broad public policy issue, the subject invariably rests on a substrate of science and technical knowledge. consequently, understanding policy issues involving bioterrorism -to mention nothing of terrorist events themselves -requires knowledge of biological mechanisms, an appreciation of clinical decision-making in medicine, and a sense of how to conceptualize and evaluate relative risks. many science reporters are conversant with these subjects, but some aren't. in any case, many stories on bioterrorism are written, produced and edited by journalists unfamiliar, and often uncomfortable, with scientific subjects. scientists and policy-makers should keep this in mind at all times. like it or not, they need to realize that to make themselves clear they may have to conduct a running seminar on scientific methods, concepts and reasoning. it goes -almost but not quite without saying -that the sources of information need to be conversant in those areas themselves. of all nationally compelling news events, those involving science are the ones in which successful communication most depends on simple command of the facts. political, constitutional and national security crises may be well-served by the voice of authority, the reassuring (or beguiling) power of rhetoric, and even by the ability to deftly make a weak argument. but scientific crises -which are almost always health crises at some level -require expertise, first and above all. opinion counts for little when evaluating hazards to life, or devising a response to them. judgment and authority are useful tools only when wielded by people who know what they are talking about. this is a very hard lesson for policy makers to learn. but it is the first one they must if they want to increase the chance that the news media will do a good job. what is the importance of the news media doing a good job? of course, it is impossible to give a good answer to that. but it is possible to say how important the public thinks the media is at such times. two weeks after the first (and fatal) case of anthrax from a bioterrorism attack using the mail occurred in october, , % of americans sampled in a poll reported they were following the news of it ''very closely''. this was a level of attention equal to that seen after the events of september that year. fifty percent said the media was not exaggerating the danger of anthrax; % said it was [ ] . in the days after the first case, the office of communications at the centers for disease control and prevention (cdc), the government agency coordinating the public health response to the attacks, conducted press briefings and television interviews, wrote press releases, and took calls from the news media [ ] . (interestingly, ½ times as many calls came directly from the public - , in all). the value of a well-informed and well-treated press in such times can scarcely be overstated. even when people providing information about bioterrorism are knowledgeable about the scientific issues and experienced in talking to reporters, they would do well to keep two ideas consciously in mind. one a principle and the other an observation, these two ideas are part of the natural mental apparatus of biologists. their importance in helping guide investigations and solve problems -their heuristic value, in short -is largely unappreciated by nonscientists. a major task of any science communicator is to bring them into public consciousness and keep them there. the first is the principle (or law) of parsimony. ''one should always choose the simplest explanation of a phenomenon, the one that requires the fewest leaps of logic'' and ''the principle that entities should not be multiplied needlessly; the simplest of two competing theories is to be preferred'' are two definitions of this principle, each converging on the notion that simpler explanations are more likely to be true than complicated ones [ ] . when this principle is invoked in scientific argumentation it is often called ''occam's razor'', after william of occam ( - ), a medieval english theologian and logician. occam (whose name is a latinized spelling of ockham, his birth village south of london) criticized what he considered the unwarrantedly complex (and therefore, he thought, likely to be false) writings of his contemporaries. he wrote that when it comes to explaining things, ''it is vain to do with more what can be done with less'' [ ] . employing occam's razor is particularly important (although not infallible) in medical diagnosis, where a physician ideally should account for all the important signs, symptoms and test results presented by the case. the clinician wielding occam's razor assumes all newly appearing clinical phenomena are the result of a single disease, not the coincidental occurrence of two or more diseases. consequently, a single diagnosis that explains all the clinical findings should be exhaustively sought, and abandoned with great reluctance. parsimony has two other corollaries besides occam's razor. one is that events are likely to unfold in the future as they have in the past -that patterns and mechanisms tend to be stable and relatively unchanging over time. the other is that unusual diseases or presentations of diseases are, by definition, unusual and should not be readily invoked. this idea is captured in two admonitions nearly every physician is told at least once during his training: ''common things are still common,'' and ''when you hear hoof beats, don't think of zebras.'' in sum, the natural impulse of physicians to resist acting on wild or untested ideas runs deep -so deep, in fact, that its power may not be fully appreciated by physicians themselves. the second idea that has heuristic value in times of bioterrorism is the bell-shaped curve. it captures the observation that outcomes arising from the same events or conditions are not identical, but differ from one another in ways that can be depicted visually and understood intuitively. most outcomes are similar to one another. they inhabit the fat, or humped-up, part of the curve, and define the average. a small number, however, are quite different from the rest, either much less or much more by whatever metric is in use. those outcomes inhabit the two thin ends, or tails, of the curve. when this pattern is symmetrical on either side of the mean (or average) value it is called a ''normal distribution.'' normal distributions have specific mathematical properties; for one, the rarity of certain outcomes can be calculated. in that sense, the bell curve can be used to predict the likeliness of future events. not all biological events have a normal distribution, but many do [ ] . these two ideas -parsimony and the bell curve -are constantly at play in biology and medicine. an intuitive understanding of how the concepts operate in widely divergent biological spheres -and the ability to employ them consciously when facing new or difficult issues -may be the chief benefit for journalists in taking more-than-introductory courses in biology. when it comes to bioterrorism, however, these two concepts are important for opposite reasons. bioterrorism dilutes the importance of parsimony. that's because bioterrorism is an unnatural event even if its components -viruses, toxins, organs, medicines -are each natural and at some level behaving in familiar ways. bioterrorism creates interactions that do not occur on their own. it produces conditions of unpredictable risk; it makes vulnerable people who aren't normally vulnerable; it alters highly evolved mechanisms of transmission, distribution, and protection. the doomsday scenario of a crop-duster laying down a cloud of anthrax spores on manhattan -an event modeled by inference, if not by name, in a recent journal article -falls entirely outside the natural history of anthrax spores, human beings and manhattan [ ] . it is safe to say that previous experience with anthrax outbreaks is not likely to be very helpful in predicting the outcome of such an event, or in planning for it. unfortunately, it is hard even to predict how unhelpful the past is likely to be. on the other hand, bioterrorism tends to magnify the importance of the bell curve as an informative idea. because size of the dose, duration of exposure, mechanism of transmission, and numerous other variables are unknown and unnatural, physicians and public health officials can not easily estimate an individual's risk during a bioterror event. in particular, it is difficult to identify occupants of the left-hand tail of a bell curve that depicts exposure to a pathogen. it's hard to say with confidence who is at very low risk of becoming infected, so that tail tends to be ignored and its occupants mentally swept into the fat part of the curve for safety sake when it comes to decisions about clinical monitoring, prophylactic treatment and other interventions. however, the bell curve that represents the side effects of interventions presents a different story. the existence of the right-hand tail -occupied by the few people who suffer serious side effects of, say, a vaccination -is either tolerable or intolerable, depending on the probability of the threat being guarded against. if the threat is high, then people will tolerate side effects (or at least the risk of them). if the threat is low, they will find side effects burdensome or unacceptable. but if the magnitude of the threat is unknownis simply ''non-zero'' -then nobody can gauge whether the side effects experienced are worth the protection gained. this was the central conundrum posed by the federal government's recommendation of smallpox vaccination for certain hospital workers in [ ] . it's useful for people who determine society's response to the threat of bioterrorism (or, needless to say, an actual act of it) to explain how the importance of different regions of the bell curve changes depending on circumstances. even if decision-makers do a good job of explaining this, however, they are likely to observe the operation of yet another bell curve -namely, the one that defines what is news and what is not. news is the noteworthy event. on any given day, this is more likely to be the odd and unusual event rather than the common and expected one. if dog-bites-man is the fat and uninteresting part of the human-canine interaction, then the two tails are where the news is: the cliche´d man-bites-dog in one tail, and the pack-of-dogs-maul-man in the other tail. in practical terms, this means that even if the balance of events is well explained, the press is always going to devote more attention to the unusual, the dramatic, the damaging. thoughtful communication with journalists (and, of course, good journalism itself) can keep this natural predilection from obscuring the larger, more subtle truth of events. so how do these three things -expertise, and the ideas of parsimony and bellshaped distribution of outcomes -come into play in actual news stories about bioterrorism? there is only been one bioterrorism event in the united states that is captured national attention in recent times -the anthrax attacks of the autumn of . (the intentional contamination of food with salmonella by the rajneeshee cultists in oregon in was largely a local story [ ] ). consequently, the examples in the rest of this chapter are drawn largely from that episode of recent history. the drama was long, with many unexpected turns of event. it captured nearly every important lesson about the media and bioterrorism that is likely to arise in the future. policy makers and public health officials (and even to some extent, private medical care providers) face a difficult task when biological terrorism threats become real. without warning they are called upon to describe events, provide advice, anticipate what may happen, and offer reassurance. these jobs are especially difficult when an event has no ''natural history'' experts can look back to for help. in the early hours and days when even the general trajectory of events is unclear, the tasks can be close to impossible. it is obvious that under such circumstances, well-meaning and well-informed may give contradictory answers and advice. in order to prevent that, authorities sometimes choose to suppress information, limit access to people who know the most, or simply avoid the press altogether. all three strategies, to varying degrees, were tried during the anthrax attacks. in terms of public confidence, one of the more damaging incidents occurred the day the outbreak became news, october [ ] . tommy g. thompson, who at the time was u.s. secretary of health and human services and the titular leader of most of the federal government's civilian health workers, held a news briefing at the white house after learning of the first case. a -year-old man in florida working as a photo editor at a tabloid newspaper was diagnosed with inhalational anthrax. he was described as an outdoorsman, and thompson mentioned that ''we do know that he drank water out of a stream when he was traveling through north carolina last week.'' several further questions established the man's age, home town, and a few other details. the press conference ended this way: it's little surprise that some listeners left the briefing with the impression there was a reasonably good chance the florida case was naturally acquired, and that drinking from a stream might have been the route of transmission. it seems quite unlikely that the medical experts believed the former even at this early stage. the latter was virtually impossible given that the patient had inhalational disease and no cases of gastrointestinal anthrax had ever been reported in the united states [ ] . however, the reluctance on the part of lillibridge to provide a fuller explanation that might have appeared to erode thompson's authority -along with fleischer's abrupt termination of the briefing -guaranteed that misleading information would be reported, and that it would be attributed to a high administration official. (fleischer's unwillingness to extend the press conference may have been something akin to a reflex action. in his role as a political spokesman, leaving facts ambiguous and opinions uncertain is often the explicit goal of an encounter with reporters, and not an unfortunate outcome. however, this should never, ever be the case when the topic is scientific. science is relatively impervious to spin, and incomplete or misleading answers are easily exposed. even when there is no intention to deceive -and clearly there was none herestopping reporters from asking questions about a technical subject when they have many left to ask is done at great peril.) as it happens, news reports that day and the next generally overlooked thompson's remark about the stream. in this country, msnbc, cnn, united press international, the washington times, and the st. petersburg times appear to have been the only ones reporting it. outside the united states, the remark was noted in the times (london), the daily telegraph (london), the scottish daily record, agence france presse, and the spanish-language news service efe [ ] . if people thought there was a good chance the florida man acquired anthrax by drinking stream water, most were probably foreigners! this curious result may have occurred because thompson made his statement at the white house, where foreign news outlets have correspondents but most american newspapers don't. however, it is possible some american reporters didn't mention the remark in their stories simply because they knew it made little sense. the associated press, for example, carried a story october in which jeffrey p. koplan, director of the cdc, was paraphrased as saying ''the patient has no digestive symptoms that would indicate the anthrax came from drinking contaminated water [ ] .'' within a week, however, many newspapers -including such influential ones as the new york times, the washington post, and usa today -had discovered thompson's statement about the stream. by then nobody found the stream-contagion theory credible, and there was no evidence thompson's remark had done actual harm. nevertheless, it was publicized widely. reporters cited it as evidence in stories whose theme was the federal government's confusing and incompetent performance in communicating with the public [ ] . patricia thomas, a science journalist commissioned by the century foundation to analyze the interaction between government agencies and the press during the outbreak, observed: ''as the crisis worsened and spread, thompson never quite repaired the damage done by his off-the-cuff words about water [ ] .'' thompson [ ] .'' nevertheless, authority and candor (if that is, indeed, what it was) didn't trump credibility and expertise. while people in the bush administration apparently believed there was value in having thompson be the spokesman, he came to the event with little technical grasp of the issues -and demonstrated it immediately. as a main source of information, he was eventually moved aside in favor of various epidemiologists at the cdc, and anthony s. fauci, head of the national institute of health's national institute of allergy and infectious diseases. by then, however, considerable damage had been done in terms of public relations. the comment became one of the most memorable anecdotes of the entire outbreak. worse, it became the pocketportable symbol of what many people considered -rightly or wrongly -to be the federal government's early mishandling of the crisis. a year later, thompson's remark was still being cited, albeit indirectly, by a prominent medical journalist, lawrence k. altman of the new york times, in an article criticizing the federal government's press relations on an entirely different mattersmallpox vaccination [ ] . if having thompson be a main source of information early in the outbreak had been the only government miscalculation, then the media's overreaction to his stream comment would be especially objectionable. it was not. the cdc's press office was barely functional in the first weeks after the initial outbreak. part of this was simply the result of volume: the office counted , requests about anthrax and about bioterrorism between october and , which is likely to have overwhelmed resources under the best of circumstances [ ] . however, there were many other problems, which thomas describes well in her monograph: ''those who got in touch with a press officer were likely to be referred elsewhere. if they asked about field investigations they were advised to call local officials in florida, new york, new jersey, or washington. (there, press officers in the field sometimes bounced inquiries back to the cdc in atlanta.) reporters who asked about the search for the perpetrators were told to contact the fbi, which released prepared statements about the investigation but was otherwise tight lipped. if reporters called to follow up on comments made by secretary thompson or to ask about policy issues, they were usually referred to the public affairs office at hhs. and, although they did not realize this was happening, many reporters then had to wait while their requests were vetted by hhs officials in washington [ ] .'' the idea that cdc functions as a mere consultant to states and cities in outbreak investigations is little more than a sophistry under normal circumstances. in the anthrax outbreak, it was simply wrong. cdc was at least an equal partner everywhere it sent investigators, from the start. with the outbreak potentially national in scope and with so much attention on the federal government's response to it, for cdc spokespeople to argue that providing information naturally ''devolved'' to state and local authorities was nothing short of infuriating. (koplan believes this clarification of federal-versus-state roles in communicating with the media during emergencies is an especially important problem to solve [ ] ). providing reporters efficient access to informed sources is a tall order in a crisis, especially when events are happening in several places and many government agencies are involved. nevertheless, providing such access is a priority whose importance can scarcely be overstated. reporters can hardly be expected to abandon a subject simply because they cannot get information on it. instead, they will turn to experts who are available, but whose knowledge of events is often second-hand or whose opinions may be colored by unstated agendas. furthermore, policies that produce highly controlled and incomplete delivery of information to reporters lead to hypercritical and retaliatory journalism when things do not go well. nearly every major news organization produced a story questioning the cdc's credibility and performance in communicating with the public [ ] . regardless of how unfair some of the criticism might have been, this analysis rapidly became part of the accepted history of the event. before reflexively limiting information or routing it through a single, scripted source, government authorities should ask: to what end? what is the advantage of such regimentation? what are the hazards of letting epidemiologists, physicians and investigators speak freely and without supervision? the prime advantage (they are likely to answer) is that when only a few people are allowed to talk to reporters, the chance that contradictory versions of events, or interpretation of them, will emerge is reduced. the press seeks conflict and reports it as news; a difference of opinion is the most rudimentary and common form of conflict. however, forbidding a multitude of informed sources from talking to reporters does not eliminate conflict. it merely transforms the conflict to differences of opinion between taciturn officials and the independent experts, while simultaneously giving the public insufficient information with which to reach its own opinion -not a good combination. an excess of detail and analysis -some of it contradictory -is not likely to produce more public confusion and negative reporting (although, of course, it is impossible to say this with certainty). the second argument that officials will probably make in defense of controlling the flow of information is that such a policy does not waste the time of people who have other jobs to do. this is undisputedly true. but it is a false economy. in a true health crisis such as an attack with a biological weapon, an effective public health response and clear communication with citizens are equally important. any system that puts them in conflict or requires them to compete should be changed. reassurance, which requires little time or expertise to deliver, is no substitute for information. in fact, unaccompanied by information, or in the presence of events that continue to go badly, reassurance makes people feel isolated and suspicious. the excessive number of calming messages during the anthrax attack drew criticism even from sympathetic quarters. philip s. brachman, an epidemiologist and anthrax expert who was retired from cdc after three decades of service, was quoted in one newspaper report: ''we have an intelligent public in this country. don't treat them as children. [officials] in the beginning got up and said, 'don't worry.' that's nonsense. what i would do is say, 'we've got a problem, you have every right to be fearful, i'm fearful too, and here's what we're doing' [ ] .'' giving the media more information than it asks for or can easily digest is a safer strategy than giving the media the minimum it will tolerate or only what it can understand with no help. like anyone engaged in acts of construction, reporters are happy to have more building materials than they need. authorities should not worry that too much information will confuse. in general, reporters will seek and use only the level of detail with which they are comfortable. bad journalism is almost never the product of too many facts. the prominent science writer laurie garrett put it well: ''if you build it, we will come. if you have a valid information source that is readily available and easy to get to, with openness and facilitation, it will be used. most reporters will not search for unreliable facts elsewhere [ ] .'' at the very least, a free flow of information will disarm journalists of their principal complaint in times of crisis -namely, that the people in the know are hiding things. in a bioterrorism crisis, the cdc should consider designating a high official with scientific expertise -not a member of the communications staff -to function as a kind of rapporteur of agency deliberations. ideally, this person should have some sense of what constitutes news and a fully reported story. he or she would be relieved of regular responsibilities but would otherwise function fully as an insider in agency activities. agency officials would continue to brief the press in time-limited sessions. during the anthrax and sars outbreaks, this was done in daily or near-daily telephone press conferences lasting about an hour. however, there were almost always unanswered questions at the end. the rapporteur would remain on the line for an open-ended period to answer them, provide scientific context or background explanations, and generally seek to eliminate ambiguity and misunderstanding. this would enhance clarity and transparency. it would also require planning and institutional courage. the federal government eventually solved the problem of expertise in its communication with the press during the anthrax attacks. but the experts weren't able to end the press's -and the public's -relative lack of understanding about how the outbreak response was being conducted. over the course of the weeks between the first diagnosed case (october ) and the last (november ), spokesmen for the federal government repeatedly made assessments and predictions that turned out not to be correct. from the press's perspective, this was perhaps the most memorable -the most ''thematic'' -aspect of the entire event. the illness in the florida man was initially declared an ''isolated case'' with ''no evidence of bioterrorism [ ] .'' while indisputably true when uttered, these statements on the first day set a pattern of confident assertions overturned by events. in ensuing weeks, pronouncements that a letter containing anthrax spores had to be opened in order to release enough pathogen to cause inhalational anthrax [ ] ; that postal workers were only at risk for cutaneous anthrax [ ] ; and that ordinary citizens had nothing to fear from mail all turned out to be wrong [ ] . the fact that each successive event inscribed a circle of risk with a wider radius (and with more people in it) did not help the credibility of the speakers or their agencies. a statement by steven wiersma, florida's state epidemiologist, after the first victim died was notably different in tone and content from so much that followed: ''i don't want to give anyone the slightest inkling that we know what caused this [ ] .'' why did so many assertions turn out to be wrong? there's no certain answer. but my theory is that many smart and experienced people failed to anticipate events such as inhalational anthrax in postal workers and a nearly homebound woman because of an instinctive belief in parsimony. those things simply seemed so unlikely -without precedent, actually -that planning for them was unnecessary, and perhaps even irresponsible given the likelihood of unintended consequences and morbidities. the tracks of this thinking are evident in what several high officials said when they were queried by reporters (and others) about why they had not taken steps some believe might have saved lives. koplan, cdc director, described his and his colleagues' thinking quite clearly several times. in one of the earlier daily teleconferences with reporters, on october , he reviewed the entire sequence of events. it was a highly illuminating account of epidemiological thinking. back to this particular outbreak. i think people are somewhat surprised that we're learning things on a day-by-day basis, but that's really no different from any other investigation that we've done this year, years, or over the last years. the way the natural history of these investigations are, you always wish you knew on day -on day one what you know on day , and it's probably not going to be different here. we learn new things almost daily in this, and try to anticipate, of course, what's coming up the next day or the next week. it's obviously much more difficult when you've got a purposeful intent and someone malicious at the other end engaged in combat on this, and that is different from anything else we have done before. a little later he describes how the belief emerged that a letter had to be opened to cause inhalational anthrax, and that contact with unopened letters containing powdered bacteria could only cause cutaneous anthrax. the letters we had seen or had described to us-we didn't have the letter in hand, but the letters we had had described to us, both the one from the new york post in new york and then the next set in washington, d.c., the letter that was in the hart office building that had been addressed to senator daschle, were described to us as welltaped, meaning that the seams along that letter were taped in a way that would have minimized, if not eliminated, the ability of a powder to seep out through openings around the letter. you would have to open the letter. and, indeed, we were told that the letter that was sent to senator daschle had to be opened by a scissors because of how well it was sealed. so through this period of time we were still operating on the assumption that in order for a letter to convey this-the anthrax, it had to be either opened by someone who was opening mail, or in some way torn or disrupted in the sorting process, because the concept of a powder in a sealed letter was one that suggested that it would stay in that letter. and that was our epidemiologic experience with the cases we had seen so far. that construct obviously changed markedly with the report of inhalation anthrax in mail workers in the brentwood facility in washington where mail was not opened in the places where these individuals were exposed, or seem to have been exposed, and where the disease that they contracted was not cutaneous anthrax, which takes less spores, and is obviously less threatening than inhalational anthrax, and in which the physical characteristics are different. but to get a aerosolization of anthrax requires both air currents flowing around, and some larger quantity of smaller-sized spores to be present, and not easily explained at all by unopened mail. and with that, our current construct on the risk includes, obviously, letters that are unopened as well as letters that are open, that have had, been tampered with or have been maliciously placed in the mail with anthrax spores. [ ] the next day's teleconference featured this exchange about the possible risk from ''cross-contaminated'' letters -pieces of mail that don't themselves contain anthrax spores but which have come in physical contact with ones that do: reporter: on the cross-contamination possibility... does that mean the public is more at risk, and besides the -some different substations, are you looking at expanding the prophylaxis to perhaps whole zip codes? dr. koplan: no, on that latter; just plain no. let's get back to this issue of crosscontamination versus, you know, prim-whatever we're gonna call them-primary source criminal letters, or mailings. that where you indicated that there is an inhalation case in the state department that's been reported, i think we all think that that would be highly unlikely to virtually impossible to occur, just by cross-contamination, and as well, without having these letters in hand, but based on what we've seen in other sites, there are probably multiple mailings that have gone out, and, you know, there may be several places in the federal government that have been deemed targets for these letters to go to. so i guess my own personal working hypothesis would be that this is not crosscontamination. it just wouldn't be enough material, infectious material from crosscontamination to do that. [ ] the day after that, bradley perkins, the cdc's lead epidemiologist in the florida anthrax outbreak, was asked about why environmental sampling had not gotten down to the level of the ordinary household. reporter: can i follow up on the first part of those? what about the idea of homes? why aren't they being tested and people on cipro if they also get their mail from the same place? dr. perkins: to date the epidemiology suggests that the cases that have occurred have not occurred as a result of exposure in home settings. and that's why we're not focusing on them at the current time. if the epidemiology changes, we will-we will change along with that epidemiology. [ ] these quotations are a useful peek into the minds of two highly skilled and experienced epidemiologists. they reveal parsimony at work. they also show the unreliability of parsimony in biological terrorism, as the latter two assertions -that cross-contaminated mail, and mail received in the home would not cause inhalational anthrax -would soon prove incorrect. although the route of exposure of a non-medical hospital employee in new york city was never found, it is likely to have been cross-contaminated mail, as no spores were cultured from her workplace or home. the anthrax source in the case of a nonagenarian woman in connecticut also remained obscure, but as she rarely left her home and no gross contamination was found in it, the best inference is that she was infected by a cross-contaminated letter carrying a small number of bacterial spores. a similar failure of intelligent and parsimonious thinking can be expected in any bioterrorism event for the reasons mentioned earlier -they have few or no precedents, and are likely to defy the natural history of the disease in question. public health officials can count on being wrong much of the time. the press is likely to focus on the wrongness, and on the ''meaning'' of the errors. why? because the press's only consistent specialty is political analysis, the divination of how events affect power. the journalist james fallows has described this phenomenon: ''no one expects cokie roberts or other political correspondents to be experts on controlling terrorism, negotiating with the syrians, or other specific measures on which presidents make stands. but all issues are shoehorned into the area of expertise the most prominent correspondents do have: the struggle for one-upmanship among a handful of political leaders [ ] .'' this insight is most relevant for the media's handling of matters of foreign or economic policy, but medicine and public health are not immune. the top officials of the new jersey department of health and senior services noted this in their detailed account of the state's experience in the anthrax outbreak: ''as the situation continued, news reports focused on what decisions were made (e.g., the closing of a facility, use of antimicrobial agents) and how they were made. the media and public were interested in what the response to the event seemed to say about state decision making and readiness to address emergencies in general [ ] .'' if a journalist doesn't really understand the medical, statistical, and biological substance of a disease outbreak, he can at least appear to be knowledgeable about the interaction of individuals and agencies, and how events are believed to be changing their power and image. much of this coverage is unavoidable. some of it is even justified and illuminating [ ] . in general, though, the public is better served by reporting that tries to reveal the substance of complex events and decisions rather than interpret them. public health agencies are better served by this approach as well. there is only one way to keep attention on the substance and that is to reveal the process of decision-making to the press and public as it happens. the best chance of keeping wrong decision and incorrect inferences from becoming the main story is to vicariously allow the non-experts to experience the difficulty and uncertainty of responding to events as they unfold. this is not necessarily done by opening meetings and conference calls to the press (although letting reporters occasionally witness such events is a good idea). what public health officers and policy-makers need to do is simply describe to journalists how decisions were made. they should not wait until the decisions prove to be right or wrong before they describe the thinking that went into them. they should do it in something close to real time (which regular briefings, such as the cdc's daily teleconferences, offered). specifically, public health officials should review the choices they considered when facing a set of facts and uncertainties. they should describe what the arguments for each course of action were, directing reporters' attention to the evidence and logic that advocates for each position brought to bear. they should reveal, at least in general terms, the magnitude of disagreement and the steps that led to its resolution -if, in fact, resolution preceded decision. cdc officials did a fairly good job of describing the logic of their thinking and the process by which decisions were reached. it occurred, however, almost entirely after the fact. the prospect of following these suggestions probably would fill a public health official with horror. but it should not. people appreciate being spoken to candidly. transparency is increasingly expected in government operations. the public appreciates being treated as intelligent enough to follow a complicated process undertaken on its behalf. the press is less likely to focus on process if it is forced to face the substance in all its difficult and incomplete detail. observers of all types are less likely to invoke race prejudice, obtuseness, and bad faith -all mentioned at one point or other during the anthrax attacks -if they understand how those in authority made their decisions. furthermore, people are more tolerant of uncertainty than decision-makers believe. while officials should be reassuring and do what they can to prevent panic, they should not shield the public from disagreement or discussions of what may happen if things get worse. disagreement is likely to be uncovered soon enough, and many people's understanding of what constitutes a worstcase scenario is likely to be more frightening than anything the facts support. on the issue of the threat of public panic, the record of how people behave during mass casualty events may be instructive. the national science foundation funded a study in which epidemiologists systematically analyzed the public response to disasters that occurred between and . these included an underground gas explosion in guadalajara, mexico, that killed more than people in ; the first bombing of the world trade center in new york in ; and the northridge earthquake in california in . the findings were revealing. one of the researchers described a few of the more salient ones: overall, the evidence suggested that victims tend to respond effectively and creatively. what we saw repeatedly in disasters was that victims formed spontaneous groups that have roles, rules, leaders, and a division of labor. this is the phenomenon of emergent collective behavior talked about extensively in the literature on the social science side . . . the literature and our study show that panic is relatively rare. there's a lot of talk about panic, and there's a general assumption that the public would panic in a bioterrorism event. my question is, where does the data come from to support that? in the events we studied, we were amazed to interview victims and health care workers who commented repeatedly on the absence of panic, complaints, or irrational behavior. many emergency department workers said, ''gee, i wish things worked this smoothly all the time.'' most people talked about an eerie feeling of calm that came over people during life and death moments. panic happens in disaster movies but typically not in real disasters for reasons that probably are based in evolution. what we witnessed is that ordinary citizens are amazingly capable of avoiding deadly harm. [ ] william patrick iii, a former biological weapons worker quoted in this article also told david brown of the washington post in late october, that he had not been contacted by government investigators or epidemiologists in the weeks after the first anthrax cases. although this evidence is indirect, it suggests that if difficult decisions -and the hazards they create -are explained fully to the press and public, panic and irrational behavior are not likely outcomes. in fact, the usual assurances that things will probably be okay are more likely to seem believable if decisionmakers reveal why they feel that way and give at least a hint of how events nevertheless might prove them wrong. this strategy may improve the image of public health decision-makers during a crisis. but that is not the main reason for it. the chief benefit is that it gives the public a vicarious sense of control. knowledge tends to allay fears even when uncertainty and danger are part of the knowledge. as evidence of this, public health officials need look no farther than medicine itself. description and prognostication were what physicians chiefly did before they were able to cure -and people took great solace from that alone. it is also possible that the act of preparing to describe the logic of a just-made decision to the press may itself be a useful tool in clarifying thinking and bringing unquestioned assumptions into consciousness. one wonders, for example, whether the assumption that mail had to be opened to cause inhalational anthrax -the assumption that may have contributed to the fatal infection of workers at the brentwood postal facility -would have stood up had there been greater public scrutiny of the assumptions and arguments being made behind closed doors. after all, the first cases of inhalational disease, at the florida tabloid newspaper office, were not definitively associated with open mail, and in fact no spore-containing letter was ever found there. similarly, a somewhat more open discussion of the aerosolization potential of finely milled anthrax spores might have directed epidemiologists' attention to the researchers retired from the united states army's biological weapons program -the only people with first-hand knowledge of the issue -sooner rather than later [ ] . but even if the people who deliver information to the press are well-informed and they describe their decisions transparently, that would not guarantee that what appears in the newspaper and on television does not contain misleading information. there are crucial concepts that are second-nature to scientists but which are barely understood by the press and public. it is the job of public health officials to give the press a crash-course in these concepts. the most important one, as earlier suggested, is the usefulness of the bell-shaped curve in understanding the probability of complicated events. reporters and readers like to have concrete answers to questions. one of the more persistent queries, raised after the first case, was: how easy is it to contract inhalational anthrax? the answer was frequently given in number of spores, as inferred from experiments on monkeys. the number was often quoted; so was a range of to , spores [ ] . reporters considered this a rather imprecise answer to the question, and at some level it was. as cases of disease occurred without the recovery of infecting letters, the estimates were questioned widely in news stories, and offered as evidence of ''how little we know about anthrax.'' a knight ridder story of october , noted that an anthrax expert outside the government ''said that officials have overestimated the amount of anthrax necessary -a minimum of spores -to cause inhalation anthrax [ ] .'' at the cdc teleconference of october , a reporter asked: ''are you all doing any work in the labs perhaps with animals to test the assumption that perhaps with this particular form of anthrax it could take less than spores to cause inhalation disease? [ ] '' in fact, the estimates and the events were confusing and contradictory only if one believed there was an absolute threshold for infection. it was clear that most journalists though of infection as analogous to a light switch -a certain number of spores will exert sufficient force to turn the light on, and fewer will not. but this is rarely, if ever, the case with infections, and certainly not with anthrax. the spore numbers are estimates of the number of the dose sufficient to infect % of the people exposed -the infectious dose %, or id . half the people exposed to it won't become sick and possibly die, so it is far from being the minimum dose necessary to cause infection. because there is no minimum dose, biologists use this mid-way dose as a measuring stick for the infectiousness of something. while the usefulness of the id -and the bell-shaped distribution it implies -is not intuitively obvious at first, once it's grasped many things are easier to understand. first, it explains why precision isn't possible in describing infectious dose, and thus why imprecision of itself isn't terribly newsworthy. more important, it helps make the two most mysterious cases of the outbreak -the -year-old female hospital worker in new york city and the -year-old nearly home-bound woman in connecticut -somewhat less mysterious and frightening. that's because if there is an id , there's also an id -the dose of spores that will infect out of people. for that matter, there's also an id . -the dose that will infect in a -and an id . -the dose that will infect in , . so if it turns out that spores can get out of an envelope and stick to other envelopes, and if a fraction of those spores can become airborne again, and if there are a lot of envelopes moving around putting up spores in whatever tiny dose is the id . -then it stands to reason that someone among the thousands of postal customers will get infected. in some sense, all those envelopes are out there probing the population for the rare person who's susceptible to such a small dose. the envelopes are looking, so to speak, for the person who occupies the tail of the bell curve -because someone does occupy it. so, it should be no surprise when such a person appears [ ] . the new york city patient -a relatively healthy working woman who was not especially old -doesn't present any obvious reasons why she might have been susceptible to a small dose. but the -year-old connecticut woman clearly has the major risk factor of age and its relative immunosuppression. in addition, she had the habit of tearing envelopes in half after opening them, which would have helped reaerosolize spores deposited on the outside through cross-contamination. similar confusion surrounded the issue of whether exposed people should undergo a three-dose course of anthrax vaccine after completing a day course of antimicrobials. the large outbreak of inhalational anthrax caused by the accidental airborne release of spores in sverdlovsk, soviet union, in recorded no infections more than days after exposure [ ] . evidence from monkeys, however, suggests that infection can occur after more than days of latency [ ] . consequently, public health authorities offered vaccine, to be given along with more days of antibiotics, to a large group of people, but did not recommend that they take it. the decision, instead, was left to the exposed people themselves. this agnostic stance was widely criticized -perhaps with good reason -as being insufficiently clear and authoritative. a new york times editorial called it ''an unsatisfactory medical cop-out,'' and added: ''it is disappointing that officials who are in the best position of anyone to make sense of the admittedly sparse data on anthrax are throwing up their hands and leaving the decision to patients and doctors who have far less command of the subject [ ] .'' however, the key piece of data informing any individual's decision was not in the possession of the experts. that piece was the individual's tolerance of risk. what to do depended on whether a person worried about being one of the few people (actually, monkeys) in the tail of the bell curve and wanted to do something about it, or whether he assumed he was in the fat part of the curve where most people reside and was willing to live with the slim chance he was wrong. it is a subtle point -but one that has the advantage of being a statement of reality. public health officials could have helped the press and public understand the ''unrecommended offer'' of vaccine better if they had explained it as yet another decision arising from an understanding of the bell curve -the orderly distribution of events in biological systems in which there are many more average events than exceptional ones. the suggestion that such a concept could be taught to dozens of reporters on the fly isn't entirely far-fetched. journalists are used to getting one-on-one telephone tutorials from experts; it's one of the chief privileges of the profession. daily teleconferences with scientists and public health officials -the only reasonable way to manage news distribution during a bioterrorism eventprovide the opportunity. the internet even makes it possible for someone announcing a decision to help explain it with a diagram or graphic. at the moment, using the internet to provide journalists with background information during a running news story such as the anthrax outbreak is almost entirely untapped. if there is another event like it, public health officials would be wise to at least post on an easily accessed site a dozen or so scientific papers that form the core evidence base for the disease in question. posting the core literature would have many advantages. it would show how information was acquired through observation, experimentation, and extrapolation. it would demonstrate how some interventions (such as the use of anthrax vaccine after human exposure to the bacterium), while ''experimental'' in a formal sense, is grounded in evidence and not likely to carry much of the uncertainty associated with experimental therapies as commonly understood. it also provides color. the description of the investigation into an anthrax outbreak at a dickensian goat-hair mill in manchester, n.h., in the s was both fascinating and informative [ ] . the fact that those epidemiologists swabbed anthrax spores off the factory president's desk -which one of the still-living investigators told me -revealed something about the cohabitation of man and spore at all levels of that industry. the relationship between medicine and the media has never been especially easy or sympathetic [ ] . medicine values privacy and authority. the media seeks to publicize the private and is reflexively suspicious of authority. medicine values nuance and caveat in communication. the media relishes definitive statements and often cannot tolerate subtlety. medicine generally attempts to reassure. the media often seeks to present facts in the most arresting and frightening context that can be defended with claims of technical accuracy. the hostility between the two worlds is sometimes profound. the twentiethcentury embodiment of medicine's ideals, william osler, said with more than a little bitterness: ''believe nothing that you see in the newspapers -they have done more to create dissatisfaction than all other agencies. if you see anything in them that you know is true, begin to doubt it at once [ ] .'' on the other hand, the media does not do a bad job. on promed-mail, the main public website for breaking news in infectious disease epidemiology, about % of the postings ''start with a raw newspaper article.'' in an analysis of months of activity, . % of outbreak reports from unofficial sources -mostly newspapers -turned out to be wrong. that compared favorably with a . % rate of inaccurate reports from official health agencies [ ] . as an independent and occasionally unruly force, the media also has an invaluable role in emergencies, including epidemics. this was noted by numerous observers during the outbreak of severe acute respiratory syndrome (sars). in china, where control of the disease had consequences for the entire globe, the world health organization provided important assistance to local authorities, but ''it was the press that kept the focus on and led to the resolute responses that occurred,'' according to one western observer [ ] . the lessons from the anthrax outbreak were evident soon after it ended. for sandra mullin of the new york city health department, they were similar to ones another disease had just taught. the media blitz surrounding the anthrax situation in new york city and elsewhere has far surpassed the crush of . nonetheless, west nile provided a drill of sorts for the challenge public health is now facing. we learned most importantly about the need to address perceptions of risk, to have credible communicators, and to get information out in a timely and consistent way. in the past few weeks, this has meant getting facts out to the public rather than inventing ways to reassure the public. it has also involved acknowledging the seriousness of bioterrorism, but at the same time pointing out that thus far the morbidity and mortality associated with it are far surpassed by preventable illnesses like influenza and human immunodeficiency virus (hiv). admitting when we do not yet have the answers has also been required. [ ] they're likely to be the lessons learned next time, too. the pew research center for the people and the press, poll released oct box - . communicating about anthrax: some lessons learned at the cdc the first definition is from principia cybernetica guides for the perplexed physician discussions of the bell-shaped curve and normal distribution can be found at numerous websites, including at the university of the sciences in philadelphia emergency response to an anthrax attack the former head of the global smallpox eradication campaign and now the bush administration's main adviser on smallpox matters, told the committee [advisory committee on immunization practices] that the risk of the disease's reappearance is no different now from what it was when the panel last met toxic terror: assessing terrorist use of chemical and biological weapons the anthrax attacks, the century foundation other corynebacterial infections, and anthrax, in harrison's principles of internal medicine th edition accessed through lexisnexis with search terms: ''thompson'' and ''anthrax'' and ''stream'' and ''north carolina florida man in critical condition with rare form of anthrax, raising fears about terrorism government's anthrax muddle: many voices, few facts bioterrrorism: preparedness and communication, delivered sept at the health department, the messengers still stumble but there probably should be a more obvious federal presence earlier where your suspicion has gone up. if it's anthrax or q fever or plague, that would be examples. sure, you could have the state of florida officials taking questions, but also make sure that we make some comments from a national perspective terrorism challenges thompson; pilloried, praised for crisis handling, he's still determined terrorism challenges thompson; pilloried, praised for crisis handling, he's still determined understanding media's response to epidemics statements to this effect were made by both jeffrey koplan and julie louise gerberding of the cdc in the cdc teleconference florida man suffering from anthrax dies why americans hate the media, the atlantic lessons from the anthrax attacks of : the new jersey experience ttrial and error: seven days in october spotlight weakness of bioterror response; health officials were slow to grasp anthrax hazard for d.c. postal workers; mad dash from brentwood the word ''emergent'' in the third sentence is used in its correct sense, meaning ''unexpected and suddenly appearing,'' and not to denote action done quickly and under emergency conditions experts' key lessons on anthrax go untapped; fort detrick's veteran researchers studied bioweapons for years future cases of anthrax, clues from decontaminated letters will help investigators the anthrax trail: tracking bioterror's tangled course the sverdlovsk anthrax outbreak of industrial inhalation anthrax a muddled message on anthrax vaccine an epidemic of inhalation anthrax, the first of the twentieth century medicine and the media: a case study sir william osler: aphorisms from his bedside teachings and writings global awareness of disease outbreaks: the experience of promed-mail learning from sars: preparing for the next disease outbreak'' workshop sponsored by the institute for medicine public health and the media: the challenge now faced by bioterrorism key: cord- -rep ly authors: tang, chen; wang, tiandong; zhang, panpan title: functional data analysis: an application to covid- data in the united states date: - - journal: nan doi: nan sha: doc_id: cord_uid: rep ly the covid- pandemic so far has caused huge negative impacts on different areas all over the world, and the united states (us) is one of the most affected countries. in this paper, we use methods from the functional data analysis to look into the covid- data in the us. we explore the modes of variation of the data through a functional principal component analysis (fpca), and study the canonical correlation between confirmed and death cases. in addition, we run a cluster analysis at the state level so as to investigate the relation between geographical locations and the clustering structure. lastly, we consider a functional time series model fitted to the cumulative confirmed cases in the us, and make forecasts based on the dynamic fpca. both point and interval forecasts are provided, and the methods for assessing the accuracy of the forecasts are also included. study, our data are collected at state level (see section for details), with the following research questions in mind: ( ) does the practice of public health measures (e.g., social distancing and mask wearing) help to mitigate the spread of the covid- ? on the other hand, does the reopening of business exacerbate the spread of the disease? ( ) is there any quantitative way to understand the correlation between infections and deaths caused by the covid- in the us? does the correlation vary from state to state? ( ) is the spread of the covid- related to the geographical locations of the infected regions or hot spots (at the state level) in the us? ( ) is there a way to have some reasonable forecasts with regard to the total number of confirmed cases nationwide? we collect the number of confirmed and death cases of the covid- from the continental states in the us between / / (the date of the first domestic confirmed case reported in the us) to / / (the weekend before school reopening in most of the states). the data of cumulative confirmed and death cases were collected at state level, from a publicly available repository released and updated by new york times (https://github.com/nytimes/ covid- -data) . in what follows, the daily confirmed and death cases are obtained effortlessly. the majority of our analyses is done at the state level. noticing the significant differences in the population size for each state, we standardize the data, using the estimated population size for each state at the end of year from the us census bureau (https://www.census. gov/popclock) to scale all collected data (cumulative and daily cases), and save them in units of "per million". in figure , we plot the number of daily confirmed and death cases in the us. from early may to early june, the cumulative case-to-fatality rate (cfr) of the covid- in the us has stayed consistently high around . %, close to the estimate ( . %) given in [ ] , which is slightly higher than the cfr in wuhan, china ( . %) reported on / / [ ] , and significantly higher than the global cfr ( . %) according to who director-general's opening remarks at the media briefing on / / . in august, the cfr in the us has declined to . %. one important epidemic metric for the study of the infectious disease dynamics is the basic reproduction number, usually denoted as r . it refers to the average number of secondary cases per infectious case in a population where all the individuals thereof are susceptible to the infection. a variant called the instantaneous reproduction number, denoted as r t , is the average number of cases generated by each infection at a given time t. we observe that of continental states in the us has had r t > (https://rt.live) on / / , suggesting that the epidemic has not yet been fully contained by the end of may, . in fact, this proportion climbs to out of in the following month. upon the end of the study period, the proportion of the states with r t > has dropped to out of , but the whole nation is still faced with the potential risk of a massive spread owing to the reopening of schools in the fall. some other results of critical epidemic characteristics and dynamics of the covid- in the us have been reported in [ ] . in this study, we treat the collected data as functional data, and adopt methods from the functional data analysis (fda). figure shows the functional data of daily confirmed and death cases (per million) of the top five states in the us during the study period. as discussed in [ ] , the fda methods are applicable to sparsely and irregularly spaced data in time, so are preferred to the standard time series methods in the analyses of the time series data. besides, the fda methods manage to capture the functional behavior of the underlying data which generate the process (see [ , , ] for details), and have been widely adopted in a plethora of applications in public health and biomedical studies [ ] . in the next few sections, we list the adopted fda methods, and present the analysis results when they are applied to the covid- data in the us. in multivariate statistics, modes of variation are a set of centered vectors describing the variation in a population or sample. typically, variation patterns are characterized via the standard eigenanalysis, i.e., principal component analysis [ ] . analogously in the fda, modes of variation provide an efficient tool to visualize the variation of the functional curves around the mean function. identifying modes of variation in functional data is usually done through the functional principal component analysis [ ] , providing new insights and precise interpretations of the functional data. . . functional principal component analysis. consider a probability space (r + , f, p), and a compact interval i ⊂ r + . a stochastic process x(·) is called an l process on i if let x i , for i = , , . . . , n, be independent realizations of the underlying l process x(·). by convention in the fda, functional data are given as for t ∈ t i := {t ij , j = , , . . . , n i }, a time schedule for subject i. the terms ε i (t ij )'s are independent measurement errors with e(ε i (t ij )) = and var(ε i (t ij )) = σ ij for some constant σ ij . the functional principal component analysis (fpca) is a powerful tool for dimension reduction in the fda [ ] . in essence, fpca is an expansion of the realization x i (t) into functional bases consisting of the eigenfunctions of the variance-covariance structure of the process x(·), where the eigenfunctions are required to be orthogonal. let {φ k : k ≥ } denotes the collection of orthogonal eigenfunctions. in addition, let µ(t) = e(x(t)) be the true mean function, and ξ ik := i (x i (t) − µ(t))φ k (t) dt be the k-th functional principal component (fpc) of x i (also called scores in the jargon). by the karhunenloève theorem [ , ] , we have due to the difficulties in estimating and interpreting the infinite sum in equation ( ), a conventional treatment is to approximate it by a finite sum of k terms. in what follows, we set where υ i (t) is the counterpart of ε i (t) in equation ( ) owing to truncation. we refer interested readers to [ ] for a comprehensive review of the fundamental theory of fpca. one primary application of fpca is to explore modes of variation [ ] for the functional data, reflecting the percentage of total variations contributed by each principal eigenfunctions. when applying the fpca method to the covid- data of the continental states in the us, we notice that they are not identical in time schedules. the identification of the first covid- case may differ by as long as days across the country. having observed the sparsity in the functional data during the early stage of the outbreak, we adopt the principal components analysis through conditional expectation (pace) approach proposed in [ ] for our analysis. the estimation of the fpc score of y i = (y i (t i ), . . . , y i (t in i )) t , for i = , , . . . n, via pace takes the following major steps: ( ) for each y i , estimate the mean function µ i = (µ(t i ), . . . , µ(t in i )) t and the covariance structure Σ y i = cov(y i , y i ) by locally linear scatter and surface smoothers, respectively [ ] ; ( ) discretize the off-diagonal smoothed covariance to estimate the eigenfunctions φ ik = (φ k (t i ), . . . , φ k (t in i )) tc , k = , , . . . k, and the corresponding eigenvalue λ k [ ] ; ( ) adopt an akaike information criterion (aic) type criterion to select the number of eigenfunctions, i.e., k, needed to approximate the process [ ] ; ( ) lastly, the estimation of the fpc score for the i-th subject is given through the conditional expectation:ξ whereλ k ,φ ik ,Σ y i andμ i are respectively the estimates of λ k , φ ik , Σ y i and µ i . in practice, the r package fdapace [ ] allows us to apply the pace method to the functional covid- data directly. the computation results and corresponding discussions are given in the subsequent section. to begin with, we plot the fitted mean curve (which estimates the trend over time), the fitted variance curve (which estimates the subject-specific variation) and the fitted covariance surface of daily confirmed cases across continental states in figure . the estimated mean is close to in january and february, and starts climbing since early march until reaches a local maximum in late april. the overall trend in may is downwards, followed by a second wave that starts from june. the curve hits the peak at the end of the third week of july. the estimated variance curve looks similar to the fitted mean curve in shape, which stays low at the very early stage, and deviates from at the end of the first week of march. the first local maximum emerges around / / , and then starts decreasing until / / . the global maximum of the curve is observed in the third week of july, corresponding to the worst period of the attack of the covid- to the country. the correlation surface is presented through a contour plot. measurements at close time points appears to be highly correlated. the correlation between early and very late times are close to , whereas that between early and middle times tends to be negative. the correlation patterns among middle and later times are slightly negative. in particular, the correlation surface reveals that the increase in the number of confirmed cases follows three different stages, where the two break points are respectively / and / . the strong positive correlation seems more persistent in the latter two stages. next we apply the pace method to the covid- data of daily confirmed cases in the us. the adaptive algorithm selects a total of six eigenfunctions (accounting for more than . % of the total variation), where the first two together explains about % of the total variation of the data (see figure ), indicating the remaining eigenfunctions are less important. the first eigenfunction (accounting for . % of the total variation) remains constant close to during the first month of the study period, and starts decreasing afterwards. the value of the eigenfunction falls negative since / / until it reaches a local minimum around / / . after that, the function value keeps increasing until it hits the peak around / / . the first eigenfunction defines the most important mode of variation, suggesting that the state-specific intercept term captures the vertical shift (especially later times) in the overall mean. besides, the first eigenfunction reflects a contrast between middle and late times, where the break point emerges about one week after the announcement of business reopening in the majority of the states in the us. the second eigenfunction presents a variation around a piecewise linear time trend. the value of the eigenfunction is negative at early times, and becomes positive since march, and hits a break point in the third week of april. since then, it begins to decrease but stays positive during the rest of the study period. the second eigenfunction suggests that the second largest variation among the states is a scale difference along the direction of this functional curve. in statistics, canonical correlation analysis is a tool to make inference based on the crosscovariance matrix of multiple datasets. the analogue in fda, named functional canonical correlation analysis (fcca), aims to investigate the correlation shared by multiple functional datasets [ ] . specifically, here we use the fcca method to quantitatively estimate the correlation between confirmed and death cases across the states. functional canonical correlation analysis. we first outline the theoretical setup of the analysis method [ , ] , and refer the interested readers to [ ] for a concise review. let x(·) and y (·) be two l processes on two compact intervals, i x and i y , respectively. in addition, let h (i) denote the hilbert space of square-integrable functions on some compact interval i, with respect to lebesgue measure. in addition, the notation ·, · refers to the standard operation of inner product. by definition, the first canonical correlation is given by the pair of the optimal solutions (u , v ) are called the canonical weight functions of ρ . for k ≥ , the k-th canonical correlation coefficient, denoted ρ k , is defined under the condition of orthogonality: set ρ k , k ≥ , and its associated weight functions (u k , v k ) in an analogous way: subject to condition ( ). in fda, the inner products u, x and v, y corresponding to weight functions u and v are called probe scores. typically for k ≥ , we refer to (u k , v k ) as the canonical weight pair that optimizes the canonical criteria for ρ k . the fcca approach, in essence, determines the projection of x in the direction of u k as well as that of y in the direction of v k , such that their linear combinations are maximized for k ≥ . consider three kinds of variance and cross-covariance operators Σ xx : , which correspond to the variance structure of x, the variance structure of y and the cross-covariance structure between x and y , respectively. we then rewrite the definition expression of ρ as follows: similar arguments can also be applied to ρ k , k ≥ , by accounting for the condition of orthogonality. a standard procedure for the change of basis in equation ( ) implies that the problem is equivalent to an eigenanalysis of Σ , a maximization problem of rayleigh quotient. in this study, we use functions from the r package fda [ ] to implement the fcca method based on an integration of an exceedingly greedy procedure and an expansion of the functional basis. a variety of methods solving the optimization problem of functional canonical correlations have been developed in the literature; see for example, [ , , , ] . prior to estimating the functional canonical correlation between confirmed cases and death tolls in the us, some additional pre-processing procedures to the data are necessary, as we observe that the date on which the first confirmed case is reported varies significantly across the states, and the number of death counts stays relatively low during the entire study period in several states. canonical correlations between confirmed and death cases. now we inspect the functional canonical correlation between confirmed and death cases from the continental states in the us. the first step is to pre-process the data. noticing that diagnostic tests (e.g., swab test) of the covid- have not been widely implemented in most states until late march (for instance, the first drive-through covid- testing site in philadelphia was not open to the public until / / ), we reschedule the starting date of study period to / / for the rest of the study in this section. besides, the cumulative number of (scaled) confirmed and death cases (instead of scaled daily numbers) are used for the analysis so that no state is excluded due to sparsity, especially for those with few cases reported during april and early may. in the literature, there are several different options of basis functions for the basis expansion in the fcca. having observed some periodic features in our functional data, we choose the fourier basis here. the first canonical correlation is . , which reveals a dominant pair of modes of variation that are highly positively correlated. the corresponding canonical weight functions are plotted in figure . the canonical weight function of confirmed cases resembles a sinusoidal function with a period of one month approximately, while the counterpart of death cases seemingly contrasts early and middle times to late times (primarily in july). a state has a negative score with a large absolute value on the canonical weight of confirmed cases if it has a large number of confirmed cases in april, late may and early june, but small counts in july and early august. also, a state has a high positive score on the canonical weight of death cases if it has more death cases in july than any other time during the study period. next we plot the canonical variable scores for the death cases against confirmed cases in figure , where we see that the new york state lies on the bottom left corner. this is due to the fact that the new york state (especially new york city) has a lot of confirmed and death cases at the early stage of the pandemic, but later the transmission of the virus has been well controlled since july, thanks to the complete shutdown of the city as well as the rigorous adherence to public health measures, e.g. the practice of social distancing, mask wearing and the limit of the number of people allowed in essential businesses. since july, less than deaths has been reported daily in new york city, in contrast with an average of more than deaths every day in april. therefore, both canonical variable scores remain low in the state of new york. another "outlier" is new jersey, which is geographically adjacent to new york state. the overall trends of confirmed and death cases in new jersey are similar in shape to those in new york, but both are smaller in magnitude. therefore, new jersey sits close to new york in figure . three states in the middle with negative scores in both canonical variables are massachusetts, connecticut and rhode island, all of which are geographically close to new york. all other states are mostly scattered on the top right corner in figure . the one sits at the most top right is texas, with positive scores in both canonical variables. the confirmed and death cases in texas are not the largest in the first wave of outbreak (i.e., april and may), but the state has seen a large surge in the daily confirmed and death cases since late june. consequently, both of the canonical scores of texas remain positive. in fact, texas has controlled the spread of the disease well in april when a -day self-quarantine has been mandated, all nonessential businesses are closed, and ordered travel restrictions have been instituted between texas and louisiana (an outbreak occurs in new orleans during that period). however, with the stay-at-home order lapsed in may, and the reopening of the economy started in june, texas has experienced a huge increase in the covid- cases, due to the increasing frequencies of indoor and outdoor gatherings in large groups of people without proper public health measures implemented. clustering is another common tool for data exploration in multivariate statistics, aiming at constructing homogeneous groups (called clusters) consisting of observed data that present some similar characteristics or patterns [ ] . in contrast, observations from different groups are expected to be as dissimilar as possible. the functional cluster analysis (fca) is an unsupervised learning process for functional data. in this section, we investigate the cluster structure in the us based on cumulative confirmed cases (after being scaled) across the states. . . methods for functional cluster analysis. two classical methods for the fca are hierarchical clustering [ ] and k-means clustering [ ] . more recently, many clustering methods extended from them were proposed. see [ ] for a summary. traditional k-means clustering methods for the fca, e.g. [ ] , require a finite set of prespecified basis functions in order to span a functional space, and assume the observed functional data to admit the basis expansion. the fca is then completed by applying the standard k-means algorithm to the estimated basis coefficients. alternatively, one may replace basis coefficients with fpc scores (i.e., ξ ik 's in equation ( )) for conducting the cluster analysis [ , , ] . in modern fda, there are two methods that are extensively popular to conduct the fca. one approach is the em-based algorithm [ ] , which assumes a finite (say k ∈ n) mixture of gaussian distributions. the model is given by where θ = {π , . . . , π k , µ , . . . , µ k , Σ , . . . , Σ k } is a collection of parameters; for each c = , , . . . , k, π c ∈ ( , ) is the mixing proportion such that k c= π c = , and ψ(x | µ c , Σ c ) is a gaussian distribution with mean µ c and variance Σ c . the log-likelihood of the model in equation ( ) is optimized by the em algorithm [ ] . the setups of the e-step and the m-step are standard, available in a variety of articles, texts and tutorials, e.g. [ ] . given the number of clusters k, the em algorithm partitions a set of n observations x = {x , . . . , x n } into k clusters by maximizing the following expression: the alternative is the k-centers functional clustering (kcfc) algorithm proposed by [ ] , using the subspace spanned by the fpcs as cluster centers. this approach is popular as the distributional assumptions are relaxed. nonetheless, there are limitations in both algorithms. the kcfc algorithm assumes equal within-cluster variance, whereas the em algorithm assumes a mixture of gaussian distributions. relevant discussions on the difference between the two algorithms are included in [ ] . in the present analysis, it seems inappropriate to assume equal within-cluster variance, so we adopt the model-based em algorithm, which is available in r package emcluster [ ] . since the method is based on the em algorithm, it is critical to select the initial values of the parameters appropriately. specifically, we adopt a strategy developed in [ ] for the initialization of the algorithm, with corresponding functions available in emcluster. cluster analysis results. similar to the fcca part, we trim the study period to " / / to / / " as few (or even no) confirmed case has been observed in many states before april. the implementation of the emcluster algorithm requires the predetermination of the number of clusters in prior. there are a couple of standard methods to obtain an optimal value of k. we select the value of k via the elbow method based on the sum of squares of the within-cluster variations. the computation reveals that the most appropriate value of k is , and the optimal clustering strategy associated with k = is given in figure . the first cluster includes new york, new jersey and illinois, the three states that have been most severely attacked by the covid- in the first wave, as well as florida, texas and california, all of which have experienced a huge surge in both confirmed and death cases in the second wave. overall, these six states are the worst hit by the covid- throughout the study period. the second cluster contains states, including georgia, north carolina, massachusetts, pennsylvania and washington, etc., most of which are geographically close (but not necessarily adjacent) to the hot-spot regions. some states, e.g. georgia, north carolina and colorado, actually have reached the peak of the covid- cases in the second wave after the reopening of the business, when some mandatory protocols have been called off. besides, with the relaxation of travel restrictions, an increase in population movements may also cause the cross infections among the residents in these states. the state of washington, located at the northwest corner, also belongs to this cluster, where the first case in the us has been reported. the third cluster only has two states: utah and arkansas. utah is not directly adjacent those epidemic centers specified in the first cluster. the control of the covid- remains reasonably well in utah, and we speculate some possible reasons as follows. though there is no evidence that youngsters are not likely to be infected, they are likely to have stronger immune systems (than elders). utah has the lowest percentage of residents above in the nation. besides, utah is among the healthiest states in the nation overall (https://www.americashealthrankings. org). the attack of the covid- to the other state in the third cluster, arkansas, has also been less serious during the second wave, although it is right next to texas. the local government has maintained a series of policies that help reduce the spread of the disease, for example, the delay of school opening. the fourth cluster contains oklahoma, kansas, nebraska and kentucky, where the major industries are agriculture, core mining, and aviation, etc. besides, there are not too many tourist resorts in these states triggering large population movements. it is also necessary to note that the population densities are relatively small in these states. hence, they are less affected by the covid- compared to those in the first three clusters. lastly, a total of states are classified in the fifth cluster, including vermont, new mexico, alaska, montana, and wyoming, etc. these states are the least attacked by the virus. although the data has been scaled, most of these states are large in their geographical sizes, leading to low population densities. in fact, among all states, alaska, montana and wyoming have the three lowest population densities in the nation. for comparison, we also conduct an analogous analysis on a truncated study period from / / to / / , around which business reopening starts over a large number of states. the clustering results are presented in figure , and the cluster structure appears to be greatly different from that given in figure . essentially, the new york state and its neighbors are the epidemic centers for the period from / / to / / , and the alterations in the cluster membership flag the significant impacts of reopening the business in accelerating the spread of the virus. when forecasting the covid- data using functional data approaches, we need to preserve the temporal dynamics among curves to maintain the forecasting ability, which leads us to the context of functional time series [fts, ] . one treats an fts as a segmentation of an almost continuous time record into natural consecutive intervals, such as days, months, or quarters. this is a conventional treatment for financial data [ ] . the other treats it as a collection of curves over a time period, where the curves are not functions of time; see [ ] for example. the major difference between these two formations is whether the continuum of each function is a time variable. in this section, we start with the number of nationwide cumulative confirmed cases of the covid- in the us, where we define and convert the fts using the first convention outlined above. based on several reports on the covid- pandemic [ , ] , the average incubation period of the coronavirus is about days, but the incubation period could last up to days for most of the cases. therefore, we segment the number of cumulative confirmed cases into curves with time intervals of days. in line with the conventional treatment that segments a continuous curve into small intervals, we set the last value in one curve equal to the first value of the next. similar to the classical time series modeling, it is critical to appropriately handle the nonstationary data when modeling the fts. to circumvent the issue of the non-stationarity in the covid- data, we exploit the ideas from the literature dealing with fts of share prices. in [ ] , the authors define the cumulative intraday returns (cidr's), and later in [ ] , a formal test that justifies the stationarity of cidr's curves has been developed. here we convert the non-stationary cumulative confirmed case counts into stationary curves by calculating the daily growth rate in each curve: r n,j = × ln c n,j − ln c n,j− , where c n,j denotes the number of confirmed cases on the j-th day of the n-th segment, for j ∈ { , , . . . , }, and n ∈ { , , . . . , n }. let r n (t) be the daily growth rates curve of the n-th segment, but values can only be observed at discrete time points j, such that r n,j = r n (t j ). under the functional data framework, we assume the neighboring grid points are highly correlated, and smoothing serves as a tool for regularization, such that we borrow information from the neighboring grid points [ ] . when applying to the daily growth rate for the cumulative confirmed cases, we assume that the underlying continuous and smooth function y n (t) is observed at discrete points with smoothing error n (t j ): r n (t j ) = y n (t j ) + n (t j ); see [ ] for details on smoothing. after applying the test from [ ] , we find that the p-value is equal to . , suggesting the stationarity of the fts with respect to the daily growth rates. the rainbow plot proposed in [ ] is effective in the visualization of the fts. in a rainbow plot, functions that are ordered in time and colored with a spectrum of rainbow, such that functions from earlier times are colored in red, while the most recent ones are in violet. the rainbow plot captures the features of an fts in two ways. within each curve, the mode of variation reflects the pattern of the curve, and the ordering in color reveals the temporal dynamics over time. figure presents the rainbow plot of both unsmoothed (left) and smoothed (right) growth rates of the cumulative confirmed cases of covid- in the us from / / to / / , leading to exactly functional curves. from figure , we observe that all the curves share a similar temporal pattern, where the growth rate increases rapidly within the first four days, and then tapers off gradually. this coincides with a scientific finding that an infected person is most contagious early in the course of their illness [ ] . based on the color ordering in the rainbow plot, we see that the growth rate declines gradually from april to june, indicating the effectiveness of the practice of public health measures (including lock down policies implemented at the early stage of the outbreak), but it bounces back up again in july, flagging the effects of reopening. in the rest of this section, we develop a forecasting scheme by considering a dynamic fpca method that accounts for the temporal dynamics of the long-run covariance structure of the fts. the forecasting is done through the dynamic fpca scores. we use the root mean squared forecasting error and a nonparametric bootstrap approach to assess the accuracy of point and interval forecasts, respectively. we then apply the proposed scheme to forecast the number of confirmed cases in the us in the next days (the first day of the -day prediction segment coincides with the last day of the study period). . . dynamic fpca. the major critics of classical fpca (c.f. section . ) stem from its incapability of making forecasts as it only aims to reduce the dimension of data by maximizing the variances explained by eigenfunctions. the dynamic fpca, however, manages to reduce dimension towards the directions mostly reflecting temporal dynamics [ ] . to better accommodate the need of capturing the temporal dynamics among the fts and making better forecast, we here adopt the dynamic fpca method [ ] . the primary difference between classical and dynamic fpca is that in performing the eigenanalysis, we replace the variance-covariance function with the long-run covariance function. for an fts, the long-run covariance function, which is the functional analogue of the long-run covariance matrix in standard time series analysis, plays an important role in accommodating the temporal dependence among functions. we now give the definition of long-run covariance function. let {y i (τ ), i ∈ z} denote a sequence of stationary and ergodic functional time series, with τ being a bounded continuous variable. the long-run covariance function of {y i (τ ), i ∈ z} is given by where γ i (s, t) = cov(y (s), y i (t)). in practice, we need to estimate c(s, t) via a finite sample, i.e. {y i (τ ), i = , , . . . , n} for some integer n < ∞. we use the lag-window estimator proposed by [ ] to estimate the long-run covariance function c(s, t): where k(i/h) is a kernel function assigning different weights to the auto-covariance functions with different lags, and the parameter h is the bandwidth [ ] . typically, we assign more weights to the autocovariance functions of small lags and fewer to those of large lags. here we use the "flat-top" type of kernels, as they provide smaller bias and faster rates of convergence [ ] . for k < , the flat-top kernel is given by the selection of the bandwidth crucially affects the accuracy of estimation. here we adopt an adaptive bandwidth selection procedure [ ] to get an approximately optimal bandwidth for the subsequent estimation of the long-run covariance of fts. the estimator γ i (s, t) is given by the dynamic fpca is done through the karhunen-loève expansion exactly the same as equation ( ), but the eigenvalues and eigenfunctions are estimated based on the eigenanalysis of c(s, t). we use m functional observations to get an -step-ahead forecast by the method developed in [ ] . note that applying a univariate time series forecasting method to the score vector ξ (m) k = { ξ k , ξ k . . . , ξ mk } gives the estimated ξ m+ | m,k , then the estimate of the -step-ahead forecast is given by where µ(t) and { φ k (t), k = , , . . . , k} denote the estimated mean and fpcs, respectively. for the application to the covid- data, we forecast the daily number of the cumulative confirmed cases by the grid points on the forecasting curve. without loss of generality, we consider the one-step-ahead forecast (i.e., = ). note that this procedure generates daily forecasts up to days, since by our assumption on the fts conversion in section . , the first grid point on the curve is the same as that on the last day of the study period. by implementing the fts converting procedures from . , we obtain an fts object consisting of functional curves. we create an expanding window analysis framework, and apply the proposed forecasting method to get multiple one-step-ahead forecasts on the growth rate curve. the details are deferred to section . . . . . forecast accuracy evaluation. in this section, we introduce the methods that assess the prediction accuracy for point and interval forecasts. to make forecast for the number of confirmed cases in the us in the next days, we set = throughout the section. . . . point forecast. for a point forecast, we use the root mean square forecast error (rmsfe) to evaluate its accuracy: where n is the total number of segments in the fts, m is the number of curves used in forecasting, c m+ (j) is the number of confirmed cases at the j-th point on the (m + )-th curve, and c m+ (j) is the corresponding forecast value. the rmsfe measures the discrepancy between the forecast and the actual value. given that there are functional curves in the study period, we start with the first n = curves to generate one-step-ahead point forecasts, and repeat this forecasting procedure by adding one curve at a time until the first curves are included, which gives us (n − n = ) one-step-ahead forecasts in total. in other words, for each time point j, there are three forecast values. we choose n = as our starting point to ensure that an adequate number of curves are used for forecasting. we adopt a standard forecasting approach through the autoregressive integrated moving average (arima) model as a competing method. the forecasting results are presented in figure , where the y-axis is the average of the rmsfe (scaled by ) of the three one-step-ahead point forecasts. we observe that the mean values of the rmsfe of fts forecasts are consistently smaller than the counterparts of standard arima, suggesting that the proposed fts method is preferred. figure . average rmsfe values (scaled by ) for the fts and the standard arima method for the next days. the fts method consistently outperforms the standard arima. note that the rmsfe curve starts from , corresponding to the assumption in section . that the first day of the -day prediction segment coincides with the last day of the study period. to better capture the uncertainty of point forecasts, we construct the associated prediction intervals in this section. in [ ] , uniform prediction intervals are generated using a parametric method, and later [ ] suggests constructing pointwise prediction intervals via a nonparametric bootstrap method. the construction of the prediction intervals is based on in-sample-forecast errors, i.e., e m+ | m (j) = c m+ (j) − c m+ (j). specifically, we generate a bootstrap sample (with replacement) of forecasting errors to obtain the upper and lower bounds, respectively denoted by η ub (j) and η up (j). then we choose a tuning parameter, δ α , such that the one-step-ahead (pointwise) prediction interval is given by we use the interval scoring rules [ ] to evaluate the accuracy of the pointwise interval forecasts. the interval score for the pointwise interval forecast (c.f. equation ( )) at time point j is given by where {·} represents a standard indicator function, and the level of significance, α, is conventionally set at . . a lower interval score suggests that the interval forecast is more accurate. the ideal scenario is that the actual values of c m+ (j) values lie between c lb m+ (j) and c ub m+ (j) for all j. the mean interval score over (n − n) one-step-ahead forecasts becomes . . . future forecasts. we apply the proposed method to forecast the number of cumulative confirmed cases in the next days upon the last date of study period. table shows the predicted number and % confidence interval of nationwide cumulative confirmed cases (in thousands). in addition, the point forecasts and the associated % confidence bands for the cumulative confirmed cases in the us from / / to / / are depicted in figure , where we also compare the prediction results with those generated from an arima model. from table , we see that our fts forecasts tends to slightly underestimate the total counts, but the actual count still falls within the prediction intervals. such deviation may be due to the reopening of the schools starting from mid-august, leading to the surge in the cumulative confirmed cases nationwide. when comparing the fts forecasting results with the arima model in figure , we see a narrower prediction interval for the fts results, suggesting that it is preferred than the standard arima model. in this article, we conduct a functional data analysis of the time series data of covid- in the us. based on our results, it is evident that the practice of public health measures (e.g. "stay-at-home" order and mask wearing) helps reduce the growth rate of the epidemic outbreak over the nation. however, the implementation of the business reopening plans seems to have caused the rapid spread of the covid- in some states, e.g. texas and florida. we quantitatively assess the correlation between confirmed and death cases using the fcca. overall, we observe a high canonical correlation between confirmed and death cases, though the figure . average interval scores (scaled by ) for the fts method and the standard arima model for the next days. the fts approach is preferred in that it produces smaller interval scores in most of the cases. note that the rmsfe curve starts from , corresponding to the assumption in section . that the first day of the -day prediction segment coincides with the last day of the study period. canonical variable scores vary from state to state. with the population size in each state carefully adjusted, we see that there is a substantial change in the cluster structure in the early and late times, and / / (the average date of business reopening across the states) appears to be a potential change point. besides, states that are geographically close to the hot spots are likely to be clustered together, and population density (at state level) appears to be a critical factor affecting the cluster structure. in addition, we also propose a forecasting scheme for the nationwide cumulative confirmed cases under the functional time series framework. integrating information from the neighboring data point, the forecasting accuracy from the functional time series approach outperforms that from an arima model. forecasts are also made to the next days of the study period, and comparisons with the actual counts are provided. although our method tends to produce smaller estimated counts for the next days, the actual values still fall within the prediction intervals associated with our forecasts. it is also worthwhile noticing that such underestimation may indicate the effects of school reopening in accelerating the spread of the virus over the country. figure . point forecast and confidence bands for the number of total confirmed cases in the next days (upon the last date of the study period) temporal estimates of case-fatality rate for covid- outbreaks in canada and the united states unsupervised curve clustering using b-splines 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rates: a functional data approach forecasting functional time series rainbow plots, bagplots, and boxplots for functional data coherent mortality forecasting: the product-ratio method with functional time series models funclust: a curves clustering method using functional random variables density approximation functional data clustering: a survey principal component analysis an interactive web-based dashboard to track covid- in real time. the lancet infectious diseases displaying the important features of large collections of similar curves zur spektraltheorie stochastischer prozesse finding groups in data: an introduction to cluster analysis statistics in function space em algorithms for multivariate gaussian mixture models with truncated and censored data canonical correlation analysis when the data are curves uniform convergence rates for nonparametric regression and principal component analysis in functional/longitudinal data selecting the number of principal components in functional data estimating derivatives for samples of sparsely observed functions, with application to online auction dynamics probability theory: foundations, random sequences incubation period of covid- : a rapid systematic review and meta-analysis of observational research finite mixture models a simple, positive semi-definite, heteroskedasticity and autocorrelation consistent covariance matrix the covid- andemic in the us: a clinical update fourier analysis of stationary time series in function space outbreak dynamics of covid- in china and the united states distance-based clustering of sparsely observed stochastic processes with applications to online auctions on flat-top kernel spectral density estimators for homogeneous random fields when the data are functions some tools for functional data analysis applied functional data analysis: methods and case studies fda: functional data analysis a plug-in bandwidth selection procedure for longrun covariance estimation with stationary functional time series an optimal selection of regression variables thinning-based models in the analysis of integer-valued time series: a review a survey of functional principal component analysis forecasting intraday s&p index returns: a functional time series approach bootstrap methods for stationary functional time series intraday forecasts of a volatility index: functional time series methods with dynamic updating epidemiology and clinical features of covid- : a review of current literature who belongs in the family? applications of functional data analysis: a systematic review functional data analysis functional singular component analysis functional data analysis for sparse longitudinal data functional quadratic regression from sparse to dense functional data and beyond meta-analysis of several epidemic characteristics of covid- the authors would like to thank drs. jun yan from the university of connecticut and zifeng zhao from the university of notre dame for valuable comments on the manuscript. key: cord- -pmf stua authors: jourdan, jean‐pierre; bureau, ronan; rochais, christophe; dallemagne, patrick title: drug repositioning: a brief overview date: - - journal: j pharm pharmacol doi: . /jphp. sha: doc_id: cord_uid: pmf stua objectives: drug repositioning, that is, the use of a drug in an indication other than the one for which it was initially marketed, is a growing trend. its origins lie mainly in the attrition experienced in recent years in the field of new drug discovery. key findings: despite some regulatory and economic challenges, drug repositioning offers many advantages, and a number of recent successes have confirmed both its public health benefits and its commercial value. the first examples of successful drug repositioning mainly came about through serendipity like acetylsalicylic acid, thalidomide, sildenafil or dimethylfumarate. conclusion: the history of great‐repositioned drugs has given some solutions to various pathologies. serendipity is not yet useful to find repositioning drugs. drug repositioning is of growing interest. nowadays, a more rational approach to the identification of drug candidates for repositioning is possible, especially using data mining. drug repositioning lies in repurposing an active pharmaceutical ingredient that is already on the market for a new indication. although this strategy has a number of drawbacks and offers certain challenges, it also possesses many advantages, including helping to overcome the attrition currently experienced in the field of new drug discovery. [ ] the history of medicine has been marked by several examples of repositioned drugs, including some very old drugs. most of them came out purely through serendipity. new methods have now been developed, based in particular on data mining, to identify new candidates for drug repositioning. many startups are entirely focused on developing this concept, a journal has been devoted to it (drug repurposing, rescue, and repositioning; ma liebert inc., boston, ma, usa), as well as an annual international conference (the th edition was held in washington dc in ). this article provides a brief overview of repurposing and particularly evokes its most recent scientific basis as well as the new tools, and especially the computational ones, used to render it more efficient. although some historical examples exist, drug repositioning (also referred to as drug repurposing, reprofiling, redirecting, switching, etc.) is a relatively recent concept that appears to have emerged in with an article by ashburn and thor, who provided an initial definition. [ ] they defined drug repositioning as the process of finding new uses for existing drugs, sometimes but not necessarily when they fall into the public domain and become generic drugs. the number of articles devoted to this concept grew exponentially from onwards, [ ] to reach in (based on a search of pubmed on november, th for titles or abstracts containing the terms 'drug repositioning' or 'drug repurposing' and the publication year ). this original definition of drug repositioning has since been extended to include active substances that failed the clinical phase of their development on account of their toxicity or insufficient efficacy, as well as drugs withdrawn from the market because of safety concerns. it should not, however, include substances that have not yet been subjected to clinical investigation. in particular, this rules out substances held in chemical libraries by academic and industry research groups to be screened to identify those with new biological properties, different from the properties for which they were originally designed and synthesised. such compounds usually require hit-to-lead chemistry, in order to optimise the new therapeutic effect sought. similarly, selective optimisation of side activities (sosa), as proposed by professor wermuth, falls outside the scope of repositioning. [ ] in the sosa approach, the biological properties deemed responsible for a drug's adverse effects in a particular indication are isolated and amplified through chemical modification so that the modified drug can be proposed for a new indication. the concept of drug repositioning thus excludes any structural modification of the drug. instead, repositioning makes use in a new indication of either the biological properties for which the drug has already been approved (possibly according to a different formulation, at a new dose or via a new route of administration), or the side properties of a drug that are responsible for its adverse effects. drug repositioning relies on two main scientific bases: ( ) the discovery, through the human genome elucidation, that some diseases share sometimes common biological targets and ( ) the concept of pleiotropic drugs. the description of the elements associated to the complex interplay between diseases, drugs and targets with in silico approaches (data mining, machine learning, ligandbased and structure-based approaches) is one of the key for drug repurposing. [ ] it is now possible to describe diseases by their molecular profile (e.g. the genes, biomarkers, signalling pathways, environmental factors etc. . . involved in their pathogenicity) and to use computational methods, especially data mining, to determine the degree of similarity between diseases that share a number of these molecular features. [ ] for example, parkinson's disease and alzheimer's disease share genes and four signalling pathways [ ] . the existence of protein targets common to several diseases suggests that a given drug might have efficacy against both conditions. most drugs are now phenotypically well characterised in terms of their primary therapeutic effects and their (usually unwanted) side effects. this array of effects results from pleiotropic interactions between the drug and several (primary and secondary) biological targets. a drug can therefore have efficacy against a disease other than the one for which it was initially designed if one of its secondary targets has a role in the new disease. note also that these pleiotropic interactions make it is possible to develop drugs with multiple effects, all intended, that act in synergy to provide greater clinical efficacy, for example, pan-kinase inhibitors used in oncology. like diseases, drugs can be analysed for phenotypic similarity, regardless of their therapeutic indication. if two drugs indicated in different diseases have a high similarity score, they may be effective in both indications. [ ] advantages of drug repositioning drug repositioning has a number of interrelated advantages. they essentially consist of the simplification in the regulatory procedures for introducing a previously approved drug on the market, especially in certain countries such as the united states. this procedure takes into account data previously acquired, in particular on the drug's safety and toxicity, which can make the initial phases of development for a repositioned drug considerably faster, [ ] and therefore cheaper (by over % according to naylor), [ ] and increases the chances of introducing it on the market (by % compared with a novel drug, according to thayer). [ ] one important consideration, however, is that, due to the level of safety required for a drug is highly dependent on its indication, the adverse effects of a drug will be proportionately less acceptable when repositioned for a disease that is less serious or severe than its original indication. [ ] any change in formulation, dosage, or route of administration will require re-examination of the drug's safety profile under these new conditions, in what will be a new medicinal product. the main challenges faced by repositioners lie in the relatively weak intellectual property protection afforded to such medicinal products, which can reduce their return on investment and discourage companies from developing them. [ ] as the drug concerned has already been patented as a new chemical entity, subsequent medicines containing the same entity can only be protected by a new application patent, possibly backed up by a new formulation process. patents on applications are necessarily narrower than those for a new chemical entity in terms of the therapeutic uses they cover. for example, they cannot always prevent generic products containing the same drug being prescribed off-label for the patented application. they are also weaker, in particular in the face of a potential legal challenge on the basis that the new indication was predictable from data in the scientific literature. [ ] the relative weakness of the protection provided by these patents may nevertheless be offset by certain advantages granted to companies repositioning drugs for the treatment of orphan diseases (defined in europe as those with a prevalence no higher than in ), such as fee reductions and a guaranteed period of market exclusivity. [ ] some companies (such as apteeus in france) specialised in 'personalised' drug repositioning, by screening candidate drugs on cells derived from patients with orphan diseases. as mentioned above, the scientific literature abounds with studies aimed at demonstrating the value of an existing drug in another indication, yet the website http://drugrepur posing.info lists only cases in which a repositioned drug made it to the market (accessed on january ). it was estimated in that repositioned drugs generated $ billion in sales worldwide; that is, approximately, one-quarter of the pharmaceutical industry's annual revenue, with five such drugs each generating over $ billion in their new indication. [ ] aspirin the oldest example of drug repositioning is without doubt acetylsalicylic acid (figure ) . initially marketed by bayer in as an analgesic, aspirin was first repositioned in the s, at low doses only, as an antiplatelet aggregation drug. [ ] it is still widely used today in this second indication to prevent cardiovascular events, based on the work of vane, for which he was awarded the nobel prize in medicine in . [ ] previously, dr lawrence craven, a general practitioner at glendale memorial hospital, california, had observed that aspirin, administered for analgesia for his tonsillectomy patients, had the adverse effect of increasing bleeding. aspirin inhibits platelet aggregation by irreversibly inhibiting platelet cyclooxygenase (cox- ), an enzyme responsible for the formation of the prostaglandin precursor of thromboxane a , a potent stimulator of platelet aggregation. aspirin's analgesic and anti-inflammatory effects stem from its inhibition of cyclooxygenase (cox- ), in particular vascular cox- , an enzyme involved in the synthesis of prostaglandins that generate pain and inhibit platelet aggregation. at low doses (< mg/day), aspirin has partial selectivity for cox- and exerts its antiplatelet aggregation effect, which at higher doses is circumvented by concomitant cox- inhibition. aspirin's inhibition of cox- , regardless of the dose administered, is also responsible however for its harmful effects on the gastrointestinal tract, due to this enzyme's role in the synthesis of prostaglandins involved in its cytoprotection. aspirin may soon be repositioned again, this time in oncology. it has been shown that daily administration of aspirin for at least years can prevent the development of many cancers, and in particular colorectal cancer [ ] aspirin's protective effect against cancer is thought to result from cox- inhibition, thus blocking the antiapoptotic effect of cox- in malignant cells and promoting their apoptotic death. [ ] although this second potential repositioning of aspirin offers great promise from a public health point of view, there is little encouragement for it from the pharmaceutical industry, probably due to the intellectual property issues outlined above. it is well known that the world health organization (who) banned thalidomide (figure ) in due to its teratogenicity, which affected thousands of victims worldwide, and continues to affect a second generation, mainly through its use as an antiemetic for pregnant women. despite this, dr jacob sheskin from hadassah university, jerusalem, demonstrated in its dramatic efficacy against erythema nodosum leprosum, an autoimmune complication of leprosy. thalidomide, which achieves this effect by inhibiting the synthesis of the proinflammatory cytokine tumour necrosis factor-alpha (tnf-a), was consequently repositioned by celgene in as an orphan drug for complications of leprosy. [ ] its use must obviously be accompanied by drastic measures to prevent exposure to the drug during pregnancy, including stringent contraceptive measures. this example illustrates how even drugs with an exceptionally poor toxicity profile can be repositioned if the new indication is a rare disease (the estimated incidence of leprosy is cases per year according to http://www.orpha.net, accessed november, th ). like aspirin, thalidomide was repositioned for a second time in the field of oncology. investigation of the mechanism underlying thalidomide's teratogenicity demonstrated its antiangiogenic activity, responsible for the arrested limb development (phocomelia) that occurs after in utero exposure. this activity led to research into its potential use to block or destroy blood vessels supplying malignant tumours, culminating in in its second repositioning as a first-line treatment for multiple myeloma. the same precautions apply, and in europe, the prescribing and dispensing of thalidomide is subject to specific monitoring. sildenafil (figure ) is an example of a pharmaceutical substance that was repurposed before it reached the market. sildenafil was initially investigated by pfizer in as a potential antihypertensive drug. it was shown to produce vasodilation and to inhibit platelet aggregation by inhibiting phosphodiesterase type- (pde ), the enzyme that degrades cgmp. in light of these properties, the focus was shifted onto its potential in the treatment for angina. an unexpected side effect emerged during clinical trials conducted in the united kingdom, in the form of penile erections. this effect is the consequence of vasodilation, by inhibiting pde and consequently blocking cgmp degradation. sildenafil only produces an erection however in the presence of sexual stimulation, leading to the release of nitric oxide (no), which in turn leads to cgmp production. it differs in this way from amyl nitrite, contained for example in 'poppers', which provokes no release and therefore, unlike sildenafil, can be termed an aphrodisiac. this physiological effect led pfizer to market sildenafil in for erectile dysfunction, under the brand name viagra â , generating peak annual sales in this indication in excess of $ billion. [ ] sildenafil was subsequently repositioned for a second time. pfizer continued to study the potentially therapeutic effects of inhibiting pde and proposed exploiting the vasodilation it produces to treat pulmonary arterial hypertension, at one-fifth of the dose used in erectile dysfunction. the idiopathic form of pulmonary hypertension is considered a rare disease ( - million cases per year) and is potentially fatal, which explains why it was relatively easy for pfizer to obtain approval for a second sildenafil product (revatio â ) in in this new indication. [ ] unlike aspirin and thalidomide, which act on different biological targets in the various indications for which they have been approved, and can therefore be described as pleiotropic, sildenafil acts on the same target (pde ) to treat both erectile dysfunction and pulmonary arterial hypertension. dimethyl fumarate (figure ) was first synthesised in . for years, it was only known as a mould inhibitor to protect leather and a cause of allergies, which led to a ban on its use in europe in . nevertheless, dimethyl fumarate has also been marketed as a drug since . it is commonly used in germany to treat psoriasis, under the brand name fumaderm â . having discovered that dimethyl fumarate's anti-inflammatory activity was mediated by increased expression of nrf -dependent antioxidative genes, biogen proposed its use in another autoimmune disease, multiple sclerosis (ms), at higher doses. it was marketed for this indication in , under the brand name tecfidera â . it constituted a major advance in the treatment of ms, because it could be taken orally and is less cardiotoxic and hepatotoxic than the other drugs used in this condition, although it does expose patients to the risk of developing progressive multifocal leukoencephalopathy. in , this product generated almost $ billion in annual revenue. [ ] finally, it should be noted that unlike the previous examples, dimethyl fumarate was not repositioned to make use of a side effect considered undesirable in the treatment of psoriasis, but on the basis of the similarity between the molecular profiles of psoriasis and ms. if there is one field in which attrition in the introduction of new drugs is particularly evident, it is alzheimer's disease, for which no new drugs have been marketed since galantamine in . it is undoubtedly for this reason that so many drug repositioning trials have been and continue to be conducted in this field, albeit unsuccessfully to date. in , over drugs were undergoing clinical trials for this disease. [ ] one-quarter ( ) of these drugs have already been marketed and are therefore being investigated for potential repositioning (table ) . methylthioninium chloride (methylene blue) can also be added to this list, as it has been used to treat malaria and methaemoglobinaemia and is always used as an antiseptic to treat urinary tract infections and non-infectious conjunctivitis. many mechanisms of action that have already been exploited in other therapeutic fields have been reinvestigated in alzheimer's disease for their potential to offer symptomatic treatments (e.g. levetiracetam, cannabinoids, lithium and neuroleptics) or disease-modifying therapies (e.g. insulins, dihydropyridines, nicotine and sartans). the high proportion of existing drugs in the alzheimer's disease pipeline is a good illustration of the fields that rely heavily on the concept of drug repositioning (table ) . the repositioning of drugs for a therapeutic indication other than the one for which they were initially marketed is a growing trend. an illustrative and very recent example of useful repositioning is the study led in marseille which showed that chloroquine and hydroxychloroquine could constitute useful weapons against covid- . [ ] the first examples of repositioned drugs largely came out through serendipity. information technology, and cheminformatics in particular, have now made it possible to facilitate and accelerate the process. data mining is one current method for identifying candidate drugs for repositioning. [ , , ] by defining descriptors from databases for both drugs and diseases, this technology can be used to establish drug-disease pairs and construct models to predict new pairs, which will undoubtedly yield new candidates for repositioning through a more rational process. the main aim of drug repositioning is to combat the attrition and rising costs which, according to 'eroom's law', [ ] are having a dramatic effect on the number of new drugs entering the pharmaceuticals market. however, this approach must be considered as an add-on rather than an alternative to the search for novel drugs. none. all authors participate to this work. all authors revised, added figures, tables and polished it in english. drug repurposing: progress, challenges and recommendations drug repositioning: identifying and developing new uses for existing drugs drug repositioning and repurposing: terminology and definitions in literature selective optimization of side activities: the sosa approach on the 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colorectal cancer by genetic selection thalidomide -a revival story alzheimer's disease drug development pipeline chloroquine and hydroxychloroquine as available weapons to fight covid- drug repositioning for alzheimer's disease based on systematic "omics" data mining a standard database for drug repositioning diagnosing the decline in pharmaceutical r&d efficiency key: cord- -gr zq o authors: ghosh, subhas kumar; ghosh, sachchit; narumanchi, sai shanmukha title: a study on the effectiveness of lock-down measures to control the spread of covid- date: - - journal: nan doi: nan sha: doc_id: cord_uid: gr zq o the ongoing pandemic of coronavirus disease - (covid- ) is caused by severe acute respiratory syndrome coronavirus (sars-cov- ). this pathogenic virus is able to spread asymptotically during its incubation stage through a vulnerable population. given the state of healthcare, policymakers were urged to contain the spread of infection, minimize stress on the health systems and ensure public safety. most effective tool that was at their disposal was to close non-essential business and issue a stay home order. in this paper we consider techniques to measure the effectiveness of stringency measures adopted by governments across the world. analyzing effectiveness of control measures like lock-down allows us to understand whether the decisions made were optimal and resulted in a reduction of burden on the healthcare system. in specific we consider using a synthetic control to construct alternative scenarios and understand what would have been the effect on health if less stringent measures were adopted. we present analysis for the state of new york, united states, italy and the indian capital city delhi and show how lock-down measures has helped and what the counterfactual scenarios would have been in comparison to the current state of affairs. we show that in the state of new york the number of deaths could have been times higher, and in italy, the number of deaths could have been times higher by th of june, . in december , an outbreak occurred in wuhan, china involving a zoonotic coronavirus, similar to the sars coronavirus and mers coronavirus . the virus has been named severe acute respiratory syndrome coronavirus (sars-cov- ), and the disease caused by the virus has been named the coronavirus disease . since then the ongoing pandemic has infected more than million people and has caused more than thousand deaths worldwide. since the initial outbreak, several different studies have tried to estimate the number of infections that stem from a single infected patient in order to predict the potential for transmission of the covid- virus. in most cases, it was seen that r > , implying exponential growth through infection of a vulnerable population. original estimates placed mortality rates for individuals at high risk at . % with those suffering from cardiovascular or kidney disease having even greater susceptibility . the sars-cov- virus has no available treatment as the pathways for proliferation and pathogenesis are still unclear . current treatments are based on those effective on strains of the previous sars coronavirus and mers coronavirus. the sars-cov- virus is able to replicate rapidly during the asymptomatic phase and affect the lungs and respiratory tract, resulting in pneumonia, hypoxia, and acute respiratory distress . infected patients are directly dependent on external ventilation in most cases. with the increasing pressure on the health systems due to reliance on intensive care units or non-invasive ventilation, health strategies were required to be implemented. the concern was to ensure the number of infected patients does not exceed the health system's ability to cope with it. it also focused on increasing the capacities of available health systems at the time. under the conditions at the time, with a highly pathogenic sars-cov- that is able to spread asymptotically during its incubation stage through a vulnerable population, policymakers were urged to contain the spread of the infection, and minimize stress on the health systems and ensure public safety. this was done by issuing orders for widespread lock-down and implementing social distancing measures. all non-essential businesses and services were shut down until further notice. taking measures to reduce stress on the health sector and diminishing the number of infected patients is important to end the pandemic, and understanding the effectiveness of a lock-down enables the distinction of good safety measures from bad ones. analyzing effectiveness of control measures like lock-down allows us to understand whether the decisions made were optimal and resulted in a reduction of burden on the healthcare system, and broke chain of transmission, preventing its spread and reducing the reproductive rate of the virus. any optimal policy considers a trade off between the benefit associated with lock-down and cost of reduced aggregate output. aggregate output decreases as a function of the stringency of the policy, commitment from the government to maintain the level of stringency and adherence of general population. aggregate output decreases through lower supply of labor, lower consumption and hence through lower investment, which results from investors' expectation of a lower marginal product of capital. on the other hand benefit associated with lock-down can be seen through the number of lives potentially saved and in curbing the pandemic early so that economic activity can be restarted early. our objective in this work is to understand the benefits obtained from stringency measures adopted by governments across the world in terms of its health benefits. in the remaining of this section we describe our contribution and related works. subsequently in section we provide a brief overview and mathematical underpinning of the tools that we use and describe our data driven methodology and in section we present our results in three different geographic setup. finally, in section we present some concluding remarks. in this work we consider stringency measures adopted by governments across the world and provide a counterfactual assessment of the benefit from those measures in terms of health benefits. in order to estimate the counterfactual metric (say number of deaths), we use a geographic location as a treatment unit (say italy) and a set of other geographic locations as donor group (say brazil and united states). we take a data driven approach to construct a synthetic control - using pre-intervention period data (say from early february, to march , ) of the donor units and their linear combination, such that the squared error between the estimated synthetic control and the treatment unit is minimized by the choice of weight parameters in this pre-intervention time period. now synthetic control can be extrapolated to estimate the metric. we use multi-dimensional robust synthetic control (m-rsc) as a tool as described in . however, there are few difficulties in applying the tool as it is. firstly, different governments adopted different levels of stringency measures and there were different levels of compliance, and commitment. secondly, there were no 'pure' donor groups as stringency measures were nearly ubiquitous. so we have used various secondary sources of data to score the level of stringency measures , and level of compliance. this allowed us to determine donor groups relative to a choice of treatment unit. finally, we present our results in three different geographic setup -namely in the state of new york, italy and indian city of delhi, and analyze them. in , authors have shown that the reproductive rate of the sars-cov- had significantly decreased after government intervention. they show that the spread of disease was confined if measures were brought into effect early. in , authors use the differential timing of the introduction of stringency measures and changes in google searches for unemployment claims to establish a framework to estimate how each stringency measure contributes to unemployment. authors show that early intervention efforts in the form of non-essential business closure have contributed to less than . percent of unemployment claims. another facet to measure the success of the lock-down is to observe its effects on the health systems. late intervention in the case of italy led to the flooding of hospitals and icus due to exponential spread. however, the national lock-down was effective in reducing the proliferation and decreased the stress on the national health system as observed by authors in . in their paper , authors extend the sir model to include auxiliary state variables in the form of hospital capacity, contact with an infected person, etc. they use a system dynamics model of the outbreak to simulate various lock-down scenarios with recommendations for optimal strategy. in our work we consider the possible outcome if such strategies were not adopted, and present counterfactual scenarios. international travel has also been impacted as a result of efforts to reduce the spread of the coronavirus disease. on the basis of reported cases, models built by show a significant decrease in the number of infections compared to predictions if no travel bans were adopted as an option. their modeling results indicate that travel restriction must be combined with a transmission within the community to curb the spread. in this section we present three examples of the application of m-rsc to derive the counterfactual estimates of possible number of deaths under the changed conditions like delaying or starting the stringency measures at earlier date. we consider three different units of treatments, namely: the state of new york, italy and the indian capital city delhi. in some sense these places have also been termed as regional epicenters of the epidemic. new york has the highest number of confirmed cases in the united states. first case in new york was reported on st march, and new york went into a stricter lock-down on march nd, . we estimate counterfactual considering this as date of intervention. we select among other states from us as donor group using the methods described above. this includes new jersey, california, illinois, and florida among other states. by counterfactual estimate, the number of deaths in new york could have been times higher, and number of confirmed cases could have been times higher. italy was put under lock-down between th march, - th may, . we considered most european countries to model the donor group and selected based on criteria defined above. based on our simulation, we observe that with lock-down measures has been largely successful in italy. without such measures, the number of confirmed case could have been times higher and number of deaths could have been times higher by th of june, . india had one of the most strict stay home order across the country in first phase of the lock-down between march - april ( days), where an entire population of . billion people was put under restricted movement. overall the lock-down had multiple phases, second phase was from th of april to rd of may , and third phase was th of may to th of may, . we present the counterfactual for each of these dates. however, in this case we consider both the daily number of confirmed cases as well as the cumulative number of confirmed cases for phase three of the lock-down. we limit the donor group as all others states of india. figure shows that counterfactual converges closely with the actual at third phase of the lock-down. it should be noted that there are a few discrepancies in reporting. first, there is a weekly seasonality -possibly due to a lesser number of reports over the weekends. second due to a revised higher number of reports on certain dates (high peak). mar, apr, apr linear trend-line fit shows two change points in the growth of number of cases -indicating that the exponential phase came at much later date and growth of the epidemic was under effective control in the earlier stages. since, the stay-home order was applicable across all states and adherence was almost uniform -trajectory of actual and counterfactual remains nearly same. in this work we use multi-dimensional robust synthetic control to understand the effects of stringency measure on covid- pandemic. we construct synthetic version of a location using convex combination of other geographic locations in the donor pool that most closely resembled the treatment unit in terms of pre-intervention period using stringency index and adherence score (using mobility information). results has been compared for the state of new york, italy and delhi, india with actual metric to that of counterfactual predicted by the algorithm. in order to assess the robustness of the predictor we have computed mape and mdape measures and have shown their convergence to less than % absolute error rate. in the future we would like to include additional predictors like testing data, and virus strain information as they become available. another direction of this study is to include parametric epidemic models like sir-f , and compare with m-rsc. as stated above, our objective is to study the effects of government response at an aggregate level in terms of lives saved, and limiting the number of cases that require hospitalization. such interventions can effectively be studied at a comparative level. in other words, if we have data for the evolution of aggregate outcomes, e.g. the number of confirmed cases and deaths, when policy is applied in a group under study versus when the same policy is not applied in a control group. however, government policies were applied at different level across a geographic region. we do not have a mechanism to conduct a randomized trial. hence, we consider using the synthetic control method [ ] [ ] [ ] . in a synthetic control set up, where observational data is available for different groups, we can construct a synthetic or virtual control group by combining measurements from alternatives (or donors). in the following, we provide a brief overview of m-rsc . suppose that observations from n different geographically distinct groups or units are indexed by i ∈ [n] in t time periods (days) indexed by j ∈ [t ]. let k ∈ [k] be the metrics of interest (e.g. number of confirmed cases, number of deceased, number of tests conducted, etc.). by m i jk we denote the ground-truth measurement of interest, and by x i jk , an observation of this measurement with some noise. let ≤ t ≤ t be the time instance in which our group of interest experiences an intervention, namely a government response to control the spread (e.g. stay home order, school or business closure, or mass vaccination). without loss of generality we consider unit i = (say, new york) and metric k = (say, number of deaths) as our unit and metric of interest respectively. our objective now is to estimate the trajectory of metric of interest k = for unit i = if no government response to control the spread had occurred. in order to do that we will use the trajectory associated with the donor units ( ≤ i ≤ n ), and metrics k ∈ [k]. in the following we make two assumptions: ( ) for all ≤ i ≤ n, k ∈ [k] and j ∈ [t ], we have x i jk = m i jk + ε i jk where, ε i jk is the observational noise, and ( ) same model is obeyed by i = in pre-intervention period, i.e. for all j ∈ [t ] and k ∈ [k] we have x jk = m jk + ε jk . as described by authors in , in following we also assume that for unit i = , we only observe the measurement x jk for pre-intervention period, i.e. for all j ∈ [t ] and k ∈ [k]. our objective is to compute a counterfactual sequence of observation m jk for the time period j ∈ [t ], and k ∈ [k], and in specific for t ≤ j ≤ t , and k = , using synthetic version of unit i = . define m = [m i jk ] ∈ r n×t ×k . m is assumed to have a few well behaved properties as required by the algorithm, namely, ( ) m must be approximately low-rank and ( ) every element m i jk shall have boundedness property (for details see ) . to check whether our model assumption holds in practice, we consider n = , t = , k = , with countries as units. we consider number of confirmed cases and number of deceased as two metrics over days between january , and june , . for assumption to hold, data matrix corresponding to number of confirmed cases and number of deceased and their combination should be approximated by a low-rank matrix. as shown in figure , the spectrum of the top singular values (sorted in descending order) for each matrix. the plots clearly support the implications that most of the spectrum is concentrated within the top principal components. the same conclusion holds true when units are states of the united states, and when we consider only countries in the european union. let z ∈ r (n− )×t ×k corresponding to donor units, and x ∈ r ×t ×k correspond to unit under intervention. we obtain m from z after applying a hard singular value thresholding. subsequently, weights are learned using linear regression by computing as described in section , we use m-rsc to construct a synthetic control for the treatment unit using data from multiple control units or donor group using pre-intervention period data. the synthetic control is then used for estimating the counterfactual in the post-intervention period. in our setup, intervention date is typically the date when a stay-home order or lock-down was declared for the treatment unit. however, government policy may have been applied over time with different levels of stringency measures. to understand this we use stringency and policy indices data from oxcgrt , which records the strictness of policies that restrict people's behavior and includes different measures -e.g. school and workplace closure, cancellation of public events, restrictions on gathering size etc. figure , shows the plot of stringency index, with mobility data. it can be observed that the level of lock-down varies over time and geographic region. we use this information in two different ways. first we choose the maximum level of index, first increased level of restriction index, and days after the maximum level of index as various intervention dates and compare their effects. second, we combine this information with mobility data to select the control groups for a treatment unit as discussed below. in order to understand the effect of stringency on a treatment unit for a metric, we need to select a donor group where level of stringency was different or adherence to stringency was different. since, there was a degree of stringency and adherence to such measures at different level -under any possible choice of donor group, we acknowledge, that we will be underestimating the counterfactual -i.e. what would have been without any stringency measures. to estimate the degree of adherence to lock-down measures, we use mobility data from apple, google and facebook. apple mobility data provides a relative volume of directions requests per region, sub-region or city compared to a baseline volume -i.e. percentage change over time from the baseline including weekly seasonality. facebook data provides the relative percentage of population that is staying in the same place and also the percentage of population that moved from a region to another. in facebook data, to quantify how much people move around measure is derived by counting the number of level- bing tiles (which are approximately meters by meters in area at the equator) they are seen in within a day. assuming u d,r is the set of eligible users in region r on day d, and tiles(u) is the number of tiles visited by a given user u in u d,r , total number of tiles visited for that region is given by totaltiles(u d,r ) = ∑ u∈u d,r min(tiles(u), ). change in movement measure is then the difference between a baseline and value on day d for average number of totaltiles(u d,r ). similarly, stay put metric is calculated as the percentage of eligible people who are only observed in a single level- bing tile during the course of a day on an average compared to a baseline. finally, google community mobility report provides a percent change in visits to places like grocery stores and parks within a geographic area from baseline. it can be seen from figure , that the adherence and stringency level do not correspond. for example, in sweden, with increasing level of government measures between march -april, there has not been any significant change in proportion of people staying put or moving between regions. similarly, in other places, it can be observed that while government measures remain at the same level over april, number of people staying put at one place starts declining. selecting donor group: we combine metrics that allow the spread of the virus and similarly combine those that reduces the possibility of spread. we combine them by taking average define a single adherence score. for unit i ∈ [n], ∀ j = i : j ∈ [n], j is a donor unit if adherence score, and stringency index of j is less than i. figure shows this relation in graphical form for a selected set of countries. as per figure , united states, brazil and united kingdom are in the donor group when we compute counterfactual estimate for italy. statistical performance evaluation: in figure we present the distribution of mean and median absolute percentage error statistic for the runs-forecasts from m-rsc algorithm with changing forecast horizon. we consider every mondays between march , to june , , both included to forecast the number of deaths at the end of the day on june , for all states in united states, and compare with actual data. for every state, donor group is selected using the method described above. it can be seen from figure , that both mean and median absolute percentage error statistic are larger, when larger forecast horizon has been considered, and that is to be expected. both mape and mdape converge to a less than percent when horizon is about a week. mape being very large from mdape clearly indicates a right skew in the predicted values. daily update from jhu we use this data to derive metric for units: i.e. number of confirmed cases and number of deceased for each day and geographic locations. facebook movement range maps the relative percentage of population that is staying put and also the percentage of population that moved from a region to another. we use this data in selection of donor units. apple mobility trends relative volume of directions requests per region, sub-region or city compared to a baseline volume, categorized by driving, walking or public transport. we use this data in selection of donor units. oxcgrt strictness of policies that restrict people's behavior, measures combined to provide a score between and , where being most stringent. we use this data in selection of donor units. google community mobility report percent change in visits to places like grocery stores and parks within a geographic area. we use this data in selection of donor units. this exactly corresponds to the places where exponential growth of the pandemic can be observed by march , . the counterfactual prediction for june , on march , for these few places are several times higher as as expected, while, stricter stringency measures were being implemented in the united states around those dates. the reproductive number of covid- is higher compared to sars coronavirus covid- r : magic number or conundrum? estimating excess -year mortality associated with the covid- pandemic according to underlying conditions and age: a population-based cohort study potential treatments for covid- ; a narrative literature review, archives of academic emergency medicine respiratory management in severe acute respiratory syndrome coronavirus infection synthetic control methods for comparative case studies: estimating the effect of california's tobacco control program robust synthetic control mrsc: multi-dimensional robust synthetic control estimating the impact of physical distancing measures in containing covid- : an empirical analysis the impact of shutdown policies on unemployment during a pandemic the effects of containment measures in the italian outbreak of covid- lockdown, one, two, none, or smart. modeling containing covid- infection. a conceptual model the effect of travel restrictions on the spread of the novel coronavirus (covid- ) outbreak variation in government responses to covid- an interactive web-based dashboard to track covid- in real time data for good: new tools to help health researchers track and combat covid- mobility trends reports helping public health officials combat covid- mathematical modeling of infectious disease dynamics we use following five sources of data as described in table all data and code used for this work is made available here: https://github.com/subhaskghosh/lockdown-paper the authors have no competing interests. key: cord- - mfiie authors: aykut, stefan c.; morena, edouard; foyer, jean title: ‘incantatory’ governance: global climate politics’ performative turn and its wider significance for global politics date: - - journal: int polit doi: . /s - - - sha: doc_id: cord_uid: mfiie the paris agreement represents a deep-rooted change in global climate governance. while existing scholarly assessments highlight central institutional features of the paris shift, they tend to overlook its symbolic and discursive dimensions. our analysis shows that the paris architecture combines two core elements: an iterative pledge and review process to stimulate global climate action, and a ‘performative’ narrative aimed at aligning actors’ expectations on the prospect of a low-carbon future. we therefore suggest calling it an incantatory system of governance. we then examine the origins of the new approach and find that the rise of ‘soft law’ approaches and communicative techniques in global climate governance are both indicative of a broader process: the entry of management culture in international organisations. against this backdrop, we examine the prospects, limitations and caveats of the new approach and discuss its wider implications for global politics. the paris agreement adopted in december is widely considered as a major breakthrough in global climate governance, with the potential of becoming a blueprint for other governance arenas (jordan et al. ) . and yet, just years after its adoption, it was already in jeopardy when us president trump announced on june his intention to withdraw from the treaty. the decision completely paralysed negotiations at the un climate summit cop in bonn in november of that same year. interestingly, however, the atmosphere was very different at the 'bonn zone', an area dedicated to non-state and sub-state climate efforts and just a few hundred metres away from the official conference space. a highlight of the 'bonn zone' was the launch of the #wearestillin coalition. under the leadership of billionaire philanthropist, former new york city mayor and un special envoy for climate action michael bloomberg, as well as california governor jerry brown, the coalition brought together american cities, states and businesses committed to fulfilling the us's national emission reduction commitments through bottom-up action. the mood was similarly upbeat at the one planet summit in paris a month later. convened by french president emmanuel macron to mark the cop 's second anniversary, the summit provided business and ngo leaders, representatives from international organisations and national and multilateral development banks, heads of state and government, philanthropists and mayors with an opportunity to both reassert their commitment to the paris agreement and to announce new measures for its implementation. the 'bonn zone' and one planet summit are revealing of the current state of global climate governance. they are symptomatic of more deep-rooted shifts in its organisation, in the levels of engagement, in the actors involved, and the mechanisms through which it operates and produces effects. global climate policy is now understood as a process that transcends the united nations framework convention on climate change (unfccc), and of which transnational initiatives and private governance schemes constitute an integral part (moncel and van asselt ) . furthermore, it is no longer aimed at the production and enforcement of binding reduction targets for states, but builds on a flexible 'pledge and review' system combining voluntary pledges by public and private actors alike, and binding reporting and transparency rules for states (keohane and oppenheimer ) . taken together, these changes have been described as a shift away from a 'regulatory' and towards a 'catalytic and facilitative model' of global governance (hale ) . while such assessments highlight central aspects of the paris shift, they also contain significant blind spots. the bulk of stand-alone articles and special issues on post-paris climate governance focusses on negotiation dynamics and outcomes, the interpretation of the agreement's legal dispositions, or institutional innovations in the post-paris process (jordan et al. ) . in doing so, such analyses tend to overlook an important feature of the new governance regime: its symbolic and discursive dimensions. as illustrated by the examples above, the post-paris process conveys a central role to the emission of 'signals' and the creation of 'momentum' for climate action, through carefully orchestrated global moments such as the one planet summit and climate action summits and highly publicised private initiatives like #werestillin. in other words, in this new governance, performances, symbols and narratives appear to be just as important as the production of rules, institutions and instruments. we therefore suggest calling the new approach an incantatory system of governance. on a general level, the notion of 'incantation' points to the ritualised and repetitive dimensions of global climate governance, with its annual meetings and recurring calls to urgency and action (little ) , as well as to the theatrical dramaturgy of climate summits and their filiation to the 'society of spectacle' (death ) . more specifically, it permits to capture what we believe constitutes a distinctive feature of the new approach: the fact that communicative and symbolic devices are explicitly recognised, by its architects and promoters, as core instruments in the agreement's implementation. a central element in this context is the grand narrative of an ongoing 'planetary transition' to a decarbonised world economy, which is crafted and circulated by key governance actors. by using the notion of incantation, we also wish to engage a discussion on the origins and wider significance of this governance shift. in an increasingly fragmented (biermann et al. ), marketised (newell and privatised (park et al. ) global governance landscape, 'soft law' approaches resting on voluntary commitments (abbott and snidal ) , indicators and best practices (merry ) have been on the rise over the last decades. the paris shift fits within this broader set of transformations, inspired by the adoption of new public management (npm) methods in international organisations. we suggest that these two dynamics-the weakening of legal and regulatory frameworks, and the inflationary use of communicative devices-can be understood as two sides of the same phenomenon: the importation of a business culture in global governance. finally, the notion of incantation points to the need to renew the methods with which we study global climate governance. our aim is not to present the new approach as ineffective per se, but to understand how it plays out in practice, and better appreciate its prospects, risks and caveats. this requires examining the role of rituals, symbols and discourses in global governance, analyse how they produce effects and study how they relate to, or combine with, more traditional governance methods-such as the negotiation of legal documents and the action of international organisations. in line with collaborative event ethnography (campbell et al. ), our analysis is therefore based on repeated collective observations of different spaces of global climate governance, particularly during the paris cop. there, we studied the circulation of people and documents, practices of text production and editing, the role of diplomatic rituals and political performances, as well as civil society mobilisations, scientific events and business happenings . we also analysed how philanthropic foundations and think tanks shaped the 'road to paris' and the discursive context surrounding cop (morena ) . in this paper, we connect the findings of these different lines of research. drawing on discourse analysis (bäckstrand and lövbrand ) , we also reconstruct the narratives circulated by promoters of the new governance approach. that being said, the article's primary goal is to advance a broader conceptual argument. the empirical material serves to shed light on our argument rather than provide a comprehensive, rigorous analysis of one conference or one discourse. the paris approach introduces a series of institutional innovations. it marks a transition from a 'regulatory' approach to global climate governance, with detailed rules and obligations that apply to developed states, to a 'hybrid' system that both combines voluntary submissions and binding review cycles for all states and associates a wider range of stakeholders. however, in the eyes of its architects and main proponents, the new approach does not only rest on new institutions, it also centrally relies on new discursive and symbolic elements. instead of legally binding reduction targets and sanctions for non-compliance, the governance framework laid out in the paris agreement is based on the submission and review of freely determined policy pledges, or nationally determined contributions (ndcs). however, the approach also differs significantly from purely voluntary systems. on the substantive side, it sets two long-term temperature goals: keeping global warming 'well below' °c and 'pursuing efforts' to stay below . °c. the cop decision also sets out the figure of billion usd per year towards developing countries' adaptation and emissions reduction efforts. apart from the . °c target, these figures had already been laid out in the contested copenhagen accord in . accordingly, the paris agreement's main innovations are procedural, rather than substantive (oberthür and bodle ). an 'enhanced transparency framework' is set up to ensure the publicity and comparability of ndcs; a 'global stocktake' is scheduled every years to collectively evaluate the adequacy of national efforts; based on this assessment, countries are expected to 'ratchet up' their pledges in line with the agreement's long-term goals. in sum, the paris framework establishes legally binding obligations of conduct, but no obligations of result (bodansky ) . its implementation has been described as a 'two level game' in which the capacity of domestic civil societies to exert pressure on their governments plays a decisive role (keohane and oppenheimer ) . the paris architecture is therefore understood by its proponents as an iterative process, in which 'the many interdependent parts […] interact in mutually facilitative ways' (hale and roger : ) . the agreement also broadens the scope of stakeholders that participate in global climate governance. in addition to developed countries, developing countries as well as private and subnational actors are encouraged to submit emission reduction pledges. in this respect, paris not only marks a historic break with the north-south divide in global climate politics; it also confirms the rise of 'private authority' and corporate self-regulation in global governance (pattberg ; andonova ) . from centrepiece of a unified and centralised climate regime, the unfccc is now considered as only one of many elements that collectively make up a broad landscape of 'transnational climate governance' (betsill et al. ; bulkeley et al. ). in the lead-up to the paris conference, climate governance scholars reassessed the unfccc's role. they encouraged it to take on an 'orchestrating' function for climate action by states, as well as businesses, cities, regions and federated states (abbott and snidal ; moncel and van asselt ; hale and roger ) . orchestration is thereby defined as an 'indirect mode of governance that relies on soft inducements', as the orchestrator 'works through like-minded intermediaries, catalysing their formation, encouraging and assisting them and steering their activities through support and other incentives' (abbott : ). an oft-cited example is the unfccc's non-state actor zone for climate action (nazca), an online platform launched in 'where actors from around the globe-countries, regions, cities, companies, investors and other organisations-can display their commitments to act on climate change.' to further encourage transnational climate action and link it to the un process, the unfccc also promoted 'high-level champions' for climate action. the 'champions'-usually personalities from the business, political and cultural spheres-put their professional networks and celebrity in the service of climate action. in return, the un arena provides social prestige and symbolic recognition to these individuals. initiatives such as nazca portal or the high-level champions are envisioned as more than mere appendages to national efforts. they are a constitutive 'fourth pillar' of global climate governance alongside mitigation, adaptation and climate finance, intended to 'galvanize' and 'catalyse' global climate action (hale ) . the underlying image is that of a virtuous cycle, in which experiences of past cooperation create trust and confidence among actors and alter their future preferences (bang et al. ) . the concept of 'catalytic cooperation' (hale ) neatly captures this idea. it rests on the claim that global mitigation efforts have wrongly been portrayed as a classic case of a prisoner's dilemma. instead, it is argued that climate action entails first mover benefits for pioneers and increasing returns as the number of followers increases. this may lead to normative change through 'norm cascades' and 'tipping points' that transform the incentive structure and hence the nature of the problem. hence, 'the entire purpose of a catalytic regime' like the paris agreement 'is to shift actors' preferences over time in favour of cooperation' (hale : ) . given the importance of norms, trust and preferences in this governance setup, however, surprisingly little attention have been paid in the literature to global climate governance's symbolic and discursive dimensions. indeed, the defining feature of contemporary climate governance is that signals, narratives and performative moments are at its core. this is explicitly recognised by key proponents of the new approach. laurence tubiana, special envoy of the french presidency to the cop negotiations and one of the architects of the paris agreement, presents the treaty as a 'selffulfilling prophecy', whereby positive narratives 'by producing a convergence of rational anticipations […] contribute as much to change as the agreement itself.' the main objective of post-paris climate governance is no longer the production of new legal norms, but the alignment of state and non-state actors' expectations on the prospect of a low-carbon future. the 'signals' and 'momentum' generated by the governance process underpin the voluntary architecture of the agreement. while the origins of the bottom-up approach in global climate governance are often traced back to the copenhagen climate conference (cop ), fully capturing how and why it came about, and what constitutes its specificities, requires us to go further back in time. indeed, voluntary approaches have been part of the discussions since the beginning of climate talks in the s. we also need to expand our horizons to other areas of global politics, as the approach adopted in paris echoes a wider 'managerial turn' in global politics. prevailing accounts of the paris shift tend to focus on dynamics within the climate regime. and indeed, the idea of a voluntary framework to coordinate the global mitigation effort historically emerged in the run-up to the rio conference. at that time, the eu favoured a 'targets and timetables' approach based on binding reduction commitments for industrialised countries. the us administration criticised the proposal as overtly 'top-down' and 'rigid', arguing that climate governance should involve a more flexible 'bottom-up' approach (bodansky : ) . as a compromise solution, japan suggested in july a pledge and review system combining voluntary country submissions and an international review process to track implementation. however, the targets and timetables approach ultimately won over in kyoto in (damian ) . the voluntary approach resurfaced in the run-up to the copenhagen conference, where countries negotiated on a successor treaty to the kyoto protocol. two years earlier, the so-called 'bali action plan' had introduced the concept of 'nationally appropriate mitigation actions' as a means of getting developing countries to contribute to the mitigation effort. the idea was to encourage emerging economies to make voluntary pledges that would be subject to measurement, reporting and verification (mrv). this, it was hoped, would trigger an incremental process, whereby pledges would progressively be strengthened and ultimately be converted into binding commitments. in the midst of the copenhagen collapse, however, the voluntary approach was ultimately extended to the global north as well. intended nationally determined contributions (indcs) were introduced as a compromise solution between 'nationally appropriate mitigation actions' and the quantified emissions reduction objectives that applied to developed states under the kyoto protocol. the origins of the voluntary approach can therefore be traced back to the early years of the climate regime. there are, however, important differences between the initial proposals and the paris approach. these relate not only to the specific ways in which the paris agreement combines binding and non-binding elements, but also to the broader global setting in which the new climate governance is embedded. this setting differs significantly from the early s. in the post-cold war context of the rio conference, the widely held view was that global governance unfolds mainly through global institution building and the gradual strengthening of international law (levy et al. ; zangl and zürn ) . advocates of pledge and review in the early climate negotiations could therefore frame such a system as a first, incremental step towards more substantial commitments later on (bodansky : ) . this argument appears less plausible today, as the voluntary turn in climate governance coincides with major transformations in global governance. the global diffusion of 'regulatory capitalism' (lévi-faur ) and the rise of 'private authority' (hall and biersteker ; pattberg ) challenge the long-standing supremacy of states and international organisations in global affairs. in a multi-actor world (kaul et al. ) , global governance no longer unfolds through state-led multilateralism alone, but also through forms of 'transnational regulation', 'hybrid governance arrangements' (graz ; andonova ) and networks of corporate self-regulation (müller and cloiseau ; short ) . these transformations had as a corollary the introduction of new governance methods, which originated in the business sector. in the s, new management techniques such as total quality management aimed to provide firms with 'remote control' over their increasingly transnational production chains, through a circular procedural sequence of goal-setting, reporting and auditing (power ) . these techniques inspired a range of national administration reforms during the 'managerial moment' of the s and s (kroeze and keulen ; pollitt and bouckaert ) , before spreading to the global level. corporate social and environmental responsibility (cser) schemes, which rely on a similar circular process of pledging, reporting and review, contributed to this dissemination (zumbansen ; crane et al. ) . through partnerships in such schemes, members of ngos think tanks and international organisations were progressively 'acculturated' to business methods, practices and vocabulary (conley and williams : , ). the spread of cser is also associated with a process of private 're-regulation' (logsdon and wood ; conley and williams ) , whereby businesses became recognised sources of policy proposals at the international level (müller ) . international organisations followed suit over the next decades and increasingly adopted 'soft' and 'experimental' governance methods (sabel and zeitlin ; eckert and börzel ) . the millennium development goals (mdgs), the un global compact and the eu's open method of coordination-three processes launched at the turn of the millennium-constitute paradigmatic examples for this trend. all three combine the definition of common goals, decentralised implementation methods and collective review and benchmarking mechanisms. in addition to coinciding with a broader 'managerial turn', international organisations' adoption of more flexible governance modes also signals their increasing difficulty to develop and enforce binding rules on states (hale et al. ) . hence, the open method of coordination was launched in response to critiques of the eu's overly centralised power structure (regent ; schout et al. ) , while the mdgs came on the back of more than a decade of structural adjustment programmes that spurred growing resistance among developing countries (mcarthur ; shawki ) . the direct consequence of these evolutions is a shift in the normative horizon of global governance. if international relations scholars could still claim in the s that the 'main purpose' of international regimes was 'to harmonize national legislation or to establish rules that can be applied by and to states' (zartman : ) , this no longer pertains to this new type of governance arrangements. from a system organised around the production of legal documents to be transposed into national law, global governance shifted towards a system grounded on the definition of shared goals, voluntary commitments by state and non-state actors, and global review and monitoring processes. while un climate governance was somewhat of a latecomer in adopting the new governance modes, it had been affected by these broader trends well before the copenhagen and paris conferences. since the turn of the millennium, a new 'transnational climate governance landscape' (bulkeley et al. ) progressively took root through the emergence of corporate social responsibility schemes (bulkeley and newell : ) , transnational city networks (betsill and bulkeley ) and corporate carbon trading systems (bernstein et al. ). in the climate diplomacy space, this evolution was closely scrutinised and promoted by a well-experienced and well-connected group of diplomats, ngo, foundation and business representatives, climate policy and communications experts in close contact with the unfccc secretariat and key parties to the convention (morena ) . bringing together individuals with a history of involvement in the international climate diplomacy space-through initiatives like the global call for climate action (gcca) or project catalyst, or informal networks such as the croissant conspiracy or the lionesses -, the international policies and politics initiative (ippi) provides a telling example of how non-state actors strategically mobilised to orientate the international climate debate. participants in the initiative's mid- 'lake tornow' meeting close to berlin include representatives from foundations (ecf, ciff, vasuda), development ngos (oxfam, care international), environmental ngos (greenpeace, wwf), campaign networks (can international, .org, avaaz, gcca), business networks (the climate group), think tanks (e g, wri, ucs, ecofys, track , iddri, germanwatch, grantham lse) and strategic communications (climate nexus) (morena : for participants in ippi, the failure to reach an agreement in was a direct consequence of stakeholders' disregard for wider political and non-state actor dynamics and their influence. experts from the think tank third generation environmentalism (e g, founded in ), for instance, suggested that the copenhagen collapse had shown that 'climate diplomacy has shifted from a relatively narrow focus on the unfccc process, to a more complex and wider discipline that now engages new constituencies and embraces broader geopolitical discussions' (mabey et al. : ) . as johannes meier, ceo of the european climate foundation (ecf, founded in ) explains, experts and activists had failed to recognise that change happens 'in rather oblique and non-linear ways' and that there is a 'need to pay more attention to politics and even to the polity' (meier ) . in its strategy document, ecf further argues that 'the radical policy change that will be required' entails moving not only policy-makers, but 'society as a whole, from the progressive to the conservative, right to left, engaged and disinterested' (european climate foundation : ). the new priority in the lead-up to paris was therefore to stimulate actions at multiple levels and locations, both within and beyond the unfccc, and involve a wide range of stakeholders, to create the conditions for a new type of global climate agreement. the idea was to deliver an agreement that combined a long-term goal that sends 'a clear signal to policy makers, businesses, investors and the public that the low-carbon climate-resilient economy is inevitable' (morgan et al. : ) , with 'bottom-up' commitments that are regularly updated and subject to robust transparency and accountability provisions. this, it was suggested, would enable climate diplomacy to use the 'groundswell' of 'nonstate action' to 'reinvigorate' global climate governance (chan et al. ) . through these and similar proposals in the run-up to paris, climate policy experts and representatives from think tanks, philanthropic foundations and environmental ngos successfully positioned the pledge and review approach as a credible and pragmatic alternative to the legally binding, top-down system that had prevailed up to copenhagen. critical governance scholars and ethnographers of global institutions have long argued that discourses, narratives and symbols constitute key elements in the making of global orders and pointed to the importance of rituals and performances in global mega-events like un climate summits. and indeed, beyond the -page treaty and accompanying -page cop decision, the paris cop also gave birth to the mobilising narrative of an ongoing 'planetary transition' to a low-carbon economy. the making of this narrative can be traced back to the aftermath of cop in copenhagen, when the production and dissemination of discursive frames became a central concern for climate governance actors. in the process, communication practices became a key strategic tool for the architects of the paris approach. making sense of the contemporary transformations of global climate governance requires an analytical vocabulary that adequately captures its discursive and symbolic dimensions. this points to at least two existing lines of research. first, research on discourses and norms highlights the constitutive power of language, knowledge and ideas in global environmental governance (bernstein ; oels ; pettenger ; hughes and paterson ) . lövbrand ( , ) , for instance, show how three broad discursive formations-'ecological modernization', 'green governmentality' and 'civic environmentalism'-distinctly shaped global climate politics in the post-kyoto and post-copenhagen eras. global climate discourses also extend beyond the realm of un climate diplomacy. they have disciplining effects on the everyday and participate in the creation of subjectivities (paterson and stripple ) . they provide 'discursive hooks' to actors seeking entry into the climate arena (allan ) and enable strategies of 'climate bandwagoning' (jinnah ) . moreover, their circulation contributes to a 'climatisation of global debates', whereby issues formerly unrelated to climate policy are increasingly scrutinised through a 'climatic lens' oels ) . un summits, which attract new actors and issues into the climate arena, play an important role in this progressive extension of the thematic scope and symbolic reach of climate governance. this resonates with a second line of research which focuses on the symbolic and performative dimensions of global environmental summits (blühdorn ; campbell et al. ) . ethnographer paul little ( ) provides a fascinating account of the role of performances and rituals at the rio conference. analysing the endless litany of speeches by heads of state and government during the opening ceremony, he shows how these conveyed to the respective home audiences the idea that 'world leaders' were best suited to address global problems. death ( ) makes a similar argument in a foucauldian study of 'theatrical techniques' at the he argues, has come to constitute a 'distinct technology of government'. despite being unsuccessful in terms of negotiations, the two summits constituted attempts 'to inspire and conduct the self-optimisation of the watching global audience'. for these authors, global mega-conferences cannot be reduced to formal negotiation outcomes; they are also important loci for the production of meaning, through the emission of signals, frames and narratives. such perspectives permit to shed new light on the discursive context of the pre-paris process. indeed, copenhagen also marks the start of a new 'positive' narrative around climate change, which would come to form a core feature of the new climate governance. for the group of stakeholders mentioned above, copenhagen had not only been a diplomatic fiasco, but also a failure in terms of communication. it had effectively failed to shape the overall narrative on climate change in a positive way (morena : , ) . too little attention had been paid to the symbolic and discursive dimensions of climate diplomacy. to succeed, the paris conference therefore had to send 'unambiguous signals that the world will shift its economic and social activity toward more climate-friendly and sustainable pathways' (oberthür et al. : ) . to do this, a range of individuals were mobilised and tools were created to ensure that stakeholders in the climate debate sent the right message to the right audience at the right time (morena ) . communications efforts were orchestrated by discreet 'unbranded' initiatives such as the global strategic communications council (gscc) or climate briefing service (cbs) whose communications experts '[coordinated stakeholder] voices at the national and international levels to help shape the national offers as they are being drafted and the thinking around the international agreement'. they focused their communications efforts on global and national climate-relevant 'moments' leading-up to the paris conference; from g and g summits, to the rio + conference ( ) and associated green growth/green economy agenda, to china's adoption of its new -year plan, to the launching of climate-related reports (ipcc reports, new climate economy report, unep emissions gap reports…). these communications efforts mobilised a wide range of stakeholders, from climate 'outsiders' active on the margins of the official negotiation process to climate 'insiders' working closely with parties to draft a new treaty (de moor et al. ; newell ) . christiana figueres, unfccc executive secretary at the time, played a key role in these efforts. she provides a fascinating account of her intense lobbying work for a climate agreement in a recent nature commentary. her primary task, she contends, consisted in spreading optimism: i immediately realized that, before we could consider the political, technical and legal parameters of an eventual agreement, i had to dedicate myself to changing the mood: there could be no victory without optimism. i decided to set a clear intention: even if we did not know precisely how, a global deal would emerge, simply because it was necessary. it was that contagious frame of mind that led to effective decision-making, despite the enormous complexities under which we were operating. when the paris agreement was achieved, the optimism that people felt about the future was palpable -but, in fact, optimism had been the primary input. (figueres ) among the groups that actively promoted a new climate narrative were also progressive business interests like the we mean business coalition launched at the nyc climate week (benabou et al. ) . in its first report the climate has changed, the coalition argues that 'the transition to a low-carbon economy is already happening' (we mean business : xiv) and attempts to demonstrate that 'ambitious climate action makes business sense' (ibid.: viii). the transition is depicted as a dynamic, polycentric process where 'bold business action' and ambitious policy-making are mutually reinforcing (ibid.: vii). a follow-up publication shaping a catalytic paris agreement contains a detailed proposal for a new climate treaty (we mean business ) . according to the authors, such an agreement should combine voluntary and binding elements to '[create] an inclusive enabling environment for all stakeholders-including business' and fix an ambitious temperature target to 'send a political signal that long-term decarbonisation is inevitable' (ibid.: ). in other words, its purpose would be largely symbolic. by further substantiating the narrative of an ongoing and unavoidable low-carbon transition, the successful adoption of an 'ambitious' agreement would encourage low-carbon efforts by businesses, investors and citizens. this would in turn generate momentum for more ambitious national policies, thereby setting in motion a self-reinforcing process towards decarbonisation. as former us secretary of state john kerry explains in the rolling stone: if nations are taking it seriously and setting targets, even if they don't make them, that will generate massive investment and a huge amount of private-sector activity […] and then you have to hope that somebody comes up with clean-energy technology, which makes it competitive with fossil fuel, and then, boom, you get your low-carbon economy. in the lead-up, during and on the back of cop , the agreement's core architects set up an elaborate communications campaign whose purpose was to shape a new climate narrative centred on three elements: the low-carbon transition is already underway; it presents unprecedented economic opportunities, and its successful implementation rests on the cooperation of actors from all sections of society. this, it was believed, would generate 'momentum' around the 'paris moment', and more generally the benefits of decisive climate action. for the architects of the paris approach, narratives and signals were not only key to achieving a positive outcome at cop ; they are equally important in the implementation of the paris agreement. for laurence tubiana, the post-paris process '[is] all about momentum.' christiana figueres ( ) urges all stakeholders 'to move firmly into a state of stubborn optimism' and to 'conceive of success and take immediate steps towards it'. following the adoption of the paris agreement and its subsequent ratification and entry into force, a priority for its main proponents was therefore to keep the 'paris prophecy' alive in the hope that this would lead stakeholders to ramp up their levels of ambition in the lead-up to the next global stocktake in . forging the right narrative and controlling the discursive context of global climate governance thereby become key concerns. in the final chapter, 'a new story' from their book, the future we choose, c. figueres and tom rivett-carnac describe this task as follows: right now, the predominant stories we are telling ourselves about the climate crisis are not very inspiring. but a new story can reinvigorate our efforts. when the story changes, everything changes (figueres and rivett-carnac : ) . the purpose of climate summits changes accordingly. in the post-paris period, negotiations increasingly lose their pivotal role. instead of focusing on the arduous and conflict-ridden process of political bargaining, rituals and performances occupy centre stage. 'the ideal cop would send a positive signal(s) to the international community, including investors, regarding the parties' and other stakeholders' direction of travel' writes susan biniaz ( : ) , lead climate lawyer for the u.s. state department from to and another key actor in paris. in a growing number of high-level and highly mediatised climate action summits, the unfccc now takes on the role of 'travelling salesman' for ambitious climate action. cops or climate action summits are essentially about communicating on the urgency of the climate crisis, highlighting the economic and social benefits of climate action and showcasing existing efforts-especially corporate climate action-to address the crisis (aykut et al. ) . hence, while rituals, discourses, theatrical techniques and political performances have always played an important role in global politics more generally, the post-paris climate governance stands out. whereas in other governance arenas their role tends to be understated or played down, in the climate arena, communicative and symbolic elements are explicitly recognised as core instruments in the implementation of the paris agreement. we suggest the term 'incantatory governance' to characterise this new approach. in so doing, we aim to highlight both the iterative, cyclical process created by the paris agreement's review mechanism and the central role of performative narratives and signals in the post-paris setup. as pointed out earlier, our intention is not to dismiss the approach as 'merely' symbolic and therefore ineffective. ethnographic research shows that incantatory rituals can produce real-world effects and fulfil important social functions. claude lévi-strauss, for instance, famously investigated the 'pragmatic effectiveness of symbols' in shamanistic cure (muniesa : ) . the repetitive utterance of words and mobilisation of symbols, he writes, 'provoke[s] an experience', which can produce therapeutic effects (lévi-strauss : ) . an increasing body of research shows that modern institutions also heavily rely on symbols, rituals and narratives: storytelling and drama constitute key features of contemporary management culture (czarniawska ) , while 'fictional expectations' shape the functioning of capitalist systems (beckert ) . accordingly, death ( : - ) criticises what he terms the 'anti-theatrical prejudice' in social science scholarship. 'symbolic aspects of summitry are not sideshops', he contends, 'but essential to the manner in which summits govern the conduct of global politics'. instead of opposing 'symbolic' politics to a hypothetical 'real' politics, we should accept that symbols and narratives form part and parcel of contemporary liberal governmentality (blühdorn ; death ) . the imminent conclusion of the regime building process therefore represents a critical juncture not only for un climate governance, but also for social science research. what are the prospects, risks and caveats of the new approach? as the focus shifts from negotiation to implementation, a new chapter opens for the unfccc and its annual cops. while a thorough assessment of the effectiveness of the new governance approach would be premature, developments since the paris cop point towards two main issues with the new approach. president donald trump's decision in june to withdraw from the paris agreement represented a severe test for the post-paris process. given the historical responsibility and political weight of the usa, the decision weakened the unfccc as the central forum of global climate governance. by sending a very negative signal, the us administration's retreat also threatened to undermine the 'paris prophecy', which, as we have shown, forms a crucial part of the post-paris climate governance framework. to uphold the momentum, it therefore became essential to show that the international community-state and non-state actors alike-was still committed to the goals laid out in the paris agreement, with or without us federal support. in response to trump's decision, the international climate community coordinated a series of high-profile initiatives. notable examples include the #wearestil-lin and america's pledge initiatives. in both cases, the idea was to reaffirm the fact that despite trump's decision, the usa, through the combined efforts of business leaders, university chancellors, mayors and state governors, would fulfil-and even surpass-its paris commitments. in addition to mobilising non-state and sub-state actors, the priority was also to find a new 'climate champion' and saviour of multilateralism to fill in the gap created by the us exit. despite his status as relative newcomer to the climate cause, french president emmanuel macron was rapidly elevated to the rank of 'champion of the earth'. the organisation of a press conference at the elysée palace the day after trump's announcement in june and the hosting of the one planet summit in december were coordinated efforts to retain control of the overall climate narrative and through this, keep the 'paris prophecy' alive. in our view, these and other concerted efforts to 'save' the paris agreement and 'ramp up ambition', by being almost exclusively centred on the production of narratives and signals, pose the risk of further 'virtualising' global climate governance (carrier and west ). moreover, the paris approach's 'performative' dimension complicates the task of publicly recognising that targets-such as the . °c target-are out of reach (geden a) . faced with the need to uphold a positive storyline, stakeholders of global climate governance are incentivised to 'move the goal posts' through 'creative accounting' or unproven techno-fixes, as exemplified by the massive amounts of 'negative emission technologies' included in global decarbonisation scenarios (anderson ; geden b) . by doing so, they risk delaying the necessary acknowledgement that current modes of development are inherently unsustainable. in other words, there is a real danger of deepening the rift between an 'international community' seemingly committed to ambitious climate action and the reality of 'business as usual' in a rapidly warming world. this discrepancy is not unique to the current period. the last decades saw a growing disconnect, or 'schism' (aykut and dahan ; aykut ) , between, on the one hand, a slow and procedural un arena focused on negotiating carbon emission reductions, and on the other hand, a staggering acceleration of a series of phenomena that are at the heart of the climate crisis but outside of climate governance's remit. chief among these are the dynamics of economic and financial globalisation, the expansion of extractivist development models and the global spread of western consumerist lifestyles. indeed, 'climate policy' is an inherently crosscutting policy domain. it touches on a range of very different issues, from development and energy policy, to trade and financial regulation, as well as agriculture and urban planning. yet, the governance of these issues follows very different logics. the voluntary and soft-law approach to climate governance contrasts with the situation in other issue areas. some of these are regulated through 'hard law', enforced by international organisations, while others are exempt from global regulation, and governed instead through global market dynamics and power relations (kingsbury ) . each governance arrangement draws on specific tools and mechanisms to exert influence on relevant actors and practices. the shift in global climate governance brought about through the paris agreement has exacerbated these differences. indeed, while it is very ambitious in terms of its global temperature targets, the paris agreement is evasive when it comes to spelling out the changes that will be required to attain them. there is no mention, for instance, of phasing out fossil fuels or 'decarbonising' the global economy, nor, for that matter, of encouraging renewables or energy efficiency. another important issue that is completely absent from the text is international trade regulation (brandi et al. ) . this links back to the 'fragmentation' of global governance, whereby the management of a problem falls upon diverse international organisations with potentially contradictory objectives (biermann et al. ). these fragmentations owe nothing to chance but are rather the product of structural 'selectivities' that are rooted in the global order and protected by powerful interests (brunnengräber ) . saudi arabia and other fossil fuel interests, for instance, actively worked to prevent any discussion on energy questions within the climate convention, so as to thwart any international regulation in that domain (aykut and castro ; depledge ) . the same applies to trade, whose absence from the climate negotiations is due to the active efforts of a coalition of industrialised and emerging economies (luterbacher and norrlöf ) . it is worth noting, however, that the similarities between the two cases stop there. unlike energy, international trade is regulated through a fairly robust international organisation, the world trade organisation (wto) and a number of legally binding bilateral treaties (mattli and woods ). from 'non-governed' issues where the strongest get their way (such as energy), to issues that are regulated through legally binding treaties (such as trade), to those managed through soft law (such as human rights and most environmental issues), we are in the midst of an increasingly complex global governance landscape. this landscape is not set in stone but is the product of political strategies and historical struggles that continue to act as barriers to an effective management of the climate crisis. the multi-dimensional nature of the problem calls for an in-depth rethinking of the established global order, beginning with the existing division of labour and hierarchy between international organisations, and the regulatory void when it comes to strategic domains such as fossil fuel production and trade. scholars of international relations generally agree that a central feature of international regimes is that actors' expectations converge in a given area of international relations (krasner ) . while it has generally been thought that such convergence is best reached through binding regulations and the building of strong international organisations, this no longer holds for paris-type governance arrangements. a growing body of scholarship therefore examines the paris shift and considers its consequences. in this article, we argued for the need to broaden the perspective adopted in this literature along two broad lines. we first suggested to re-embed the voluntary turn in climate governance within broader transformations in the ways that global problems are governed. in the course of these transformations, neo-managerial tools and techniques are increasingly adopted by international organisations. second, we argued that the new climate governance is not only characterised by institutional innovations. it also builds on narratives and signals as central means of implementation, by aligning actors' expectations and coordinating their behaviour towards a low-carbon future. based on these observations, we suggest the term incantatory governance to characterise the paris framework. the term highlights the iterative nature of the new 'bottom-up' and voluntary governance process. it also points to the increasing prominence of communicative devices and marketing techniques in global climate governance. our analysis suggests that both of these evolutionsthe rise of 'soft law' approaches and the widespread deployment of communicative techniques-reflect a much broader process: the entry of management culture, techniques and actors into global environmental governance. having said this, we consider the analyses laid out in this article as no more than a starting point. we hope that they will inspire further research on the discursive and performative dimensions of the new climate governance, but also beyond. indeed, given the climate arena's central position in global politics, one can expect other governance spaces to draw inspiration from it. this makes it all the more important to scrutinise the mechanisms of post-paris climate governance, evaluate their effectiveness, signal potential drawbacks and understand the governance shift's wider implications. one final observation should be made relating to the challenges facing those who express more fundamental reservations about the brave new world of 'performative' or, as we have termed it, 'incantatory' governance. critical perspectives are important in order to both problematise the selective and fractioned geographies of global regulation and highlight the shortcomings of a climate governance architecture that brushes aside issues that are key to solving the problem. and yet, there is little room for radical or fundamental critique under the current climate governance since such critique risks undermining the 'paris prophecy' by sending negative 'signals'. how then can we avoid both complacent self-censorship and a sterile, and potentially destructive, critical stance? we can perhaps begin by recognising that in a fractured and divided world, and in the face of multiple and interrelated crises, the paris agreement provides a snapshot of what can presently be expected from the un system and the unfccc process. it therefore goes without saying that the climate problem cannot be solved within the un system alone and that the paris agreement only forms one piece of a much larger puzzle. solving this puzzle will require actions at multiple levels and in a wide range of arenas. while this includes businesses, it also encompasses states and regulations, other international organisations, as well as collective mobilisations and social movements, which appear as key to shifting current power relations in favour of transformative change. it will also involve long and arduous efforts to re-politicise the climate debate and show the connections between climate change and other important issues that have traditionally been ignored in, or excluded from global climate governance. with their own rituals, heroes and discourses, recent and innovative climate protests, from 'fridays for future' to extinction rebellion, can be interpreted as attempts to do just that. our concluding remark is inspired by the current situation of global confinement and lockdown in the struggle against the covid- virus. in many countries, and especially of the global north, the measures imposed by governments to address this global health crisis are unprecedented since world war ii. the command-and-control approach combining quarantines, curfews and emergency laws stands at the antipodes of the managerial and 'incantatory' governance approach that we just analysed. it is too soon to say how this crisis and its political and economic consequences will affect the prospects of global decarbonisation. however, the contrast between these two governance models-one centred on transnational coordination through signals and narratives, the other on commandand-control and the sovereign power of nation-states-is striking. it could well be, therefore, that the covid- experience deeply affects and transforms, yet again, 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makes good business sense the business brief. shaping a catalytic paris agreement make law, not war: internationale und transnationale verrechtlichung als baustein für global governance two's company and more's a crowd. the complexities of multilateral negotiation the conundrum of corporate social responsibility: reflections on the changing nature of firms and states key: cord- -y wwy authors: white, anthony r. title: the pharmaceutical company approach to antibiotic policies date: journal: antibiotic policies doi: . / - - - _ sha: doc_id: cord_uid: y wwy nan the word "policy" is defined as "prudent conduct, sagacity; course or general plan of action (to be) adopted by government, party or person." in this sense, antibiotic policies range from local hospital or community policies to national treatment guidelines for specific infections, regulatory policy, and regional and global strategies. all have the potential to impact on the pharmaceutical industries' (pharma) integrated activities of discovering, developing, and marketing antibacterials. this article reviews the relationship between antibacterial policies and the role of pharma. for almost years, pharma has played a major role in discovering, developing, and making available antibacterials for human and veterinary use (garrod et al., ) . today, more than in recent decades, there are high demands on pharma to deliver to patients new, effective antibacterials to replace those agents for which clinical utility is compromised by emerging bacterial resistance. this "crisis," with the daunting prospect that one of the most beneficial discoveries and developments in the history of mankind could become extinct within a mere few human generations, has understandably also prompted a wide range of recommendations, guidelines, and policies with the intent of preserving and protracting the utility of our current antibacterial armamentarium. however, in some cases, these policies themselves are reducing the chance of success of pharma delivering the antibacterial agents for the future. in order to succeed, pharma will need to adapt to the new environment, but there is a very real and immediate danger that the extent of change in the environment is presenting significant hurdles that will prevent or delay the discovery and delivery of new agents. a greater understanding of the collective impact of policies on pharma's ability and willingness to conduct sustainable research and development (r&d) of antibacterials is needed along with a cooperative partnership approach. there is a need for governments, nongovernmental organizations (ngos), policy-makers, regulators, and infectious disease experts to collaborate with pharma to establish ways to maximize the chance of bringing new antibacterials into clinical use and sustain their utility. unfortunately, individual pharma companies continue to exit from antibacterial discovery and development and the pool of major companies is likely to soon be occupied by a handful or less, severely restricting the ability of pharma to meet the medical needs of infectious diseases, particularly those which require flexibility and responsiveness, such as epidemics and those arising from bioterrorism. once r&d efforts are terminated it will require substantial new investment, both in monetary and intellectual terms, as well as time to re-initiate effective programmes. without continued, sustainable, and successful antibacterial r&d, we will certainly be facing the prospect of "antibacterial extinction." there is no doubt that research-based pharma has for many years been instrumental in providing the wide range of clinically important agents which are available today. garrod et al. ( ) described three eras of antimicrobial chemotherapy: • alkaloids: from and use of cinchona bark to treat malaria • synthetic compounds: from and the discovery of the arsenical salvarsan by ehrlich, and including prontosil/sulfonamides in • antibiotics: from with the discovery of penicillin. pharma has been predominant in discovering or developing antibacterials in the two most recent of these three eras. while not all antibacterials were discovered by pharma, many of the early members of today's antibacterial classes were brought to clinical use through the development and scale-up activities of pharma, in some cases through collaboration by a number of companies, notably in the development of penicillin g in the s. the majority of discoveries and developments that have produced the major classes of antibacterials, as well as the many significant developments within these classes, have been the result of the pharma industries' innovation and expertise. it is probable that without the efforts of research-based pharma and the associated integrated competitive and commercial aspects, many of today's agents would not yet have been discovered, developed, or available to physicians. the now somewhat famous declaration in by the us surgeon general, william stewart, testifying before us congress that it was time to, "close the book on infectious diseases," illustrates the degree of success that was perceived to have been achieved at that time. although there is a sector of the pharma industry that focuses on the sale of generic versions of agents discovered and developed by the research-based companies, these activities mainly require only manufacturing and distribution expertise. now, as in the past, it is the research-based companies to which we need to continue to look to for the provision of agents for the future. the discovery, development, and appropriate use of new agents is a key theme in the major antibacterial strategies and policies to combat resistance which have been reviewed by carbon et al. ( ) . against this background it may be considered surprising or even alarming that the interscience conference on antimicrobial agents and chemotherapy for (icaac, ) includes a symposium entitled why is big pharma getting out of anti-infective drug discovery? a review of abstracts on new antibacterial agents or targets/methods presented at icaac indicates some companies involved in this field including of the "top " companies as determined by sales (table ) . of the total, companies presented data from established classes (␤-lactams/ inhibitors, lipopeptides/glycopeptides, fluoroquinolones, oxazolidines, protein synthesis inhibitors) and of these companies were from the top companies by sales. twenty-one companies presented data on targets or methods, thirteen exclusively, and seven on novel agents or immunomodulators (table ) . this analysis represents only a snapshot of those companies presenting at icaac and not the total discovery programmes currently being undertaken, some on areas not yet disclosed, others since terminated. despite the wide range of presentations by pharma at icaac , there has undoubtedly been a consolidation in antibacterial r&d in the large pharma companies, and a dearth of novel agents emerging from the pipelines. increasing discovery activity in smaller companies may offset this, although the capabilities of smaller companies to develop antibacterials to market may be limited in the face of increasing development hurdles. the future model of discovery and development may well have to rely on collaborations and cooperations between small/discovery and large development/supply pharma. mergers and acquisitions have resulted in the key players becoming significantly fewer and each withdrawal from antibacterial development has an anthony r. white have evolved from some to companies with antibacterial r&d heritages. some are the result of none or few amalgamations while others are many-fold. of the top companies, less than half are believed to be currently active in antibacterial r&d. within the remaining companies the discovery effort has been directed towards either defined niche disease areas, or large "blockbuster" commercial areas, with a consequent reduction in diversity across the industry. individual specializations within pharma, such as was the case when companies almost exclusively worked on penicillins (beecham research laboratories), cephalosporins (glaxo), or quinolones (bayer ag), for example, are becoming less as the companies look to satisfy commercially attractive target product profiles from whichever molecular classes that are available through their r&d efforts or in-licensing. the emphasis on development of line extensions of existing molecules has also increased as a means to improve patient benefits such as convenience and efficacy and importantly for pharma, to maintain development and commercial activity to offset patent loss and bridge the gap to the introduction of new agents. critically, of the companies which have exited or severely reduced their antibacterial r&d (e.g., aventis, bristol-myers squibb, eli lilly & co, roche-chugai, and wyeth research) (idsa, ) , these decisions have been taken relatively recently at a time when the need for new effective antibacterials is arguably greater, but also at a time when policies and regulations for the development and use of antibacterials have proliferated. the crucial issue will be the ability of companies, big or small, alone or in collaboration, to bring novel agents to the market and whether the agents being discovered and developed today will satisfy both the medical and the commercial needs to provide a sustainable future for antibacterial chemotherapy. continued investment and commitment of big or small pharma into research for new antibacterials to meet current and future clinical needs is crucial and yet is at a crisis and being impacted by antibacterial policies which are increasingly being developed and implemented. the infectious disease society of america (idsa) newsletter, march , entitled the future of antimicrobial drug availability: an impending crisis (idsa, ) , highlights the current issues facing the development of antimicrobial drugs. infectious diseases are the second leading cause of death and the leading cause of disability-adjusted life years worldwide. antibacterials are key tools in treating many globally important infectious diseases, including meningitis, pneumonia, diarrhoeal illness, skin and bone infections, tuberculosis, sexually transmitted infections (gonorrhoea, syphilis, and chlamydia), hiv/aids-related bacterial infection, and diseases that may be spread as a result of bioterrorist acts. withdrawal from antibacterial research will have a major impact on global health. a letter to the journal of the american society for microbiology (appelbaum, ) states that, "a crisis has developed and we are doing nothing about it," highlighting that pharma companies are reducing or closing their antibacterial research and that pipelines are, "practically empty." appelbaum suggests that, unlike drugs for long-term treatments, there is a lack of funding for research into antibacterials, one of the reasons for this being the overly stringent approval criteria imposed by the federal drug agency (fda), making it practically impossible or prohibitively expensive to bring new antibacterials to market (appelbaum, ) . for those who have worked in the antibacterial field from the hey-day of discoveries in the s and s it is very apparent that the number of new chemical agents being progressed to man and subsequently marketed is much reduced. idsa reported that of new medicines reaching the us market in none was an antibacterial, with only new antibacterials being approved since (idsa, ) . a review of company reports for the major pharma companies listed only new antibacterials in the drug pipeline out of agents listed ( . %) (idsa, ) and that on average the time to develop new antibacterials was - years from discovery to first approval. although pharma has continued to explore ways to increase efficiencies and decrease development times, these have largely remained stable due to the increased numbers of patients required for new drug applications (ndas), as well as increased complexity and costs in meeting regulatory approval requirements (kaitin and dimasi, ) . an important consideration for pharma companies involved in r&d and commercialization of therapies for a range of disease areas, is that other therapeutic areas are increasingly more profitable than antibacterials. today, there are fewer large companies specializing in antibacterials as a main r&d area. investment decisions are made across and between therapeutic areas and pharma has an obligation to maintain shareholder value and commercial viability or else no new drugs would become available in any therapy area. the reasons for the "crisis" in antibacterial r&d, manifested by fewer new agents or classes reaching clinical use, are complex and multifactorial but undoubtedly the impact of the changing environment of regulations, guidelines, and policies on the development and use of antibacterials is an important contributory factor. stated simply, antibacterials are developed and used to overcome bacterial infection. the progressive discovery and introduction of new classes and agents extended the range of bacteria and associated infections that could be successfully treated. antibacterial resistance, which has emerged from the beginning of antibacterial chemotherapy, has provided a key medical reason for the development of new agents, along with the wish to improve efficacy, safety and tolerability, and dosing convenience. anti-infectives are unique (with the exception of some increasing evidence in oncology) in that the target of their action can change and provide the rationale, medical need, and commercial incentive for the development of new agents. the need for new agents or classes to combat antibacterial resistance is arguably greater today than it has been for some decades. concerns about emerging resistance, increasing loss of utility of existing antibacterials and associated negative impacts on health have given rise to a wide range of strategies (strategic plans, action plans), policies (rules and directives), and guidelines or guidance. some are advisory and others mandatory but all constitute broad policy with respect to the development and use of antibacterials. the sources of policy activities range from global ngos, such as the world health organization (who), regionally based bodies such as the european union (eu) and european medicines evaluation agency (emea), countrybased public health and regulatory bodies such as the centres for disease control (cdc), and fda, and physician associations (idsa), to the local, and institutional level within countries. a comprehensive summary of the more influential recommendations for the control of antimicrobial resistance has been prepared by carbon et al. ( ) (toronto declaration, ) , and one from the who global strategy for containment of antimicrobial resistance ( ). all these recommendations date from to with the majority being published between and . undoubtedly, there are more or updated recommendations in the pipeline and continuing activities of bodies addressing the topic, such as the usa cdc task force (idsa, ; shlaes and ryan, ) . common themes, which emerge from the range of recommendations related to antibacterials and antibacterial resistance, are the need for: • surveillance of resistance and antibacterial usage • optimizing antibiotic use (reduce inappropriate use), guidelines, and policies • education of professionals and patients into judicious/prudent use • prevention through infection control, interventions, immunization • focused development of new agents, diagnostics, and strategies • regulatory/label guidance, prescribing, and advert restriction • audit of evaluation of intervention and compliance. the objectives of most strategies and policies are to better control antibacterial use with the intent of reducing or preventing antibacterial resistance. this, accompanied by parallel activities to monitor and understand resistance (such as its consequences and relationship to antibiotic use), improve infection control, and development of new agents (antibacterials and vaccines) and therapeutic approaches, is hoped to provide a sustainable solution in combating bacterial infection. carbon et al. ( ) state that these recommendations rightly focus on controlling resistance in the community through surveillance of resistance and usage, and education of prescribers and the public in judicious antibiotic use. nevertheless, the authors point to the need for more research to fill substantial knowledge gaps, notably the reversibility or containment of resistance with the optimization of antibiotic usage has yet to be definitely established davey et al., ) . it is suggested by carbon et al. ( ) that for now, antimicrobial management programmes should focus on ensuring the most appropriate use of antimicrobials rather than simply on limiting choices. interventions must also be audited for effectiveness/cost . it is also suggested that the programmes in the recommendations can not succeed if they do not imply the active contribution of health professionals, politicians, consumers, and pharma, and that the creation of optimal conditions for this type of cooperation is of critical importance chahwakilian, ) . the key role of pharma in these strategies is to deliver new antibacterials, although the cumulative impact of the parallel recommendations may present significant barriers to achieving this aim ( figure ). surveillance programmes of bacterial susceptibility have become commonplace in the field of antibacterials over the last decade and feature in most recommendations and policies relating to combating resistance. the principles of surveillance, key studies, data, and issues have been extensively reviewed (bax et al., ; felmingham et al., ; hunter and reeves, ) . good quality surveillance methodology and interpretation are essential to the understanding of resistance emergence and its control. the main functions for surveillance were described by felmingham et al. ( ) as: • quantification of resistance: resistance prevalence/distribution/changes over time • guidance for antibiotic use: individual patient level/guidelines/policies • research/education: epidemiology of resistance/link with usage • industry: r&d/licensing/marketing/post-marketing • resistance control: design of strategies/impact of strategies/interventions. pharma is both a generator and user of surveillance. additionally, all the functions for surveillance described by felmingham et al. ( ) have the potential to impact pharma's development strategies and potential success in delivering new antibacterials. the relationship between resistance, antibiotic usage patterns, and clinical outcomes is an important factor in determining policies for antibacterial use. scientifically robust methodologies and interpretations are critical but have not yet been fully defined or attained for many surveillance studies (bax et al., ) . pharma itself has been actively involved in the initiation and support of a number of key surveillance studies over many years (felmingham et al., ) . these studies are mostly aligned with the companies' discovery and marketing interests but nevertheless have provided good quality data in many cases where data were lacking and even pre-date the recent calls in strategy and policy documents for antibacterial surveillance. indeed, global studies, such as the alexander project (felmingham et al., ) , initiated in and funded by smithklinebeecham (now glaxosmithkline) pioneered the standardization and quality control of methodology across countries and laboratories in the surveillance of bacterial resistance in community-acquired lower respiratory tract infection and provided a model for a number of subsequent global and national studies. pharma involvement and funding in surveillance may be a continuing necessary and desirable role. pharma need data from which to establish and drive the need for r&d activities into new antibacterials. surveillance data are also needed for product labelling, such as the resistance prevalences required, for example, by emea. susceptibility data from surveillance are important to support product differentiation and benefits in the market place, and may also be required as part of a phase iv regulatory commitment for a new agent. academia and policy-makers also need such data to assess the antibacterial environment and the appropriate policy and practice interventions and outcomes. all parties need good quality, scientifically valid data. however, there may be differences in needs regarding the scope of studies, such as the organisms that are included, the agents tested, or the reporting of data (minimum inhibitory concentrations vs susceptible/intermediate/resistance), but the demand for quality and accuracy of interpretation should be equal. a key issue is the source and sustainability of funding of surveillance, along with ownership, interpretation, and dissemination of data. global or regional, longitudinal surveillance studies are extremely expensive and resource intensive. individual pharma companies have initiated and solely sponsored studies to support the development and marketing of new agents (bax et al., ; felmingham et al., ; hunter and reeves, ) . this creates a situation where at a particular time a number of pharma companies may compete for collecting centres for key isolates and be funding a number of laboratories to screen similar isolates and agents while at other times or for other pathogens or agents, there may be little pharma support, or data available from any source. surveillance funded by government, societies, or other non-pharma sources may not meet pharma's specific needs. conversely, pharma's studies may not meet broader needs (bax et al., ; lewis, ) , or be perceived as "distorted" source of data because they are funded by pharma (lewis, ) . pharma support for large single-sponsored surveillance studies is dependent on successful product registrations and marketing. similarly, pharma support for broad regional and national studies, of value to strategists and policy-makers in these areas will become limited in an environment of reduced investment and commercial success. collaborative surveillance between and within pharma and academia or regulators may become increasingly necessary but is difficult to implement in terms of mutually acceptable objectives, scope, methods, timelines, funding agreement, management, and publication/presentation rights. bax et al. ( ) stated that consortium funding will be necessary for large schemes to be successful, and that there is no "ideal" surveillance system. new approaches to the funding, conduct, and availability of surveillance data while recognizing individual pharma confidentiality and commercial interests, include the purchasing of surveillance data from commercial surveillance companies or entering into collaborative surveillance studies with specific protocols. sources of purchased data, such as from focus technologies (formerly mrl/tsn) (bax et al., ; hunter and reeves, ) , may provide solutions to many requirements although the extent, quality, and utility of the data is dependent on the database and may not be as well defined or specific for a purpose as a pre-defined protocol. examples of collaborative predefined protocols are the british society for antimicrobial chemotherapy (bsac) surveillance projects for respiratory tract pathogens (reynolds and bsac extended working party on respiratory resistance surveillance, ) and bacteraemia pathogens in which a number of pharma sponsors support a core protocol and panel of antibacterials, along with the ability to have research agents tested under confidentiality. the results from the core protocol, which has been developed by experts in academia, specialist testing laboratories, and pharma are made available via the website to the bsac membership (www.bsacsurv.org). this approach, combining support from a number of companies, with the wide and timely dissemination of core data resolves some of the issues and conflicts relating to quality, interpretation, and dissemination associated with single-company studies and also is hoped to increase sustainability. the current utility of this programme is, however, restricted due to the data and methods being specific to the united kingdom. in conjunction with the generation and use of susceptibility surveillance data, there is need for a clear understanding of the limitations, validity, and consequences of studies to correlate antibacterial usage with resistance. the relationship between antibacterial usage and resistance is complex, and while there is a clear association between use and resistance, cause and effect has not been substantially defined davey et al., ) . there are a number of confounding variables that are important to consider in the interpretation of simple cause and effect (davey et al., ) . reversibility or containment of resistance with optimization (or reduction) of antibacterial usage has yet to be definitely established . consequently, policies designed to curtail or prevent antibacterial resistance based on reduction or change in antibacterial use need to be based on sound science and importantly, the objective of maintaining or improving patient outcomes. bax et al. ( ) concluded that for surveillance: . decisions need to be made regarding the critical populations to be monitored for both local and national comparisons of resistance rates, that is, what level of resistance warrants intervention, and what should be the nature of the intervention; . quantitative data are more valuable than qualitative data and all testing must be shown to yield results that are capable of valid comparison; . molecular techniques should be used to define strains and detect mechanisms of resistance (see poupard, chapter ); . there is a place for both narrow focus and broader surveillance studies: both require funding, but broader studies, including a wide range of organisms and compounds, require consortium funding. there is a need for the interested parties such as academia, policy-makers, regulators, and pharma to consider mutually beneficial surveillance programmes, with agreed methodologies and interpretations persuant to their purpose. this approach may not only provide efficiencies in utility, support, and sustainability but also a better understanding of relationship between antibacterial use and resistance and the role and impact of policies and interventions. in addition to the key influential recommendations described by carbon et al. ( ) there are many other national and local guidelines, guidances, policies, and educational campaigns which impact antibacterial use. most such policies either describe the need for implementation of "judicious" or "prudent" use of antibacterials, or use terms such as "misuse" and "overuse" as causes of resistance and imply that a reduction in antibacterial prescribing per se will have a beneficial and sustainable effect on resistance. there is a recognition that while prescribing guidelines and other prescribing support systems should help control bacterial resistance in the community, their actual effect on resistance patterns is largely unknown (finch and low, ) and the reversibility or containment of resistance with the optimization of antibiotic usage has yet to be definitely established davey et al., ) . davey et al. ( ) described the control of antibiotic prescribing as a crucial part of any strategy to limit the development of resistance as advocated by the uk house of lords recommendations and the copenhagen recommendations . these authors recognized the difficulty in proving that antibiotic policies help to resolve a problem of resistance that has already developed and also recognized the greater difficulty in proving that policies prevent the development of resistance. most policies (and guidelines) are concerned with which antibiotic is prescribed and davey et al. ( ) state that it is more likely that development of resistance will be contained by policies which also try to limit unnecessary prescribing of antibiotics (i.e., prescribing for non-bacterial or self-limiting illness). the general advantages of an antibiotic policy are described by davey et al. ( ) as: • promotion of awareness of benefits, risks, and cost of prescribing • facilitation of educational and training programmes • reduction of aggressive marketing by pharma • encouragement of rational choice between drugs based on analysis of pharmacology, clinical effectiveness, safety, and cost; and specifically to antimicrobials as: • the promotion of education on local pathogen epidemiology and susceptibility along with awareness of infection control. the general benefits are described as: • improved efficacy of prescribing (sensitivity and specificity) • improved clinical outcome • reduced medical liability; and specifically to antimicrobials as: • limited emergence and spread of resistance. davey et al. ( ) suggest that antibacterial policies can definitely improve the quality of prescribing and may be used to limit cost and that limiting superinfections and antibiotic resistance should be viewed as additional benefit (and probably not a realistic primary aim). similarly, ball et al. ( ) stated that when prescribing is necessary, quality prescribing may not only combat resistance and optimize patient outcomes but also provide cost benefits. in a review of the impact of guidelines in the management of communityacquired pneumonia, several studies were identified which showed that an increase in the proportion of patients who receive prompt, appropriate therapy was associated with improvements in outcome measurements such as mortality and length of hospital stay (nathwani et al., ) . gould undertook a review of the role of antibiotic policies in the control of antibiotic resistance, noting that the pragmatic and essential approach to the control of antibiotic resistance is to control antibiotic use (gould, ) . he also noted that policies can be efficacious in reducing costs and levels of antibiotic use, but the subject of debate is whether antibiotic control measures can reduce current levels of resistance rather than just halting it. there are examples where control of antibiotic use has reduced the incidence of outbreak and resistant organisms in hospitals and similar examples where reduction of prescribing in the community has led to a degree of control of resistance. there are a number of confounding factors which make it difficult to attribute cause and effect entirely to reduction in antibiotic prescribing (davey et al., ; gould, ) . mathematical modelling seeks to take these factors into account and, while also casting doubts on whether reduction alone will prevent or reduce resistance (austin et al., ; gould, ) , may help with future understanding of measures which contribute to or reduce antibacterial resistance, and as such should be encouraged. use of this approach to define policies has been limited (if used at all) (davey et al., ) . nevertheless, policy decisions should be supported by evidence, and not just by concerns about future development of resistance or the desire to reduce costs (davey et al., ) . importantly, appropriate use of antibacterials needs a clear definition. it is recognized that recommendations and guidelines should emphasize that the role of antibacterials is for treating bacterial infection, when known or suspected (ball et al., ; davey et al., ) . use of antibacterials outside of this scenario is unnecessary, contributes to overuse and is an avoidable risk factor in the development of resistance (ball et al., ; davey et al., ) . however, when use of antibacterials is warranted (necessary) to treat bacterial infection, such use may also be inappropriate or suboptimal in terms of choice of antibacterial, dose, or duration. for example, schlemmer ( ) concluded that antibiotic misuse does have an impact on promoting antibiotic resistance, and that antibacterial choice, dosage, dosing regimen, or duration of therapy must also, therefore, be considered. carbon et al. ( ) suggested that, for now, antimicrobial management programmes should focus on ensuring the most appropriate use of antimicrobials rather than simply on limiting use or choices. a consensus group (ball et al., ) has recently identified principles for appropriate prescribing of antibacterials in lower respiratory tract infection with which to underlay prescribing and guideline formulation. these principles include: • identification of bacterial infection by optimized diagnosis • severity assessment where relevant • recognition and incorporation of ambient resistance data • targeting bacterial eradication (or maximal reduction in bacterial load) • use of pharmacodynamic (pd) indices to optimize choice and dosage • objective assessment of true (overall) costs of resistance and related treatment failure. guidelines, policies, and educational campaigns should seek to better define, support, and implement appropriate use based on principles such as those from the consensus group (ball et al., ) . "prudent" use or reduction in use alone will not adequately define or ensure optimum or appropriate use of antibacterials. the definition and implementation of appropriate prescribing based on evidence-based optimization of quality antibacterial use (right drug/dose/duration based on pd indices and local resistance patterns), rather than reduction in quantity alone may contribute towards the aim of slowing or preventing the emergence of antibacterial resistance, and also offer associated cost and efficiency benefits. importantly, this approach may also maintain an environment that supports the use of new effective antibacterials and a commercial rationale for investment and development by pharma. an ill-defined environment, focusing on the need to reduce quantity with little differentiation between optimal and suboptimal agents is not conducive to the development and marketing of agents with improved activity and efficacy benefits. increasing development costs and hurdles and shrinking market sizes, means that pharma has to get more value out of the r&d investment by improving productivity, reducing development timelines, reducing risk, and increasing the value of agents progressed to market. in the case of antibacterials, the situation is compounded by increasingly demanding regulatory policies affecting the activities required to secure product registration, the product label and clinical use (shlaes and ryan, ). the extent and success of antibacterial research has declined (idsa, ) and is partly a reflection of its relatively low commercial attractiveness compared to other therapeutic areas. the relative return on investment (roi) or net present value (npv) of antibacterials is a reflection of the market size and chance of success in capturing a commercially acceptable part of that market. this important "market share" will be a reflection of the properties and utility of the agents along with the success of marketing activities. differentiation of comparative benefits, such as efficacy against resistant organisms, broader spectrum of pathogens for a given indication, superior efficacy over commonly used treatments, improved dosage regimens and compliance, or better safety characteristics are important features in marketing an antibacterial and in the acceptance and uptake by policy-makers and in the demonstration of cost-benefits to formularies. policies or guidelines which decrease the ability of pharma to demonstrate these benefits, reduce the chance of gaining differentiated label indications (such as the inclusion of resistant organisms), or restrict usage to limited indications (such as only to resistant organisms) will negatively impact npvs and rois for new agents. development of an antibacterial agent for restricted use only may not be a commercially attractive proposition for pharma companies with interests in other therapeutic areas. in order for pharma to succeed and maintain investment, hurdles in productivity in discovery and development need to be overcome and the key issue of roi based on product benefits and use needs to be addressed. although policies themselves do not directly impact upon the process of discovery of new antibacterials, they do have a cumulative negative impact on the chance of success of developing and marketing new differentiated antibacterials and consequently, the willingness of companies to initiate or continue investing in antibacterial discovery research. the urgent need for new classes of antibacterials has, however, increased the pressure in pharma to maximize efficiencies in identifying new molecular targets for antibacterials and compounds active against those targets. genomics and high-throughput screening (hts) offer important potential advances in this area. on april francis crick and james d. watson published their paper "molecular structure of nucleic acids" in nature (watson and crick, ) the role of genomics in antimicrobial discovery should be considered against the background of pharma's efforts over many years in fine-tuning the existing classes of antibacterials to improve their spectra, efficacy, and safety through semisynthetic and wholly synthetic chemistry approaches. linezolid, an oxazolidinone, represented the first novel compound class introduced to the market in more than years (diekema and jones, ) . traditional chemical modification to produce new members of existing classes has resulted in significant improvements in ␤-lactams, macrolides, and fluoroquinolones (e.g., rasmussen and projan, ) , but has been a relatively slow and labourintensive process with limited additional success in recent years. a team of bench chemists in the s might produce up to novel compounds each per annum for biological screening against a panel of target organisms, resulting in a total, perhaps of hundreds of compounds being screened. for example, methicillin, discovered in had a beecham research number of brl , and was followed by many valuable semisynthetic penicillins over the next decade, notably ampicillin (in (in ), carbenicillin ( (in ), and amoxicillin, designated brl (in ( , indicating the extent of synthesis and screening of this highly successful semisynthetic range of compounds, at approximately per year. unfortunately, this approach of chemical modification based on knowledge of structure-activity relationships combined with improvements in throughputs of screening has failed to increase the number and diversity of antibacterials in recent times. mills ( ) describes genomics-related technologies as they are currently applied to the discovery of small molecule antibacterial therapies. with respect to microbial genomics, the dna sequence of haemophilus influenzae was published in (the first free-living whole-organism sequence), followed by mycoplasma genitalium and many other sequenced complete bacterial genomes, of which are publicly available, including those of more than human pathogens. the process of antibacterial discovery through genomics revolves around the "minimum gene set for cellular life hypothesis" (koonin, ; mills, ) and a number of defined stages in the process. (a) genome-scale transposon mutagenesis to identify all non-essential genes (inferring essential genes); (b) expression of anti-sense rna to probe suspected essential genes, and knocking out conserved genes of unknown function to identify novel "broad-spectrum" essential genes. . identification of target genes: (a) select target gene either as narrow-or broad-spectrum by specific conservation profile based on comparative genomic analysis; (b) prove essential for in vitro growth, for example, by gene knockout in relevant bacteria; (c) clone and sequence gene and optimally express protein product; (d) purify and develop assay, and screen and identify target inhibitors "hits"; (e) characterize hits in terms of potency, mechanism of action, spectrum, and selectivity. for broad-spectrum targets a key issue is to study isozymes from several genetically diverse bacterial species along with further screening against a panel of microbes for cellular activity, particularly to address the potential role of intake cell membrane barriers or efflux mechanisms (mdrs) on antibacterial activity. lead compounds can be further optimized in terms of potency, spectrum, and selectivity through studies on the mode of action (moa). optimization of pharmacokinetic (pk) and pd properties through distribution, metabolism, and pk (dmpk) studies and drug delivery/formulation are increasingly important areas in the development process. in particular, knowledge of the role of pk/pd in relation to appropriate dosing and the potential for resistance development is evolving and is being used increasingly by pharma. the proof of principle of this genomics-driven, target-based approach, starting with a conserved gene and leading to antimicrobial compound is the discovery of bb- , a peptide deformylase inhibitor with gram-positive and gram-negative activity. optimization by hts is exemplified by methionyl trna synthetase. a target identified through genomics and genetics and to which whole-cell screening of target-specific inhibitors has been undertaken is lpxc, a metallo-enzyme essential for growth of gram-negative bacteria. high-density dna microarrays is a technology undergoing validation which has the potential to generate a vast amount of functional information on coordinated gene expression under various growth conditions. there are a number of new antibacterials currently in late-stage development, although all of these are from existing established classes (e.g., penem, fluoroquinolone, glycopeptide, lipopeptide, glycylcycline) (rasmussen and projan, ) . it is hoped that use of genomics to identify novel targets with biological and clinical relevance and hts to increase the chance of "hits" may result, in time, in a range of novel antibacterials for development (mills, ; rasmussen and projan, ) . many, if not all, of the bacterial targets have now been identified, but hts has yet to deliver the range of novel antibacterial compounds that hit these targets. encouragingly, the most advanced hts plants now have the capacity to screen , compounds per day. worryingly, there are increasing hurdles in the development and commercialization of antibacterial agents that might adversely impact the willingness of companies to initiate or continue investing in antibacterial discovery research. new antibacterials are unlikely to be recommended as first-line clinical agents in policies designed to control antibacterial use unless they offer benefits, often assessed in relation to cost over existing branded or generic agents. efficacy against organisms resistant to other antibacterial choices is a potential benefit but if it is the sole indication it may be of limited commercial attractiveness. there are a number of significant hurdles in being able to demonstrate and use differential benefits. these relate to governmental/ regulatory policy with respect to clinical development, product labelling, and promotion. shlaes and ryan ( ) reviewed the strategic and regulatory considerations in the clinical development of anti-infectives. a new and evolving set of challenges exists for pharma in the clinical development of antibacterials with a number of requirements from existing or proposed regulatory guidelines posing significant hurdles and complexity. the key points of concern to pharma are listed below. . removal of in vitro activity from product label (fda)-limits potential for description of agents' full spectrum of activity (such as against rare or bioterrorism pathogens), differentiation and promotion. . post-marketing surveillance of resistance and label updates (as required (fda and national eu agencies) )-presents "unlevel playing field" with established/older products. . requirement for in vitro percentage susceptibility of organisms from eu countries (committee for proprietary medicinal products [cpmp])requires product-specific broad surveillance (organisms and geography). . powering of clinical trials to % non-inferiority powered at % level (fda, cpmp)-substantially increased patient numbers and cost. . placebo-controlled superiority trials requested for acute otitis media and acute exacerbations of chronic bronchitis (fda, cpmp)-increased patient numbers and increased risk of not achieving relevant outcomes. . paediatric rule (fda); the requirement to progress paediatric indications/ registration-increased or earlier resource/cost for paediatric studies. . specific indications, for example, pharyngitis, otitis media, rather than upper respiratory tract infection (fda, cpmp)-larger number of phase iii randomized controlled comparator studies required to achieve a broad label. . bacteriological study populations and endpoints requirements (fda, cpmp)-bacteriological endpoints required for breakpoints, labelling, and differentiation. . national comparators and resistance in eu (cpmp)-additional studies needed to address national comparators. the regulatory guidelines are increasingly focusing on the need for demonstrations of non-inferior clinical efficacy in randomized controlled trials in the specific indication. in the united states, inclusion in the product label of only those organisms isolated from the indication under study and for which clinical cure was achieved is proposed, irrespective of the in vitro activity spectrum. label indications are a key point to control antibiotic use (schlemmer, ) and any information given to the prescriber that is able to help select for proper indications is potentially an important tool for good antimicrobial practice (schlemmer, ) . however, schlemmer ( ) also states that there is a critical need for trials to select for those patient populations who really need antibiotics, or to look for new endpoints able to differentiate between drugs, rather than only demonstrating equivalence. this approach may ensure that clinical evidence supports the claim for beneficial activity against a particular organism in a particular indication, or population, but inevitably will restrict the breadth of label. the commercial implications of limited labels based on proof of superior benefits (and not just equivalence), compared with broader labelling based on equivalence will be critical to pharma. the value of studying new endpoints for differentiation will also be dependent on acceptance of the endpoints by regulators, and their incorporation into product labelling, enabling promotion and communication. the differential benefits would also need to translate into guidelines and formulary inclusion. it has been argued by monnet and sorensen ( ) , that antimicrobials that represent real innovations are readily accepted by hospital prescribers and naturally gain market shares. the hurdle is in being able to demonstrate the innovative benefits to the satisfaction of the regulators and decision-makers, and in there being sufficient commercial return from use in a narrow-defined patient group. a particular issue is that there will be significant hurdles in the ability of pharma to demonstrate clinical efficacy against emerging resistant organisms, which may only rarely be isolated in clinical trials. pk/pd data which allow predictions of bacteriological efficacy to be made and tested, for example, in in vivo infection models of simulated human pk, or in small pd studies in patients, have been proposed by a number of bodies, including the eu cpmp (emea). however, the use of such data has yet to be fully accepted and adopted by the fda as a surrogate for clinical efficacy and breakpoint determination. pk/pd data are of particular interest when trying to define the best dosage and dosing regimens for new compounds. as the bacteriological endpoint correctly defines the outcome in an infectious process it would serve to assess the pk/pd relationship of a drug (schlemmer, ) . using pk/pd data to predict bacterial eradication or clinical outcome should be considered as the only way to select for optimal therapeutic regimens regarding antibiotic choice and dosing regimen as well as determining the optimal therapy duration (ball et al., ; schlemmer, ) . a greater role of predictive pk/pd data and modelling under certain circumstances and for specific target populations, has been proposed by cpmp (emea) and is supported in general by pharma. global pharma need to conduct clinical development programmes that satisfy the highest requirements of both fda and emea. in europe, there is a need to include comparative agents approved and relevant to individual eu countries, or for which a consensus justification can be argued, for technical approval (emea). phase iii clinical trials are designed primarily to meet the requirements of the regulators. however, these traditional comparative noninferiority trials fail to provide important evidence of potential benefits over existing therapies. with clinical success for antibacterials in the % or more level, demonstrations of superiority require vast patient populations. pharma rely on other data to indicate superiority and benefit, ranging from potency (minimum inhibitory concentrations, etc.), per cent susceptibility based on breakpoint, in vitro and in vivo models, pk/pd, and defined clinical studies to demonstrate bacteriological and health-outcome benefits. much of the clinical work undertaken to secure regulatory approval fails to best demonstrate the role and clinical benefits of new agents (bax et al., ) and yet is often used as the evidence base for reimbursement, guidelines, and policies. there has also been a proposal to update and harmonize antibacterial product labels between european countries, particularly for "old" antibiotics and their datasheets (summary of product characteristics) at the time of generic introductions because lack of relevant product information promotes inappropriate use (european conference on antibiotic use in europe, - november, ; schlemmer, ) . the burden of cost to provide new data to demonstrate the benefits of marketed and new agents would lie with the pharma r&d companies. failure to produce data to support current claims could result in removal of differentiation from established branded products, while provision of data may strengthen the labels of generic products. bax et al. at the whitley park symposium in reviewed the limitations of the current clinical evaluation process and stated that the lack of development in how to define precisely both drug value and appropriate use will seriously hamper the drug industry's ability to develop important new medicines discovered by new technologies (bax et al., ) . the authors suggested that what is needed is further and much more rapid development of conventional means of drug evaluation, such as the clinical trial, as well as visionary use of new methods in epidemiology, and new use of electronic data merged in a way that identifies drug effects on both a population and individual basis. the role of r&d-based pharma is to discover, develop, and commercialize antibacterials. there is a danger that the wide range of policies which have been introduced under the auspices of "combating resistance" will themselves hamper pharma's ability to deliver a key strategy, if not the most important weapon in the battle against bacterial infection and resistance, the introduction of novel antibacterials. policies and improvements in the quality of antibacterial prescribing have an important role to play, as do diagnostics, vaccines, infection control, and other interventions. pharma is clearly an important partner along with government, ngos, regulators, infectious diseases experts, practioners, and patients in the battle against bacterial infection. the "conflicts of interest between the prescriber, the regulator, and the profit maker" was the subject of a supplement to clinical microbiology and infection. the editor (gould, a) , recognized that the calls for restrained use of antibacterials to combat and control resistance counters the natural instincts of doctors to do the best for their patients and of pharma, which of necessity, needs to profit to exist and continue. it is, however, unfortunate that pharma can be regarded first as "profit makers" and can even be excluded from contributing to debates on the subject of antibacterial use (european conference on antibiotic use in europe, - november ) . there needs to be a distinction between companies which are solely suppliers of generic products and those who have the objective, dedication, and expertise to discover and introduce new antibacterials. these are undoubtedly profit makers, being subject to commercial and shareholder expectations, but perhaps should be considered foremost as "providers" with respect to new antibacterial solutions. gould describes an international partnership of medical societies and industry, in association with regulators as a model for the future in the battle against antibacterial resistance (gould, b) . schlemmer ( ) highlighted that while antibacterial policies were the keystone in promotion of good antimicrobial practice, more accurate and relevant information on antibiotics is urgently needed and that it is the responsibility of pharma and regulators to move together towards an improvement in antibiotic evaluation. the objective would be to give prescribers more critical product information and to help the experts create better guidelines. who included pharma via the international federation of pharmaceutical manufacturers association (ifpma) in consultation on their containment strategy and model prescribing guidelines (www.who.int/emc/amr.html) and the european federation of pharmaceutical industries and associations (efpia) have represented pharma in eu and emea discussions and consultations on clinical trial guidelines and labelling. in the united states a multiagency task force of fda, cdc and the national institute of health (nih) issued a document entitled public health action plan to combat antimicrobial resistance in with a priority to create an interagency antimicrobial resistance product development working group coordinated by the fda, us department of agriculture (usda), and cdc (shlaes and ryan, ) . a second priority was to, "investigate and act upon potential approaches for stimulating and speeding the entire antimicrobial resistance product development process, from drug discovery through licensing," including exploring the economics of the situation and incentives. while monnet and sorensen ( ) argue that much investment from pharma is into marketing and not r&d and that the so-called "r&d scare card" is not justified, it is clear that pharma companies are increasingly taking the commercial decision not to invest in r&d for antibacterials, but in other areas. according to shlaes and ryan, incentives for increasing pharma r&d into priority infectious diseases include the need for more information on the market and disease areas (based on market identification, disease-specific bioinformatic systems, development of surrogate endpoints), more predictability (based on market assessment, international regulatory harmonization, and reinforcement of intellectual property rights), and more cost-risk sharing (market creation, patent extension, orphan drug legislation) (shlaes and ryan, ) . a number of bodies, such as who, idsa, and eu task forces have begun processes to assess the situation and identify some areas of action. these include: • summarizing the value of antibacterials • identifying the status of clinically relevant resistance and priority pathogens • evaluating the state of antibacterial research/regulatory submissions/industry involvement and outlook • maintaining databases of funding agencies, their research interests, new opportunities for funding • documenting the vulnerabilities related to the manufacture of antibacterials/ shortages/negative impacts on public health: gap analysis • undertaking the identification, prioritization, and tracking of global public health needs (a global agenda) • reviewing/documenting government activities to foster development of new antibacterials • reviewing recommendations for "incentivizing" • modifying regulatory approval processes such as priority review, fast track, waiver of user fees, orphan drug status, modified/smaller clinical trials, and/or reduced number of efficacy studies per indication (and use of surrogates such as pk/pd) • harmonizing clinical trial methodologies and implementing coordinated action by regulatory agencies in registration of new products • increasing education and training opportunities. research-based pharma needs to be included as a partner in these collaborative initiatives in order to help shape the future in a way which will be conducive to continued investment into r&d for new antibacterials while improving their use and sustainability. this will require a full consideration of the contributing factors, actions, and impacts in order to find a way to maintain a critical balance ( figure ). a new model may need to be defined which explores alternative roles of small companies, government, and ngo bodies along with big pharma in the conduct and funding of antibacterial discovery, development, and distribution. policies are important and necessary in controlling antibacterial use in an attempt to preserve the utility of existing and future antibacterials. they should aim to minimize unnecessary and inappropriate use, as avoidable risk factors in the development of resistance, while maintaining or improving patient outcomes. the effect of antibacterial policies on the containment or reduction of resistance is largely unknown and should focus not on quantity of prescribing alone but on quality to ensure appropriate prescribing in terms of antibacterial choice, dosage, dosing regimen, or duration. policies that relate to figure . from the past to the future: hypothetical potential scenarios evolving from the relationship between antibacterial need/resistance, antibacterial productivity and policy. (a) sustainable balance of antibacterial productivity, resistance, and regulation/policy; oscillations may decrease over time with better understanding of the relationships and balanced management. (b) crisis of imbalance of increased policy/regulation, decreased incentives and antibacterial productivity and increasing/uncontrolled resistance. antibacterial use have the potential to reduce the antibacterial market size and commercial attractiveness relative to other therapeutic areas. policies that relate to development activities and labelling have the potential to increase development costs, restrict use, and limit the ability to differentiate benefits. collectively policies are negatively impacting big pharma's willingness to continue investment in this field. the combined and cumulative effects of the various policy items related to surveillance, use, clinical trial guidelines, product labelling, and promotion require a broad, collaborative, and global view of the impact on pharma r&d. collaboration is required to identify agreed and mutually acceptable ways to streamline development, implement appropriate prescribing, demonstrate and promote product benefits, and maintain financial incentives. antibacterial discovery, development, and use are related within a dynamic environment that includes bacteria, their resistances, and policies. as with any dynamic environment, change will alter the balance (figure ). policies are contributing to a change and a negative impact on the potential and willingness of pharma to develop new antibacterials. while change may require adaptation for survival and success, careful consideration and collaboration is needed by all parties to help to ensure that insurmountable hurdles are not created leading to the inability of pharma to survive and succeed in antibacterial r&d. failure of pharma to deliver new antibacterials would lead to "antibacterial extinction." pharmaceutical company approach bacterial resistance concerns the relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence surveillance of antimicrobial resistance-what, how and whither? antibiotic clinical trials-the witley park symposium moving from recommendation to implementation and audit: part . current recommendations and programs: a critical commentary politiques d'antibiothérapie a l'échelon national dans divers pays moving from recommendation to implementation and audit: part . review of interventions and audit antibiotic policies oxazolidinones: a review european conference on antibiotic use in europe. - surveillance of resistance in bacteria causing community-acquired respiratory tract infections a critical assessment of published guidelines and other decision-support systems for the antibiotic treatment of community-acquired respiratory tract infections the evolution of anti-microbic drugs a review of the role of antibiotic policies in the control of antibiotic resistance minimum antibiotic stewardship measures the current status of surveillance of resistance to antimicrobial agents: report on a meeting abstracts of the nd interscience conference on antimicrobial agents and chemotherapy abstracts of the rd interscience conference on antimicrobial agents and chemotherapy the future of antimicrobial drug availability: an impending crisis measuring the pace of new drug development in the user fee era how many genes can make a cell: the minimal-gene-set concept antimicrobial resistance surveillance: methods will depend on objectives the role of genomics in antimicrobial discovery the patient, the doctor, the regulator and the profit maker: conflicts and possible solutions do guidelines for communityacquired pneumonia improve the cost-effectiveness of hospital care? antibacterial drug discovery: what's in the pipeline? bsac respiratory resistance surveillance programme: first results of the winter - collection impact of registration procedures on antibiotic policies strategic and regulatory considerations in the clinical development of anti-infectives molecular structure of nucleic acids: a structure for deoxyribose nucleic acid figure . a question of balance: increasing and decreasing factors in the environment of antibacterial resistance, usage, discovery, and development. key: cord- -vgfv pi authors: hall, graeme m. j.; hollinger, david y. title: simulating new zealand forest dynamics with a generalized temperate forest gap model date: - - journal: ecol appl doi: . / - ( ) [ :snzfdw] . .co; sha: doc_id: cord_uid: vgfv pi a generalized computer model of forest growth and nutrient dynamics (linkages) was adapted for the temperate evergreen forests of new zealand. systematic differences in species characteristics between eastern north american species and their new zealand counterparts prevented the initial version of the model from running acceptably with new zealand species. several equations were identified as responsible, and those modeling available light were extended to give more robust formulations. the resulting model (linknz) was evaluated by comparing site simulations against independent field measurements of stand sequences and across temperature and moisture gradients. it successfully simulated gap dynamics and forest succession for a range of temperate forest ecosystems in new zealand, while retaining its utility for the forests of eastern north america. these simulations provided insight into new zealand conifer–hardwood and beech species forest succession. the adequacy of the ecological processes, such as soil moisture balance, decomposition rates, and nutrient cycling, embodied in a forest simulation model was tested by applying it to new zealand forest ecosystems. this gave support to the model’s underlying hypothesis, derived from linkages, that interactions among demographic, microbial, and geological processes can explain much of the observed variation in ecosystem carbon and nitrogen storage and cycling. the addition of a disturbance option to the model supported the hypothesis that large‐scale disturbance significantly affects new zealand forest dynamics. individual-based forest simulation models predict the dynamics and structure of complex forest ecosystems. worldwide, long-term forest composition and forest species distributions are under pressure from continuing large-scale anthropogenic effects. because forest simulation models are ecosystem based, they can provide both predictions of forest response to these impacts and a consistent synthesis of the ecological processes involved (rastetter ) . such properties make them a vital part of any assessment of ecosystem response to global change (reynolds et al. , shugart and smith ) . the structure of most simulation models of forest succession can be traced back to those developed to reproduce the population dynamics of trees in mixedspecies forests of northeastern north america (botkin et al. , shugart and west ) . this approach tracked the development of each individual plant throughout its life cycle, with forest dynamics simulated by calculating the competitive interrelationships among trees in a restricted area, similar to that resulting manuscript received april ; accepted january ; final version received march . from the gap in a forest canopy formed by the death or removal of a large canopy tree. by simulating a sufficient number of gaps, the dynamics of the forest are reproduced (yamamoto ) . this concept is supported by various plant succession studies, which show that changes in a forest ecosystem may be described by averaging the growth dynamics in gaps of different successional ages (watt , bray , curtis , forman and godron . forest gap simulation models have been developed to predict long-term impacts on forest ecosystems caused by blight, harvest management, past climates, animal browse, pollution, and large-scale disturbance by fire or storm, and to predict transients in species composition and forest structure due to changing climate, (e.g., shugart and west , aber et al. , solomon et al. , pastor and post , bugmann . shugart and smith ( ) compiled a list of such models developed to simulate vegetation dynamics in environments ranging from cool northern hemisphere boreal forest to warm subtropical australian rain forest. almost half of these models are dedicated to north american vegetation ( % of these in eastern forests), with the other models predicting forest composition and dynamics in central and northern europe, australasia, africa, and asia. comparisons have shown that a forest gap model developed for one geographical area is unlikely to contain all of the ecological processes required to successfully simulate forest composition and structure for another area . this is partly because, despite a common lineage, models formulate the basic processes of species establishment, growth, and mortality variously. models also vary by the way in which resource limitations alter growth, by the species' life history attributes employed, and by the depth of physiology incorporated. not all models explicitly maintain a soil moisture balance or a litter decomposition-soil nutrient cycle. in an effort to better determine the potential role of climate change and other exogenous factors on new zealand forest development, we extended an eastern north american simulation model (pastor and post ) for new zealand's forests. in doing so, we evaluated the ecological generality of functions and algorithms developed originally for the eastern north american forests, and gained insight into several longrunning debates about ecological processes in new zealand forests. the nature of new zealand's topography, climate, and forest characteristics indicated which ecosystem processes to model. new zealand's small group of islands (landmass km ) have variations in climate, geology, and soil that offer a wider range of habitats than many much larger landmasses (wardle , molloy ). the three main islands (north, south, and stewart) span km ( Њ) of latitude and have a maritime climate, with sea level temperatures ranging from warm temperate in the north (mean annual temperature (mat) ϳ Њc) to cold temperate in the south (mat ϳ Њc). new zealand is tectonically active, with mountain building continuing at rates of up to mm/yr (whitehouse ) . about % of the land is Ͼ m above sea level, and % is defined as hilly or steep (molloy ) . the varied topography cuts across the prevailing westerly winds, modifying land temperatures and causing strong rainfall gradients. the north island has a central volcanic plateau with an average elevation of m and main axial mountain ranges running northeast to south. rainfall exceeds mm/yr in these areas and can reach mm/yr. there are also sizable areas of lowlands and coastal plains. the south island has a young mountain range running km north to south. the many summits Ͼ m create strongly differentiated climatic gradients. in the eastern lee of the south island range, rainfall drops to a low of mm/yr, whereas on the windward side in westland and fiordland, it may reach mm/yr near the ranges. the forests of new zealand are dominated by longlived evergreen species (wardle , wardle . nothofagus (beech) species characterize many forest types, occurring either in pure associations ( % of the remaining forested area) or in mixed forest ( % of remaining forest area). beech species predominate in mountain regions of both main islands. their wide ecological ranges enable their frequent occurrence in montane zones as well as lowland areas. in the northern warmer areas (north of Њ s), the conifer agathis australis dominates the forests in association with a mixture of hardwoods, podocarp, and beech species. further south, lowland forests are characterized by emergent, long-lived, evergreen podocarp species dacrydium, podocarpus, and prumnopitys. these are associated with a diverse group of broad-leaved hardwoods (beilschmiedia, metrosideros, and weinmannia) , characteristic of the main canopy (ogden et al. ) . the strong rainfall gradients and dry summer climates influence species composition and led us to consider models with a site water balance (e.g., post , botkin and nisbet ) . the young landscapes and generally infertile forest soils in new zealand (molloy , wardle ) similarly required models that relate soil nutrient status to species composition and forest stature (e.g., aber et al. , pastor and post , bonan . we chose the linkages gap model post , post and pastor ) because it included these ecosystem processes without excessive data requirements. it has explicit feedbacks between light, water, and nitrogen availability, and their effects on stand composition and productivity. previous gap models have related soil nutrient status to tree growth by species-specific sigmoid equations that reach maximum values at the highest reported basal area, or biomass, for a given region. the linkages model eliminates these site-specific maxima by explicitly simulating water and nutrient availability and using them to influence tree growth (post and pastor ) . however, the model lacks some recent modifications in allometric relationships, growth equations, and spatially explicit modeling of the light environment (e.g., leemans and prentice , martin , pacala et al. , prentice et al. , bugmann . a complete description of linkages is given in pastor and post ( ) . our model, linknz, is a version of linkages generalized for new zealand forest conditions, with species parameters obtained from an alternative database of new zealand species (g. m. j. hall and d. y. hollinger, unpublished manuscript) . here, we examine how well linknz simulates forest patterns and reproduces forest characteristics in a range of broadleaved hardwood and conifer forest types throughout new zealand. the model presented is intended as a basis for future development. some characteristics of new zealand tree species differ profoundly from those of eastern north american species. therefore, we were careful to extend, rather than modify, the mechanisms of competition or nutrient cycling. this preserved the model's original ability to reproduce dynamics of the forests of eastern north america and allowed a com-generalized forest gap model parison of results with linkages. our intention was to produce a more generally applicable forest gap model. the linkages model post , ) shares a common structure with the jabowa/foret class of stochastic tree population models that predict ecosystem dynamics through interactions between the forest and available resources (botkin et al. , shugart and west ) . the model simulates, on a yearly cycle, the establishment, growth, and mortality of all individual trees in a / ha plot ( . ha), adjusted by the effects of climate, soil properties, and competition. plot size corresponds to the average gap created by a dominant tree in eastern north american forests (shugart and west ) . initial diameter at breast height (dbh) is stochastically set between . cm and . cm. monthly rainfall and temperature variables, together with soil moisture capacity and wilting point, determine available site moisture. as the canopy forms and develops, light availability to each tree changes, affecting growth rates and the establishment of new trees. available soil nitrogen is initialized for the site and then determined annually by external inputs, losses due to leaching, and dynamics associated with processes of immobilization and mineralization during litter decomposition (post and pastor ) . available soil nitrogen then affects tree growth and stand composition, which, in turn, alters litter quantity and quality and modifies decomposition rates (pastor and post ) . a sufficient number of growing seasons, or annual cycles, was set to allow modeled forest biomass at each site to settle into an approximate steady state. the longevity of several widespread, dominant new zealand tree species (g. m. j. hall and d. y. hollinger, unpublished manuscript) led us to run the model for annual cycles, rather than the - considered sufficient for eastern north american species by pastor and post ( ) , or the -yr period used by pacala et al. ( ) . we retained this -yr time frame when simulating stochastic whole-stand disturbances, to allow long-lived individuals in any undisturbed stands to complete at least one life cycle. the stochastic nature of the model requires that more than one plot be simulated to obtain an adequate description of forest composition and structure (yamamoto ) . we generated plot successions on each site to smooth anomalous events. because of its linkages heritage, linknz also tracks details of soil organic matter and nitrogen pools, as well as site water balance. typically, both soil organic matter and soil n accumulate on a plot for several centuries until reaching an approximate steady state. by contrast, the estimates of transpiration depend only on the physical environment. these outputs assist in the understanding of factors regulating vegetation at different sites, but insufficient new zealand data prevented further evaluation. latitude, monthly temperature, monthly rainfall, and growing season data were obtained from new zealand meteorological service climate reports ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . soil moisture holding capacity and wilting point were set according to broad soil type and soil moisture deficit maps (molloy ) , and knowledge of the seven test sites. the initial organic matter ( . mg/ha) and n levels ( . mg/ha) were left as the model default values. we selected tree species considered fundamental to the structure and functioning of new zealand native forest ecosystems, using a reference file of all woody species found on surveys (hall ) . these species included early successional species, understory species, and many major canopy species occurring throughout new zealand forests. we also included four common and widespread tree fern species, cyathea smithii, c. dealbata, c. medullaris, and dicksonia squarrosa, because of their influence on patterns of succession in new zealand forests (wardle ) . they are treated by the model in the same way as tree species. optimal growth constants were calculated from the equations of botkin et al. ( ) from species maximum dimension and longevity. species used are listed in the appendix. model parameters generated from the species' life history attributes included maximum height, maximum diameter, maximum longevity, limits of annual growing degree-day sums, shade and nutrient tolerances, establishment conditions and rates, and various canopy, foliage, and litter properties. data and methods of obtaining parameters are described in g. m. j. hall and d. y. hollinger (unpublished manuscript) . the linkages model, as presented by pastor and post ( ) , required modifications to its slow-growth, available-light, and decay-rate conditions to reproduce forests characteristic of new zealand sites. many major forest species did not feature in the simulations. for example, at riverhead near auckland, linkages limited species composition to the large conifer agathis australis and two hardwoods, beilschmiedia tawa and b. tarairi, and excluded the common podocarp species dacrydium cupressinum, prumnopitys ferruginea, and p. taxifolia. further south at taupo, linkages predicted that the hardwood b. tawa would dominate and exclude all the common podocarp species. this pattern was repeated at other sites throughout the country, with site occupation being captured by one or two hardwood ecological applications vol. , no. or beech species and other widespread species failing to establish. the linkages model tests the growth of a tree independently of age and employs conditions common to many other models. if the resource-limited diameter increment is less than a fixed minimum of mm/yr (botkin et al. , shugart , botkin and nisbet , or Ͻ % of the maximum increment for its size (solomon ) , the model defines this as a poor growth year for the stem. if a tree grows poorly for two consecutive years, the probability of survival is reduced so that it has a Ͻ % chance of surviving consecutive years of poor growth. this ''poor-growth'' condition is too restrictive for modeling several slow-growing new zealand species. the clearest case is that of the long-lived conifer halocarpus biformis, with a highest recorded growth increment of . mm/yr (wardle ) , preventing linkages from establishing it at all. under link-ages, the widespread, dominant conifers of the podocarpaceae with recorded maximum annual diameter increments Ͻ mm/yr also struggle to survive in slightly less than optimal conditions. slow growth is common in the understory for other new zealand species as well. seedlings of nothofagus species, for example, remain in a quiescent state (Ͻ . m tall), making only limited growth for decades until an opportunity is provided by the death of canopy trees (wardle ) . nothofagus fusca, normally one of the faster growing dominant species (stewart and rose ) , may grow in diameter by only . mm/yr under a dense canopy, with % of the poles in a typical stand passing through this stage (kirkland ) . baxter and norton ( ) show a similar growth release behavior for dacrydium cupressinum and quintinia acutifolia, in which ring widths of young trees are Ͻ . mm/yr under an intact canopy, but increase to widths of - mm/yr after the overstory trees are removed. to minimize alterations to the model, we retained the same slow-growth conditions of linkages when maximum diameter increments exceeded . mm/yr, or when maximum longevity was attained. for maximum increments Ͻ . mm/yr, growth was defined as slow only when resource-limited increments were Ͻ % of the maximum increment. the . mm/yr threshold was chosen by comparison against optimal growth increments recorded for a range of new zealand tree species (g. m. j. hall and d. y. hollinger, unpublished manuscript) . species with a maximum diameter increment exceeding . mm/yr will have, at some point, the same tests for slow growth as in linkages, whereas those that never attain this increment have the mm/yr fixed minimum waived. these conditions allowed the slowest growing species, including several in the podocarpaceae, to establish and move through the slowgrowing phase without excessive mortality. the light passing through a canopy can be modeled, using the beer-lambert law, as where i is the light intensity below the canopy; i o is the light intensity above the canopy; k is an extinction coefficient that is a function of foliage angle distribution, spatial dispersion, and optical properties; and lai is the leaf area index in square meters of foliage per square meter of ground (monsi and saeki ). the linkages model calculates i as a percentage of full sunlight. this value is used to determine whether there is sufficient light for new individuals to become established on the plot, and as a growth multiplier for seedlings of those species that can establish. in link-ages, it is calculated (aber et al. ) as: where f is the foliage mass in grams per plot, and the divisor is a factor that accounts for the size of the plot ( . m ) and converts the mass of the foliage into an effective leaf area index. the per meter conversion factor of . ( / . ) is thus the product of the leaf mass per unit area (slm) and the reciprocal of the extinction coefficient, k. whittaker et al. ( ) used a value of ϳ g/m for northern hardwoods foliage, implying that the implicit value of k from aber et al. ( ) is ϳ . . new zealand forests are predominantly evergreen, with high specific leaf mass, in contrast to the predominantly deciduous eastern north american forests. consequently, linkages underestimates available light in new zealand sites for a given foliage mass, with the result that canopy species prevent any new establishment. we rewrote eq. as to take account of the variation in slm, which was an implied constant in linkages, and then used our measured slm values. within linkages, canopy openings are assumed to increase decay rates because of microclimatic changes. the model relates closed-canopy leaf production, l c , to available water for plant growth, w s (pastor and post ) , as it then compares this year's leaf litter (l a ) with l c to construct a decay multiplier that increases decomposition under canopies with low leaf area (aber et al. ) . for soils of high water-holding capacity, the multiplier ranges from . (l a ϭ l c ) to . (no canopy); for low water-holding capacity, it ranges from . to . (pastor and post ) . in linkages, the l c value for canopy leaf pro-duction is too low for most new zealand forests; l a exceeds l c , causing the model to set the decay multiplier to . and so nullify any gap effect. field examples show that daniel ( ) estimated l c as . mg·ha Ϫ ·yr Ϫ in a new zealand podocarp-broad-leaved forest; benecke and evans ( ) established that l c ϭ . mg·ha Ϫ ·yr Ϫ from a nothofagus truncata forest; and hollinger et al. ( ) obtained l c ϭ . mg·ha Ϫ ·yr Ϫ from a mature n. fusca stand. leaf production may be greater in new zealand forests because of a long growing season, combined with the evergreen habit of most tree species. over a -yr run of the model, simulations at a warm-temperate species-rich forest site at riverhead, auckland showed that the original decay multiplier was nullified in . % of years on soils of low water-holding capacity, and in . % of years on soils of high water-holding capacity. to compensate for differing new zealand forest leaf production values and to retain eq. for american species, a scaling factor was applied to l a . this was obtained by multiplying each plant's litter mass by the average northern hardwood foliage mass of g/m (whittaker et al. ) and dividing by the species' slm. over the simulated period, the model calculated mean values for l a of . mg·ha Ϫ ·yr Ϫ on low-water-holding capacity soils and . mg·ha Ϫ ·yr Ϫ on high-capacity soils. the slm adjustment rescaled these mean values downward by nearly %, making them comparable with the l c of old-growth american forests in eq. , and activating the decay rate multiplier in new zealand forest sites. after this adjustment, the decay-rate multiplier on the simulated riverhead forest plot was negated on just . % of the annual cycles. pollen, charcoal, and fossilized plant fragments point to a long history of change in new zealand indigenous forests. forest disturbances have been due to physical factors associated with steep mountain slopes, and include volcanism, periodic fire, forest dieback, windthrow, drought, flooding, and snow damage (wardle ) . we added a basic mechanism to linknz to simulate disturbance. the type (wind or fire) and the mean disturbance return time can be set in the site parameters. the linknz model will trigger that type of disturbance with a probability annually that is the reciprocal of the disturbance frequency. after windthrow, all trees on the plot are assumed to be dead and all biomass, including belowground root mass, is returned to the site for decomposition-nutrient cycling. after fire, all trees are assumed to be dead and the larger biomass components are returned to the site. the biomass and n in foliage and twigs are presumed to be volatilized and lost from the site. revisions made to the linkages code (pastor and post ) gave a threefold improvement in execution speed. the linknz program, species data, and site data will be made available, subject to a ''fair use'' policy, on the web site ͗http:/www.landcare.cri.nz͘. evaluation of forest ecosystem gap models is not straightforward. to construct definitive tests of simulated forest dynamics, several stands would have to be monitored for long periods while they were returning to old-growth forest. even in well-observed eastern north american forests, a lack of historical data on succession has been acknowledged (pacala et al. ). in addition, rastetter ( ) has noted that each alternative used to evaluate modeled ecosystem response to global change fails to provide a severe and crucial test. partly, this is due to difficulties in locating past or present ecosystem states comparable to those expected under climate change. for instance, how can valid data be obtained for evaluating long-term vegetation responses to increased co , when short-term chamber experiments are still inconclusive? we adopt recent evaluation methods for forest gap models to evaluate the ability of the model under current climates, but acknowledge that theoretical difficulties remain. shugart ( ) and shugart and smith ( ) discuss procedures used for testing the results of gap models. most include assessing the model's abilities to reproduce ''target patterns'' of stand or tree biomass increments, stand structure (basal area, density, stem diameter distributions) or composition (relative basal area, relative density) for stands of known age, successional trends in a chronosequence of stands, and forest response to disturbance as a ''natural'' experiment. bugmann ( ) tested model predictions of species composition, biomass, and distribution on a range of sites in the european alps. we assess linknz similarly by comparing output with general characteristics of forest vegetation at sites throughout new zealand. these sites are located across both temperature and precipitation gradients in habitats varying from diverse-species warm-temperate forests to limited-floristic cool-temperate forests (table ) . pacala et al. ( ) tested their spatially explicit model against data from a short chronosequence (up to yr), and against a long-term succession, by comparing species composition and basal area. we compare our model through time against studies of forest successional development on landslides in southwestern new zealand (mark et al. , stewart ). comparisons of models and methods can give confidence if underlying methods are independent (rastetter ) . we compare simulated long-term dynamics against successional sequences deduced by methods based on empirical data and models unrelated to linknz (e.g., ogden , wardle , burns and smale . bugmann et al. ( ) compare versions of forest gap models showing changes due to additional features. we briefly compare results between our model and a test of an allometry- finally, we present and discuss model results for forests where large-scale disturbance appears to play a role in shaping forest structure. the model reproduces the broad patterns of forest succession and composition at a variety of test sites. at riverhead, auckland, a silty clay loam soil texture (field moisture capacity . cm, wilting point of cm) was chosen to represent moister, valley soil conditions. from the simulations, mean relative stem densities at -yr intervals for the main species (with mean biomass Ͼ . mg·ha Ϫ ·yr Ϫ ) were clustered using a group-average linkage with a gamma similarity coefficient (systat ) . this gave three groups of species at the . similarity level. the early-arriving species (group ) separated at the . similarity level into primarily short-lived, small trees (group a) and longer lived tall trees (group b). initially, modeled primary succession proceeds through the fast-growing group a species, especially leptospermum scoparium and kunzea ericoides, with aristotelia serrata also present for the first yr (fig. ) . included in group a is the slow-growing phyllocladus trichomanoides, which can maintain a longer presence. the relative density of these pioneer species drops rapidly after - yr, returning only when large canopy gaps occur after year . the massive conifer agathis australis attains dominance in Ͼ % of the simulated plots by year and, like the group a pioneers, begins at a high density. over the first ϳ yr, agathis also replaces group b, early-establishing hardwood species including weinmannia silvicola, knightia excelsa, elaeocarpus dentatus, and the beech nothofagus truncata (fig. ) . the model suggests, however, that agathis does not regen-erate well in situ, with its relative density declining steadily for Ͼ yr and its biomass dropping until it disappears after - yr. as agathis declines after - yr, the forest becomes co-dominated by species from groups b and , forming an agathis/ hardwood community with an increasing podocarp component (figs. and a) . the group species, beilschmiedia tawa and b. tarairi, rise in numbers, reaching % of total biomass between years and , and then decline to hold a near-constant % of total biomass after yr, as the longer lived group podocarps emerge. of these, dacrydium cupressinum gains slowly in relative density and biomass after group a species disappear, while prumnopitys ferruginea and p. taxifolia increase rapidly as agathis wanes. in the absence of a large disturbance, such as fire, these podocarp species (with a small hardwood component) are predicted to eventually characterize the forest. our simulations indicate that, at this warm new zealand site, maximum forest biomass is reached between and yr, while agathis dominates. during that period, the model predicts a mean basal area of m / ha (fig. b) , of which agathis contributes m /ha. this compares well with a mean basal area of m / ha for agathis, observed in mature (mean age yr) stands . with a drier soil (moisture capacity . cm, wilting point . cm), depicting ridge conditions at riverhead, agathis is predicted to persist at the expense of the group hardwoods. the simulation (not graphed) produces a . % higher mean agathis biomass, with a lower maximum and a smoother decline. the hardwood species beilschmiedia tawa and b. tarairi, which favor more fertile soils and are less tolerant of water stress than agathis, drop in mean biomass by Ͼ %, from . % to . %. in comparison, the three major podocarp species retain - % of total biomass. the droughttolerant prumnopitys taxifolia prospers at the expense of both d. cupressinum and p. ferruginea. in the cooler climate further to the south, near taupo generalized forest gap model fig. . relative stem densities of key species on modeled plots using climate and soil data from riverhead, auckland. other species of lesser importance on the modeled plots include: elaeocarpus hookerianus in group b, quintinia serrata in group , and podocarpus totara and podocarpus hallii in group . in this and all subsequent simulations, the values shown are the means from simulated / ha plots. minimum and maximum mean percentages of total stems are given for each species. ( fig. a) , modeled primary succession on silty clay loam soil proceeds again through kunzea ericoides with leptospermum scoparium, and aristotelia serrata. weinmannia silvicola is replaced by the cooler climate species w. racemosa, and warmer temperate species such as the hardwood beilschmiedia tarairi and the dominant conifer agathis fail to establish. the common north island hardwood b. tawa retains a small, constant biomass (ϳ %) throughout the simulation period. in the first yr, modeled plots are dominated by weinmannia racemosa, k. ericoides, and elaeocarpus species. these species make up Ͼ % of total biomass at year , reduce to % by year as the podocarps dacrydium cupressinum, prumnopitys ferruginea, and p. taxifolia increase, and become a minor component at % by year . modeled community composition is similar to that at lakeside sites in the taupo area (wardle , clarkson and nicholls ) . the successional patterns resemble a sequence described by wardle ( ) for parts of this central north island volcanic plateau area with a deep tephra soil, characterized by d. cupressinum-dominated mixed-podocarp forest establishing by - yr and developing by - yr into a large, mature podocarp-broadleaved forest. by contrast, simulations carried out using the cooler climate conditions for reefton (typical of the south island west coast of new zealand) suggest that the emergent podocarp dacrydium cupressinum, in association with the common hardwood weinmannia racemosa, will more quickly dominate plots in this area (after the initial establishment of aristotelia serrata, leptospermum scoparium, and kunzea ericoides). the model shows prumnopitys and podocarpus species, followed by nothofagus species, beginning to establish after ϳ yr (fig. b) species. apart from n. fusca (to be discussed), forest composition agrees with descriptions of the area (wardle ). the drop-off in biomass over yr at about year represents mortality of the last of the original cohort of the long-lived, dominant d. cupressinum. the gap model predicts that the eventual ''steady-state'' forest composition of the major species at taupo and reefton may be similar (fig. a, b) , with comparable patterns for w. racemosa and the podocarp species d. cupressinum, p. ferruginea, and p. taxifolia at both sites. slight differences are evident, with reefton predicted to have a larger beech component and b. tawa restricted to taupo, as observed in nature. the model generates a similar forest km south at franz josef (fig. c) , where the mean annual temperature is only slightly lower than in reefton (table ) . early succession at this site is started by leptospermum scoparium and aristotelia serrata, rather than kunzea, as at the more northern sites. a similar amount of nothofagus menziesii is predicted in forest at franz josef, as for reefton (fig. b, c) . however, franz josef is located within the -km stretch of the south island west coast where nothofagus is absent (referred to as the ''beech gap''). excluding beech species from the model at franz josef does not alter the forest dynamics greatly, and correctly predicts a dacrydium cupressinum-dominated podocarp forest (fig. d ). other species include weinmannia racemosa, quintinia acutifolia, pseudowintera colorata, and cyathea smithii. still omitting beech species from the model, we simulated climate conditions several hundred meters upslope of the franz josef meteorological station by reducing mean monthly temperatures by Њc. at this upslope site, a mixed hardwood-podocarp forest is sim-ulated with metrosideros umbellata, weinmannia racemosa, podocarpus hallii, and phyllocladus aspleniifolius var. alpinus (fig. e ). other species present include griselinia littoralis, libocedrus bidwillii, and pseudowintera colorata. this change in species composition with elevation corresponds with that commonly observed along the western slopes of the southern alps in new zealand (e.g., wardle ) . the total biomass in these simulated slope forests is about two-thirds that estimated for the lowland podocarp forests. this reduction is caused partly by a change in species composition from the large, lowland podocarp, dacrydium cupressinum, to the smaller-statured podocarp, p. hallii, with the broad-leaved hardwood w. racemosa, and is exacerbated by the decline in biomass of the dominant m. umbellata. metrosideros initially dominates the forest, reaching ϳ mg/ha after yr, but is gradually replaced by podocarpus hallii after yr. on the drier east side of the southern alps, the model simulates very different forests from those on the wetter west side (fig. f, g) . at the driest site (mean precipitation mm/yr) near twizel, on a sandy soil, the model generates a forest dominated by podocarpus hallii, with a small amount of nothofagus solandri var. cliffortioides, phyllocladus aspleniifolius var. alpinus, and prumnopitys taxifolia. early succession at this site is dominated by leptospermum scoparium and n. solandri var. cliffortioides. the simulated biomass of these plots is ϳ mg/ha. although there is no forest at present around twizel, on adjacent slopes there is abundant charcoal evidence for a p. hallii forest before the arrival of polynesian settlers in new zealand (molloy et al. , wells ). on drier, cooler sites, pollen and charcoal evidence from the foot of the ben ohau range near twizel record a p. alpinus-dominated scrub with a lesser p. hallii component and traces of n. solandri var. cliffortioides (mcglone and moar ). at the higher elevation craigieburn site (fig. g) , on a sandy-loam soil, the model generates a mixed nothofagus solandri var. cliffortioides-n. menziesii forest where there is presently solely n. solandri var. cliffortioides. this modeled forest exhibits interesting dynamic behavior, and will be discussed in more detail (see natural monocultures). simulated forest succession at lake thompson (using climate data from the west arm, manapouri station) allowed comparison with several detailed studies of succession in the area (mark et al. , stewart . qualitatively, much of the early pattern of succession observed by mark et al. ( mark et al. ( , was reproduced by linknz, with aristotelia serrata and tually n. menziesii. other species that occur in forested sites close to lake thompson (stewart ), such as pseudowintera colorata, a valley floor forest co-dominant in the understory, and the conifers podocarpus hallii and prumnopitys ferruginea, are also present in our simulations (fig. a, b) . quantitative predictions were more variable. the linknz model reproduced the dynamics of the short-lived pioneer aristotelia serrata, a co-dominant in the -yr-old slip-face plot (exceeding % relative density), and absent from stands Ն yr old (mark et al. ). the principal seral species, leptospermum scoparium, was prolific in the -yr-old stand ( % relative density), much less abundant in the - yr old stands ( %), and not recorded in the mature forest. our simulation reproduced the initial relative density and persistence of l. scoparium, but predicted only % relative density after yr. predictions for the lightdemanding beech species nothofagus solandri var. cliffortioides at year and year were within % and %, respectively of the field observations. the model properly predicted that the mature-forest dominant n. menziesii would establish at an early stage, but gave it only slight increases in relative density until year , whereas mark et al. ( ) found that it occurred in moderate amounts on both -yr-old and -yr-old slip-face plots. the linknz model predicted that high numbers of podocarpus hallii and prumnopitys ferruginea would occur after year . these affect predicted relative densities of other species. weinmannia racemosa was found by mark et al. ( ) to contribute % relative density at year and % in the mature forest. the linknz model predicted % w. racemosa relative density at year , dropping to % at year as the podocarps became abundant (fig. a) . mark et al. ( ) recorded a relatively high density of the hardwood metrosideros umbellata after yr, whereas the model predicted just % for this species after yr. despite these differences, the simulation of an adjacent mature nothofagus menziesii-weinmannia racemosa-pseudowintera colorata forest is still very acceptable (e.g., stewart , mark et al. ). with reference to species' relative densities, we note that our modeled results are the average of stands; individual stands can follow quite distinct trajectories from the mean. introducing relatively infrequent stochastic disturbance ( / ha total plot blow-down on the average of - yr) results in simulated forests with a greater representation of early successional species and lower biomass than in forests where only individual tree gap replacement dynamics are allowed. this regime has the effect of not only increasing the number of gaps over time, but also dramatically altering the stand structure. over time, a plot generally carries several trees so that, when one dies, any remaining individuals are free to respond, but under the blow-down scenario, all remaining trees on the plot are killed (e.g., fig. a vs. fig. a, and fig. b vs. fig. b ). in these simulations, the long-lived podocarp species decline in absolute as well as relative importance, while other species tend to maintain absolute biomass and increase in relative representation. this is illustrated at the reefton site, which has a history of mass disturbances including two major earthquakes in the area during this century (wardle ) . when we imposed a mean disturbance return time of yr and allowed fallen material to remain on site, predicted total biomass of nothofagus species at reefton increased from . % without disturbance to . %. the beech n. fusca is common in the area (wardle ) , but in simulations without disturbance, it was virtually absent (fig. b) . the introduction of disturbance allowed n. fusca to capture Ͼ % of total biomass, increased n. menziesii from % to % of total biomass, and led to the establishment of a small amount of n. solandri. with this disturbance regime, the earlyestablishing and common hardwood weinmannia racemosa retained a constant presence and more than doubled its share of biomass from . % to . %. these gains came at the expense of the podocarps, with the biomass of prumnopitys species reduced by onehalf and dacrydium cupressinum reduced by one-third to %, compared to a scenario without random disturbance. the lists of species and successional patterns generated by the model for different sites in new zealand agree closely with those observed at the local sites (e.g., wardle , wardle ). at the sites tested, the model does not establish any species where it does not belong, with the exception of the ''beech gap,'' to be discussed. for example, the commonly described pattern of colonization, which has the fast-colonizing kunzea ericoides and leptospermum scoparium acting as ''nurse'' species for agathis australis or podocarps (ogden ) , is reproduced in the riverhead, auckland simulation ( fig. a) , as is the eventual replacement of agathis by hardwoods and podocarps . in the initial - yr, the riverhead simulation also shows the common hardwoods weinmannia silvicola, knightia excelsa, elaeocarpus dentatus, the beech nothofagus truncata, and phyllocladus trichomanoides establishing in numbers, and then gradually being overtopped and replaced by agathis (fig. ) . this successional sequence in these warmer temperate forests is described by ecroyd ( ) and burns and smale ( ) . the model also reproduces observed changes in species composition for different soils. dri-er soil sites favor longer term agathis occupation, whereas moister soils suit hardwood species (ecroyd ) . the biomass and basal area estimates produced by the model are more difficult to evaluate, but agree in general with published estimates. from a harvesting trial in a typical -yr-old agathis stand in the hunua ranges south of auckland, madgwick et al. ( ) estimated the agathis biomass component at ϳ mg/ ha. on agathis-occupied plots, with hunua climate data, the model predicts a mean ϳ mg/ha agathis component at yr. huge biomass is possible in clumped stands of mature agathis forest (wardle ) . hinds and reid ( ) estimate that a representative area of a typical mature agathis forest with merchantable stems/ha could produce Ͼ mg/ha, on average, of commercial timber. madgwick et al. ( ) found that stemwood made up % of total agathis biomass in their study; this factor generates an approximate total biomass estimate of mg/ha. this compares with the model estimate in which total agathis biomass reaches a peak of mg/ha in - yr old stands. near riverhead, ogden ( ) recorded basal areas of agathis of m /ha for a ϳ -yr-old stand and m /ha for a young ϳ -yr-old ''ricker'' stand. in comparison, our model simulations predict lower mean basal areas of m /ha on -yr-old agathis-dominated stands and m /ha at yr (fig. b ). burns and smale ( ) , on an intermediate-stage -yr-old site on the coromandel peninsula, obtained a total basal area of m /ha, of which % was contributed by agathis. our model, with their coromandel site climate data, predicted a similar total stand basal area, but with an % agathis component. for reefton, we estimated undisturbed mature podocarp-beech forest aboveground biomass at ϳ mg/ ha (fig. b) and belowground biomass at ϳ mg/ ha. for periodically disturbed mature podocarp-beech forest, above-and belowground biomass was ϳ and ϳ mg/ha, respectively. beets ( ) recorded aboveground (living) and belowground (excluding logs) biomass values of mg/ha and mg/ha, which included mg/ha of roots, at a mature mixedpodocarp-beech site near reefton. in the craigieburn range, several studies have investigated nothofagus solandri var. cliffortioides aboveground biomass, finding values that range between and mg/ha (benecke and nordmeyer , schoenenberger , harcombe et al. ). our simulated values range from to mg/ha. although the model successfully simulates broad successional patterns within new zealand forests, detailed patterns may not be exactly reproduced, particularly during the early-establishment stages. forest gap models incorporate stochastic elements to mimic many ecosystem processes and produce multiple simulations to obtain average results and calculate confidence limits. uncertainty in model data and possible errors in ecological applications vol. , no. field data also obscure reconstructions of past events (rastetter ) . deviations between model and reality result from a number of sources. these include potential errors in site parameters such as climate or soil water-holding capacity, errors in species parameters, and flaws in our understanding (and in modeling this understanding) of how site and species characteristics interact and affect forest growth. the results from lake thompson are instructive. our climate estimates for lake thompson are taken from a site km distant, in an area of high relief and climatic extremes; our estimate of initial site fertility may also be imprecise. we use the same set of growth parameters for each species throughout new zealand (ignoring ecotypic variation) and some of these parameters are relatively imprecise estimates. a chronic problem with testing gap models in this way is that the species potentially available on a plot exceed those that naturally occur (the model provides for an omnipresent seed source, ignoring seed dispersal mechanisms and differing arrival times). this results in a relatively high percentage of ''other'' species that may exist for only several years before dying off. in addition, during early establishment, the model initiates all individuals as equal-aged saplings with a mean stem dbh of . cm. time required to reach this point is not explicitly accounted for and there can already be considerable age differences between individuals, depending upon their species' growth characteristics. despite these problems, the detailed pattern of succession simulated for landslides near lake thompson is reasonable. the species characteristics given to linknz were not altered nor were the species limited to those present in the lake thompson area. develice ( ) presented a basic foret-type model with allometric parameters set for the five tree species of greatest importance at the lake thompson landslides. even so, his model overestimated the initial density of nothofagus solandri var. cliffortioides and the subsequent density of n. menziesii. in these develice ( ) simulations, n. menziesii accounted for nearly % of total stand density by year , whereas mark et al. ( mark et al. ( , found that its density was generally Ͻ % of the total. the linknz model produced a better approximation to field counts of these nothofagus species, and predicted the increases in pseudowintera colorata over time that were noted by mark et al. ( ) . it did deviate from field observations by initially establishing podocarp species (not included by develice ); although these species did not become a significant part of the site biomass until year (fig. b) , they lowered relative density predictions for the hardwood species. the simulated early and numerous establishment of these bird-dispersed podocarp species lends support to the contention of mark et al. ( ) that the initial floristics model of primary succession (egler ) , in which species arrive simultaneously and successively gain dominance according to their life history attributes, may not fully account for the early dynamics on these slip faces. in summary, although our results and those of develice ( ) deviate in some details from the short-term pattern of succession reported by mark and co-workers, the mature forest simulation of linknz corresponded closely to that described by stewart ( ) and mark et al. ( ) . having established the validity of the model for reproducing general successional patterns across a range of sites in new zealand, we then used the model to provide some insights on several ongoing debates concerning ecological patterns and processes in new zealand. there has been debate concerning the ''lack'' of regeneration in agathis australis forests (for discussion, see ecroyd and ogden ) . our results, based solely on gap-phase replacement dynamics inherent in the model, support the primary succession theory of egler ( ) and the early belief (cockayne ) that agathis is successional to a climax podocarp forest (figs. , a) and that strongly agathis-dominated forests would occur only in the first yr after largescale disturbance. the gap size and frequencies produced by the model are a consequence of the comparative life history attributes set for the trees that occupy the site. thus, long-lived trees will produce gaps only infrequently; in the case of agathis, this frequency is so low that there is sufficient time for the shade-tolerant hardwoods and podocarps to become well established, reducing the likelihood that enough light would penetrate through the understory of a tree-sized gap to permit abundant agathis regeneration. in a study of agathis treefall gaps, ogden et al. ( ) found that agathis established in only a few, enough to maintain a presence but not dominance. they estimated that, owing to its longevity (mean Ͼ yr), agathis could survive on any site up to - yr. the corresponding simulation ( fig. a) , without large-scale disturbance, shows agathis declining from an initial dominance, but remaining a significant component of the forest for nearly yr. many workers have pointed out the importance of larger scale, infrequent disturbance to new zealand forest dynamics (e.g., stewart , ogden ) , and have urged acceptance of ''kinetic'' models (e.g., veblen et al. ) in which stochastic disturbance is accepted as a selective force. ahmed and ogden ( ) inferred from their study of agathis population structure that episodic regeneration occurred at intervals of - yr. our introduction of stochastic disturbance of this frequency into the dynamics of the model (fig. a) have gone, declining to zero by year (fig. a) . in the stochastically disturbed scenario (fig. a) , agathis biomass remains at ϳ % of total biomass over the entire interval between and yr. our results are consistent with the conclusion of ahmed and ogden ( ) : agathis is a successional species that maintains a strong presence in the forests of northland because of repeated disturbance. nothofagus species are completely absent from a -km stretch along the central west coast of the south island, and are also absent from stewart island, km south of the south island. cockayne ( ) suggested that this absence could be the result of insufficient time for beech to have recolonized the area since the end of the last glaciation (ϳ yr bp). our results for sites within the ''beech gap,'' such as franz josef and hokitika (data not shown), lend support to cockayne's hypothesis. when beech is part of the available species pool, it can establish and become a permanent, if lowbiomass, component of the forest. even when beech availability on the site was delayed yr to allow the forest to fully establish first, linknz indicated that a small amount of beech could establish. this suggests that poor modes of dispersal in beech may play a more significant role than any total inability to compete. wardle ( ) also suggests that new zealand beech may compete less effectively with existing vegetation where the rainfall is high, such as on the west coast, than in the drier conditions to the east of the axial ranges. the linknz model supports this contention, because the simulations show that beech requires a longer period of time to become established in the ''beech gap'' sites than on the drier, cooler east side of the south island in the craigieburn range (compare fig. b , c with fig. f, g) . beech establishment in this region may also be influenced by the effects of stand-level disturbance on soil fertility. the model suggests that stochastic disturbances that create gaps larger than normal treefall size promote the establishment of some beech species. wardle ( ) points out that beech can be outcompeted in low-elevation, high-rainfall areas owing to difficulties in finding suitable sites and increasing competition in the high-density, species-rich understories. ogden ( ) describes the role of synchronized cohort mortality in the dynamics of beech and how disturbance promotes nothofagus fusca establishment. when we included beech in the species pool and introduced wind-blow disturbances ( -yr mean return time) to the simulations at franz josef located in the ''beech gap,'' beech biomass increased by a factor of to reach ϳ % of the total; n. menziesii biomass doubled, and the fast-growing n. fusca established and attained Ͼ % of total biomass. by contrast, a disturbance regime that removed organic matter from the site inhibited beech species establishment and produced a more typical low-elevation hardwood-podocarp forest. ogden ( ) notes that n. fusca prefers higher fertility sites and would be expected to have difficulty establishing. at this low-elevation, low-fertility site, the model predicts that other species, such as the common hardwood weinmannia racemosa, would capture the area and lead to the establishment of large, dominant podocarps such as dacrydium cupressinum. our results for the craigieburn forest show that biomass contributions of the beech species nothofagus solandri var. cliffortioides and n. menziesii tend to oscillate out of phase with one another in a damped cycle of ϳ yr (fig. a ). an ecological interpretation of this behavior is that, as the fast-growing, light-demanding, even-aged stands of n. solandri var. cliffortioides thin, they become replaced by relatively evenaged stands of the shade-tolerant n. menziesii. when these n. menziesii stands senesce, the faster growing n. solandri var. cliffortioides begin to recapture the site. because n. menziesii is longer lived and can continue to regenerate under its own canopy, these oscillations lengthen and decrease in amplitude over subsequent generations. this ''counter-cyclical succession'' is a consequence of the life history attributes of the two species most suited to the cool craigieburn climate. both species have wide, overlapping soil fertility, soil moisture, and climatic tolerances (wardle , benecke and allen ; g. m. j. hall and d. y. hollinger, unpublished manuscript) . in new zealand, these species form almost continuous alpine and subalpine forests throughout the axial mountain ranges of both main islands. wardle ( ) found that in mixed stands, dense, smalldiameter (young) nothofagus menziesii usually occur in conjunction with large-diameter (old) n. solandri var. cliffortioides and, conversely, stands with low numbers of large n. menziesii trees often have high densities of young n. solandri var. cliffortioides trees. ogden ( ) further suggested that n. solandri var. cliffortioides will gradually be replaced by n. menziesii unless the stand is severely disturbed. in fact, the craigieburn forests are essentially monocultures of n. solandri var. cliffortioides, with few other canopy species. disturbance events such as wind, earthquake-triggered landslips, and heavy snowfall (wardle ) frequently disrupt these subalpine and alpine forests on the eastern slopes of the south island axial range. age-diameter distributions indicate that stands may be severely damaged by gales at periods of ϳ - yr, and stands suffer minor damage at intervals of - yr (wardle , jane , harcombe et al. ). when we investigated the influence of disturbance on the dynamics and biomass of n. solandri var. cliffortioides-n. menziesii forests by adding stochastic disturbance (blowdown of whole-plot biomass) to the dynamics of the model, the counter-cyclical pattern of succession was removed (fig. b) . furthermore, as the mean interval between disturbances decreased, the relative percentage and absolute amount of n. menziesii in the resulting stands decreased from a % dominance to Ͻ % for mean intervals greater than one event every yr (fig. ) . this model behavior provides support for wardle's ( ) conclusion that stability favors n. menziesii and disturbance favors n. solandri var. cliffortioides, and suggests why n. solandri var. cliffortioides can be so dominant in disturbance-prone subalpine forests. we evaluated the degree to which principles and relationships derived from north american studies could be used to simulate the structure and dynamics of new zealand forest ecosystems. the characteristics of new zealand tree species are significantly different from those of eastern north american trees. new zealand species are generally long-lived evergreens with low n and high specific mass foliage that is retained in the canopy for several years. yet, a model that was based on ecological processes of tree competition and growth, litter decomposition, and n cycling that originated primarily in north america and was designed to simulate the ecology of eastern north american species, only required minor modifications to acceptably simulate general forest patterns and processes across climatic gradients in a range of new zealand forest types. the most significant modifications improved the way in which the predecessor model, linkages, calculated the forest floor light environment and modified the slow growth rate conditions that trigger mortality. overall, our results tested the adequacy of the ecological processes embodied in forest simulators such as linkages. they provided support for the model's underlying hypothesis: interactions among demographic processes determining plant population structure, microbial processes determining n availability, and geological processes determining water availability explain much of the observed variation in ecosystem c and n storage and cycling (pastor and post ) . in this framework, geology and climate act as constraints within which feedbacks between vegetation and light availability, and between vegetation and n availability, operate. by incorporating a simple disturbance regime into the model, we also supported the hypothesis that large-scale disturbance is of importance in shaping the dynamics and current composition of new zealand forests (veblen and stewart , ogden , wardle ). the linknz model is a versatile simulation model of vegetation patterns and processes in new zealand forests. it may find additional practical applications in investigating the impacts of climatic change, forest harvesting practices, forest restoration, or introduced animal impacts on the dynamics of indigenous vegetation. furthermore, the modifications that we have incorporated should also improve the performance of the model in its original domain, the northeastern united states. acknowledgments many colleagues at landcare research and at the department of conservation provided assistance with this project. predicting the effects of different harvesting regimes on productivity and yield in northern hardwoods predicting the effects of rotation length, harvest intensity, and fertilization on fiber yield from northern hardwood forests in new england population dynamics of the emergent conifer agathis australis (d.don) lindl. (kauri) in new zealand. . population structures and tree growth rates in mature stands forest recovery after logging in lowland dense rimu forest, westland, new zealand amount and distribution of dry matter in a mature beech/podocarp community new zealand's mountain forests: their use and abuse. pages - in yang yupo and zhang jiangling, editors. protection and management of mountain forests. iufro project group p . - : ecology of subalpine zones growth and water use in nothofagus truncata (hard beech) in temperate hill country carbon uptake and allocation by nothofagus solandri var. cliffortioides (hook. f.) poole and pinus contorta douglas ex loudon ssp. contorta at montane and subalpine altitudes some ecological consequences of a computer model of forest growth forest response to climatic change: effects of parameter estimation and choice of weather patterns on the reliability of projections gap phase replacement in a maple-basswood forest a simplified forest model to study species composition along climate gradients a comparison of forest gap models structure and behavior changes in structure and composition over fifteen years in a secondary kauri (agathis australis)-tanekaha (phyllocladus trichomanoides) forest stand the distribution of beech (nothofagus) species in the east taupo zone after the bp volcanic eruptions monograph on the new zealand beech forests. part . the ecology of the forests and the taxonomy of the beeches the vegetation of new zealand the vegetation of wisconsin. an ordination of plant communities preliminary account of litter production in a new zealand lowland podocarp-rata-broadleaf forest test of a forest dynamics simulator in new zealand biological flora of new zealand. . agathis australis (d. don) lindl. (araucariaceae). kauri vegetation science concepts. i. initial floristic composition, a factor in old-field vegetation development patches and structural components for a landscape ecology pc-recce vegetation inventory data analysis spatial and temporal patterns in structure, biomass, growth, and mortality in a monospecific nothofagus solandri var. cliffortioides forest in new zealand forest trees and timbers of new zealand carbon dioxide exchange between an undisturbed old-growth temperate forest and the atmosphere wind damage as an ecological process in mountain beech forests of canterbury preliminary notes on seeding and seedlings in red and hard beech forests of north westland and the silvicultural implications description and simulation of tree-layer composition and size distributions in a primaeval picea-pinus forest above-ground biomass, nutrients, and energy content of trees in a second-growth stand of agathis australis forest succession on landslides in the fiord ecological region, southwestern new zealand forest succession on landslides above lake thompson, fiordland exe: a climatically sensitive model to study climate change and co enrichment effects on forests dryland holocene vegetation history distribution of subfossil forest remains, eastern south island soils in the new zealand landscape. mallinson rendel, in association with the new zealand society of soil science Ü ber den lichtfaktor in den pflanzengesellschaften und seine bedeutung fü r die stoffproduktion meteorological observations community matrix model predictions of future forest composition at russell state forest an introduction to plant demography with special reference to new zealand trees forest dynamics and stand-level dieback in new zealand's nothofagus forests ecology of new zealand nothofagus forests population dynamics of the emergent conifer agathis australis (d. don) lindl. (kauri) in new zealand. ii. seedling population sizes and gap-phase regeneration forest models defined by field measurements: i. the design of a northeastern forest simulator calculating thornthwaite's and mather's aet using an approximating function development of a linked forest productivity-soil process model. oak ridge national laboratory ornl/tm- response of northern forests to co -induced climate change linkages: an individualbased forest ecosystem model a simulation model for the transient effects of climate change on forest landscapes validating models of ecosystem response to global change above ground biomass of mountain beech (nothofagus solandri (hook.f) oerst. var. cliffortioides (hook.f.) poole) in different stands near timber a theory of forest dynamics a review of forest patch models and their application to global change research development of an appalachian forest succession model and its application to assessment of the impact of the chestnut blight transient responses of forests to co -induced climatic change: simulation modelling experiments in eastern north america simulating the role of climate change and species immigration on forest succession forest dynamics and disturbance in a beech/hardwood forest the significance of life history strategies in the developmental history of mixed beech (nothofagus) forests systat manual, version . . spss, chicago structure and dynamics of old growth nothofagus forests in the valdivian andes on the conifer regeneration gap in new zealand: the dynamics of libocedrus bidwillii stands on south island the new zealand beeches: ecology, utilisation and management facets of the distribution of forest vegetation in new zealand vegetation of new zealand pattern and process in the plant community ecology of podocarpus hallii in central otago geomorphology of the central southern alps, new zealand: the interaction of plate collision and atmospheric circulation the hubbard brook ecosystem study: forest biomass and production the gap theory in forest dynamics. the botanical magazine in particular, larry burrows, glenn stewart, robert allen, ian payton, and bruce burns assisted with comments about the sites and forest ecosystems. matt mcglone, glenn stewart, and two unnamed referees kindly reviewed the manuscript and suggested improvements. this project was funded by the foundation for research, science and technology under contract number c . a list of the new zealand forest species selected for input to the linknz forest gap model is available in esa's electronic data archive: ecological archives a - . key: cord- -qfquedya authors: ruthberg, jeremy s.; quereshy, humzah a.; jella, tarun; kocharyan, armine; d'anza, brian; maronian, nicole; otteson, todd d. title: geospatial analysis of covid- and otolaryngologists above age () date: - - journal: am j otolaryngol doi: . /j.amjoto. . sha: doc_id: cord_uid: qfquedya objective: the novel coronavirus (covid- ) is disproportionately impacting older individuals and healthcare workers. otolaryngologists are especially susceptible with the elevated risk of aerosolization and corresponding high viral loads. this study utilizes a geospatial analysis to illustrate the comparative risks of older otolaryngologists across the united states during the covid- pandemic. methods and materials: demographic and state population data were extracted from the state physician workforce reports published by the aamc for the year . a geospatial heat map of the united states was then constructed to illustrate the location of covid- confirmed case counts and the distributions of ents over years for each state. results: in , out of a total of practicing u.s. ent surgeons, were older than years ( . %). the states with the highest proportion of ents over were maine, delaware, hawaii, and louisiana. the states with the highest ratios of confirmed covid- cases to the number of total ents over were new york, new jersey, massachusetts, and michigan. conclusions: based on our models, new york, new jersey, massachusetts, and michigan represent states where older ents may be the most susceptible to developing severe complications from nosocomial transmission of covid- due to a combination of high covid- case volumes and a high proportion of ents over years. the novel coronavirus (covid- ) is a global pandemic that has rapidly spread across the world. although the virus infects individuals of all ages, epidemiological reports demonstrate that older age is a significant contributing factor for symptomatic presentation, severe disease course, and death [ ] . this is illustrated by the significant increase in case fatality rates (cfr) with age. in china, the cfr of the general populace is . % with rates skyrocketing to . % and . % in patients - and over , respectively [ ] . in italy, reports of case fatality are even higher, with . % in individuals - years, . % in individuals - years, and . % in individuals over years [ ] . in addition to age, nosocomial exposure also serves as a significant risk factor, rendering health care workers particularly susceptible. early data from wuhan, china reported that nearly % of covid- infections in a single hospital system were comprised of health care workers [ ] . the novel coronavirus' dramatic impact on medical personnel parallels the epidemiology of the severe acute respiratory disease (sars) outbreak in which % of global cases were health care worker infections [ ] . covid- colonizes the upper respiratory mucosa with a high viral load, whether a patient is symptomatic or asymptomatic [ ] . as covid- demonstrates the potential for both respiratory and aerosol transmission, otolaryngologists (ents) are at an elevated risk working in close proximity to the upper respiratory tract within the head and neck region [ , ] . due to the vast diversity in diagnostic and operative procedures performed on the upper airway within ent, there is a high risk of aerosolization, leading to the potential for transmission of high viral loads to the provider [ ] . the director of an intensive care unit in wuhan, china commented that journal pre-proof j o u r n a l p r e -p r o o f otolaryngologists and ophthalmologists were infected at higher rates when compared to other doctors in the same hospitals, and the same trends are reported in europe [ ] . in response, an international collaboration amongst thirteen institutions has put forth recommendations to ensure the safety of the otolaryngology community throughout the course of this pandemic [ ]. protecting vulnerable members of the work force during these unprecedented times is of the utmost importance. the present study compares the geospatial distribution of covid- confirmed cases against the distribution of ents over the age of to highlight the potential risks to this segment of vulnerable health care providers. were older than years ( . %). the states with the highest proportion of ents over years were documented along with the total number of ents for that state (table ) . the proportion of ents over age ranged from . % in kansas to . % in maine (appendix). ratios representing the total state population divided by the number of total ents for that state were also documented ( table ) . of the states with the highest proportion of ents over years, state populations per ent provider ranged from , to , (table ) . a heat map illustrating the u.s. states with the highest proportion of ents over and the current geographic covid- case volume was depicted in figure . covid- case volume was accurate as of april th , . the highest risk states for older ents, defined by the ratio of total confirmed covid- case volume to the total number of ent providers over , were new york, new jersey, massachusetts, and michigan, among others ( table ). the highest number of confirmed covid- cases per ent over years old was new york ( ) and the lowest was hawaii ( ). data for vermont, north dakota, south dakota, wyoming, and alaska were not incorporated into the heat map as there were fewer than ent providers over in each of these states, which was the aamc's cut-off for publishing a given state's data. no statistically significant differences were found in the average proportion of ents over by u.s. census region (figure ) . the average percentages within the midwest, northeast, south, and west were . %, . %, . %, and . %, respectively (p= . ). additional demographic data for u.s. otolaryngologists and covid- case counts for all states is documented in the appendix. cases have been relatively low in these states. therefore, ent providers in these states may not be experiencing the same extent of viral exposure within healthcare settings as providers serving in new york, new jersey, massachusetts, and michigan, which currently have the highest ratios of confirmed covid- cases to the number of ent providers over years. these states will likely continue to be vulnerable with anticipated rises in case volumes or in the setting of a covid- re-emergence. rates of nosocomial transmission and the susceptibility of all health care providers during this pandemic is frightening [ ] . however, with careful precautions, it is possible to limit the risk unto health care workers and curb nosocomial transmission. with the proper personal protective equipment and adequate hand hygiene, a cohort of health care workers was able to avoid nosocomial transmission while treating a confirmed covid- patient with pneumonia despite exposure during icu intubation and mechanical ventilation [ ] . various safety recommendations for ents during the covid- pandemic have been proposed to achieve similarly successful outcomes. for otolaryngologists specifically, routine, nonurgent appointments and elective surgeries have largely been postponed [ ] . some have recommended deferring all endoscopies unless deemed necessary to reduce -day morbidity, such as circumstances pertaining to malignancy and airway risk, among others [ ] . for essential urgent and emergent procedures, which must proceed despite the risks, determination of whether to use powered air-purifying respirators (paprs) versus n s should be assessed by each institution as both forms of masks offer distinct advantages and disadvantages [ ] . however, at a minimum, otolaryngologists should don a respirator, gown, cap, eye protection, and gloves [ ] . moreover, studies from the ebola outbreak reported that in some circumstances, up to . % of providers self-contaminated while removing ppe [ ]; therefore, careful consideration must be applied to doffing ppe during the covid- pandemic. even after exercising adequate precautions, it is sensible to recommend that vulnerable demographics limit their exposure to possible covid- infection as much as possible [ ] . as rates of new cases start to decrease, otolaryngologists who are highly susceptible to severe complications from nosocomial transmission should exercise caution in their "return-to-work" planning in the coming weeks. the present study assesses the comparative risk of older otolaryngologists developing severe symptoms from covid- . however, there are many other variables that would need to be factored into this discussion to adequately predict the risks to ents in the united states. first, in addition to age, clinical comorbidities, male sex, and smoking history also play significant roles in the risk of developing severe complications secondary to covid- infection [ ] . furthermore, risk of exposure is also highly dependent on local institutional practices, availability of resources such as personal protective equipment, and the scope of the hospital staff available to assist in the care for covid- patients [ ] , which are not factored into our model. although the provider data from was the most recent data available from the aamc, it may not exactly reflect the current workforce in each state, since there may have been movement or retirements since the data was released in . across the world, countries have reported the disproportionate impact of covid- on older individuals and health care workers. with otolaryngologists at increased susceptibility due to the nature of their work and the type of procedures they perform, protocols must be implemented to protect otolaryngologists, especially those most vulnerable. it is vital that, as the nation starts to recover from the covid- pandemic, we evaluate how best older ents can serve while limiting their risk of exposure. j o u r n a l p r e -p r o o f covid- : risk factors for severe disease and death case-fatality rate and characteristics of patients dying in relation to covid- in italy clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in severe acute respiratory syndrome: what have we learned two years later? can sars-cov- viral load in upper respiratory specimens of infected patients precautions for endoscopic transnasal skull base surgery during the covid- covid- pandemic: effects and evidence-based recommendations for otolaryngology and head and neck surgery practice covid- : protecting our ent workforce europe's doctors repeat errors made in wuhan, china medics say safety recommendations for evaluation and surgery of the head and neck during the covid- pandemic an interactive web-based dashboard to track covid- in real time characteristics of and important lessons from the covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention covid- and the risk to health care workers: a case report covid- and the otolaryngologist -preliminary evidence-based review practical recommendations for critical care and anesthesiology teams caring for novel coronavirus ( -ncov) patients j o u r n a l p r e -p r o o f key: cord- - o z v authors: qu, jiangwen; wickramasinghe, n.chandra title: the world should establish an early warning system for new viral infectious diseases by space‐weather monitoring date: - - journal: medcomm (beijing) doi: . /mco . sha: doc_id: cord_uid: o z v with the emergence of several new epidemics of viral infections – sars, mers, ebola, zika, influenza a (h n ) pandemic,covid‐ ‐ over the past decades we suggest that a world‐wide programme of stratospheric surveillance and space weather monitoring should be urgently put in place without further delay. since the s, new infectious diseases have been emerging all over the planet, with serious repercussions on human health, global politics and the world economy. so far, more than kinds of new infectious diseases have been found in the world, most of which are of viral origin. the occurrence of new viral infectious diseases often has the manifestation of strong contagion, rapid transmission, wide epidemic scope, high mortality. they are often difficult to predict or prevent, and can easily develop into serious public health emergencies causing grave international concern. however, despite all the advances in medical science and molecular biology, the scientific community still lacks sufficient understanding of the causes of the sudden emergence of new viral diseases, including relevant environmental and epidemiological factors that could be at work. at the present time, our ability to detect new pathogens before they lead to epidemic or pandemic disease is still woefully inadequate. to quickly and effectively respond to emerging and unexplained infectious disease outbreaks a well thought-out early-warning technol-ogy system needs to be designed and put in place. the primary goal of such a system should be to guide us to discover new pathogens before they enter the human population. the recent covid- outbreak has confirmed the necessity of establishing such an early warning system. there are a wide range of uncertain factors in the emergence and spread of new infectious diseases that needs to be explored. within the current framework of medical knowledge most researchers think it impossible to predict when and where the next pandemic will occur. if one attempts to make any such prediction one needs to comprehensively detect countless potential pathogens in every possible location including the high atmosphere; but this method requires an extent of manpower and material resources that is not realistic at the present time. the most important prerequisite to early warning is to fully identify and explore those factors that are worth monitoring, and discover methods to detect an incipient epidemic in a local area before it begins to take on disastrous epidemic or pandemic proportions. once a potential pathogen is identified it is important next to determine through gene sequencing techniques (e.g. pcr) the precise species and its variants as quickly as possible. it would then be possible to launch a research program to produce effective preventive vaccines, devise treatment methods or manufacture drugs as may be relevant. if there is a way to make effective predictions of possible outbreaks of infectious diseases ahead of their occurrence we may have enough early warning so that actions to respond to an epidemic can be prompt and timely. with a surge of new viral infectious diseases appearing recently we could ask the following questions: why do these new viral infectious diseases emerge at this particular time? why do they manifest themselves in particular geographical areas? what are the factors that lead to the emergence of these new viral infectious diseases in the first place? how can we predict future new viruses? in order to attempt to answer these questions, we will need to engage in the exchange of information across diverse disciplines and embark on projects that involve inter-disciplinary cooperation. it is becoming amply clear that we cannot solve the most fundamental questions relating to the origin of new viral infectious diseases within the comfort zone of earth-bound medical science alone. first and foremost we need to abandon our tendency towards academic isolation and examine relevant facts from widely disparate fields -physics, meteorology and space science -if we are to achieve our desired objectives. it is only with such an initiative that we can come anywhere near the prevention and control of infectious diseases in the long term. at the present time we tend to believe that the emergence of new viral infectious diseases is mainly related to human activities or ecological factors. these include contact with wild animals, animal trade, new farmland reclamation, urbanization and rapid population growth, international tourism, population flow, climate change and similar factors. however, a stark fact that has either gone unnoticed or ignored is that most new viral infectious diseases seem to emerge in specific years -immediately implying an astronomical context. the inevitable implication is that there must be some "unusual" cosmic factors in these specific years -in the earth's configuration in relation to the wider universe -which play a decisive role. therefore, only by discovering these "unusual" factors can we expect to find the root cause of occurrence of new viral infectious diseases, and thus be able to make scientific predictions of future new pandemics. if particular years can be identified as a causative link an astronomical connection immediately suggests itself. the first lesson from astronomy is of course that the earth is an insignificant planet in the universe -one of perhaps a hundred billion similar planets in our galaxy alone. as humans, we live on planet earth but we also live in a far wider context -within a universe which is full of similar planets. recent studies have shown the likelihood of life on earth being part of a cosmic-wide biosphere. , so it is by no means impossible that viruses which can relate to life on earth may exist on a grand astronomical scale. we also know that the earth is physically connected to the universe -cosmic rays from the sun and from the galaxy reaches the earth and also - of tonnes of meteoric dust (some of it organic) enters the earth every single day. it is a pity that most modern researchers in the biological sciences do not realize these facts. it would appear very likely that all life on the earth, including humans, will be genetically affected by the changes of our immediate space environment and various accompanying cosmic phenomena at any time. these include a variable flux of ionizing radiation -x rays, gamma rays, cosmic rays -that have a mutagenic effect on endemic terrestrial viruses, and even perhaps the addition of viruses from space, a wider cosmic environment, included in the daily tonnage of debris entering our planet from space. our previous studies have pointed out that sunspot extremes or +/- year is an important risk factor for the occurrence of new viral infectious diseases. [ ] [ ] [ ] [ ] [ ] sunspot numbers are related to solar activity. during solar maximum the sun produces high-energy and low-energy solar particles by a process of mass ejections from the sun's surface and solar flares. when the sun is least active, the solar magnetic field gets weaker and there will be more galactic cosmic rays entering the earth. we discussed in an earlier paper that the present time - is characterized by very low sunspot numbers and we are in a solar minimum that is the lowest in over years. ionizing radiation (cosmic rays) which peak at this time can cause virus mutation as well as genetic recombination, particularly if viruses are included in a biosphere extending even beyond the tropopause. in order to verify the correctness of this theory we issued an early warning in a letter to current science published in november . here we explicitly reminded the world that new infective viruses are likely to emerge in the ensuing months from mutations and/or ingress and that public health authorities must be vigilant and take necessary action. the emergence of the covid- outbreak uncannily confirms the accuracy of our early warning and highlights the urgency of taking appropriate precautions for future safety without further prevarication. it is interesting in this context to recall that the word influenza comes from the italian word influencia, meaning influence -and implying in this case influence of the stars. in the middle ages people saw connections between phenomena in the skies and events on earth, and on this basis came to believe that many disasters were indeed related to the stars and celestial phenomena. to ancient f i g u r e an early warning framework diagram based on space-weather monitoring people it seemed rational to believe that stars and the universe could release "things" affecting the earth! in certain respects, they appear to have been right. as the philosopher georg wilhelm friedrich once said, what a nation needs is for people to look up at the stars rather than down on the ground, and in this way a nation can have hope. medical science should perhaps seek the cause of new viral infectious diseases by looking up at the stars. the famous chinese book called "the golden mean" says: "preparedness ensures success, and unpreparedness spells failure." in our view "preparedness" at the present time involves setting up means to detect influences from outside the earth, including conditions of space weather, cosmic ray flux, and arrival of novel cosmic strains of bacteria and viruses in the atmosphere. following the discoveries of novel bacteria in the stratosphere at heights of km [ ] [ ] [ ] and the very recent discovery of bacteria on the exterior of the international space station orbiting at a height of km, the possibility of microbial life entering the earth's surface should be considered seriously. , furthermore, we should be guided by recent researches demonstrating that in the pristine environment of the siera nevada mountains (above the atmospheric boundary layer) there is a downward flux of viruses ranging in number from . × to greater than × m - per day. they also confirmed that the deposition rates for bacteria were even greater, ranging from . × to > × m - per day. to say that all this flux detected at a height of km came from the ground is premature in our view. it is not too late to begin seriously planning for a space-oriented monitoring strategy for detecting new viral/bacterial pathogens before they entered a human pop-ulation. the present crisis relating to the emergence of covid- and its disastrous global spread is serious enough, but our preparation should include the possibility of more lethal pandemics in the future. technologies for monitoring space weather, including cosmic ray flux and stratospheric microbial flux, do certainly exist at the present time. the desire and the will to deploy them for this purpose should be considered a prime responsibility of the nations of the world. failing to do so will be a treachery to our intelligence. we conclude by reiterating that a continual monitoring of the stratosphere for its bacterial and viral content as well as in situ gene sequencing which is well within our biotech and space capabilities should be carried out as a priority and without further delay. in the event of a new virus or a mutated or recombined virus being detected at, say, an altitude of say km, the settling time to ground level to reach the human population could be many months. this would be enough time for mitigation strategies to be put in place. as arthur c. clarke once said the dinosaurs became extinct because they did not have space-guard programme. let us hope that we humans in could be wiser. finally we propose the following framework as a strategy for the future amelioration of pandemic-caused disasters ( figure ): . establishing a cosmic ray monitoring stations including in the troposphere, as high priority. . concurrently setting up virus monitoring stations, with in situ polymerase chain reaction (pcr) equipment, in high altitude locations, preferably including one sited above the atmospheric boundary layer. balloon borne samplers should also be considered, as well global trends in emerging infectious diseases astronomical origins of life: steps towards panspermia lamarck and panspermia -on the efficient spread of living systems throughout the cosmos weakened magnetic field, cosmic rays and the zika virus outbreak is sunspot activity a factor in influenza pandemics mers and the sunspot cycle sunspot activity, influenza and ebola outbreak connection sunspot cycle minima and pandemics: the case for vigilance? space weather and pandemic warnings? detection of living cells in stratospheric samples bacillus aerius sp. nov., bacillus aerophilus sp. nov., bacillus stratosphericus sp. nov. and bacillus altitudinis sp. nov., isolated from cryogenic tubes used for collecting air samples from high altitudes janibacter hoylei sp. nov., bacillus isronensis sp. nov. and bacillus aryabhattai sp. nov., isolated from cryotubes used for collecting air from the upper atmosphere deposition rates of viruses and bacteria above the atmospheric boundary layer the dna of bacteria of the world ocean and the earth in cosmic dust at the international space station on the difficulty of lofting electrically charged submicron dust from the earth's surface to the high ionosphere intercontinental spread of covid- on global wind systems virus (pcr) samplers installed on the exterior of a space station. . in the event of potentially harmful variants of a virus or a new virus being identified by pcr analysis, ground strategies are triggered into action. . ground strategies must include checking resources for monitoring spread of the virus in the human population, providing hospital services (including intensive care if relevant) and in a longer term manufacturing appropriate vaccines, strengthening early symptom surveillance to identify abnormal cases. these authors contributed equally to this work. the authors have declared that no competing interests exist. key: cord- -lli qpjz authors: mcneill, v. faye title: covid- and the air we breathe date: - - journal: acs earth space chem doi: . /acsearthspacechem. c sha: doc_id: cord_uid: lli qpjz nan a s i write this, i am sheltering in place with my family at home in new york city, the current global epicenter of the sars-cov- pandemic. ambulance sirens echo, day and night, through largely empty streets. hospitals are overwhelmed with the crushing load of covid- cases and are suffering from shortages of personal protective equipment (ppe) for care providers. more than americans have died of covid- in the past month, with more than of them in new york city. since mid-march, either by choice or in response to shelter-in-place orders, most americans have been staying home and limiting non-essential travel and industrial and business activity has slowed to a crawl. in a dense urban area like this one, most residents have no access to private outdoor space and rely on public parks for exercise, the mental health boost that comes from a connection with nature, and fresh air. conscientious city dwellers now ponder how to maintain safe social distance while sharing limited outdoor space with others. official recommendations in the united states have converged on ft of distance as the rule of thumb for avoiding the exchange of potentially infective respiratory droplets and aerosols, but these recommendations were devised on the basis of observations made in the s for hospital environments. do they hold for outdoors, in a breeze? during exercise? in some places, the outdoor air that we seek is fresher than before the pandemic. shutdowns have resulted in much lower emissions of pollutants related to travel and commercial activity, but other sources of air pollution have remained stable or even increased. household electricity use has increased dramatically, and consumption patterns have shifted as a result of our new, more intensely domestic lifestyle. these changes in emissions coincide with the seasonal meteorological changes that come with the transition from winter into spring, complicating the identification and interpretation of trends from satellite data and long-term monitoring networks. while air quality in new york city is similar to previous years, los angeles residents are luxuriating in the unusually clear skies that the combination of rainy weather and reduced vehicle traffic has provided. dramatic improvements in visibility have been reported in some areas of india, while in others, agricultural burning and the use of solid fuels for household cooking have kept levels of fine particulate matter high, despite shutdowns. long-term exposure to air pollution is associated with many of the medical conditions that put individuals at high risk for complications related to covid- , including respiratory and cardiovascular conditions and diabetes. analysis of data from italy and the united states has begun to reveal a connection between particulate matter with a diameter of less than . μm (pm . ) exposure and covid- deaths. despite any environmental honeymoon that we may be experiencing as a result of pandemic-related shutdowns, a hangover can be expected as the economy reopens and polluting activities resume. the united states environmental protection agency (u.s. epa) has relaxed enforcement of environmental regulations during the crisis, and it is not clear when these will be restored. other pollution sources may also overshoot pre-pandemic levels. for example, until recently, riding the metropolitan transportation authority (mta) subway system with over million fellow passengers each day was part of the rhythm of new york city life and a hallmark of sustainable city living. commuters with options may be slow to re-adopt public transportation out of fear of exposure to sars-cov- in crowded environments, relying instead on more polluting modes of transportation. on the other hand, mandated work-from-home and global restrictions on business travel have forced a mass technical and cultural adjustment to collaborating and connecting online via videoconference. we may emerge from this crisis with a much higher bar for long distance air travel for meetings. more flexible work-from-home policies, in addition to aiding social distancing in the uncertain mid-term future, could lead to less traffic congestion and mobile source emissions than before the pandemic. in closing, i would like to highlight that the u.s. atmospheric science community, including many acs earth and space chemistry authors, has rapidly adapted and is contributing in a number of valuable ways on interdisciplinary teams to address the current crisis. the atmospheric aerosol community has lent their expertise and laboratory equipment to the testing of materials for homemade masks for their ability to prevent the spread of respiratory droplets or inhalation of infective aerosols. others have been involved in testing the performance of n respirator masks after sterilization for reuse, or the small-scale manufacture of ppe, such as face shields. aerosol scientists have also weighed in to the public discussion about respiratory aerosols and the airborne spread of sars-cov- indoors and outdoors. , experts on air quality and climate have shared insights with the media, discussing the evidence for the impacts of the pandemicrelated shutdowns on the environment and implications for future environmental policy. finally, as the academics among us have rapidly adjusted to online education and the new needs and concerns of their students, many have developed and openly shared educational materials online. although we remain socially distanced for now, it has been heartening to see the community come together in this time of acute human and societal need. v. faye mcneill orcid.org/ - - - complete contact information is available at: https://pubs.acs.org/ . /acsearthspacechem. c notes views expressed in this editorial are those of the author and not necessarily the views of the acs. turbulent gas clouds and respiratory pathogen emissions: potential implications for reducing transmission of covid- why pollution is plummeting in some cities but not others is the covid- lockdown really decreasing air pollution in india? earther can atmospheric pollution be considered a co-factor in extremely high level of sars-cov- lethality in northern italy? exposure to air pollution and covid- mortality in the united states covid- implications for epas enforcement and compliance assurance program what's the best material for a mask for coronavirus? the new york times coronavirus at beaches? surfers, swimmers should stay away, scientist says the coronavirus pandemic and aerosols: does covid- transmit via expiratory particles? key: cord- -qybrotg authors: cowell, shannon; jenks, kelly title: beloved things: interpreting curated pottery in diasporic contexts date: - - journal: int j hist archaeol doi: . /s - - -w sha: doc_id: cord_uid: qybrotg historical archaeologists often view curated or heirloom pottery as a frustrating anomaly in the dating of historical-period sites or contexts. fewer pause to consider why the artifacts were curated in the first place, or what their presence reveals about the people who maintained them. drawing on a case study of curated micaceous pottery at a hispanic diaspora site in east-central new mexico, this article argues that investigation of heirloom pottery can offer insights into the functional, familial, and cultural significance of these beloved things. historical archaeologists often view curated or heirloom ceramics with irritation rather than interest because of the way they complicate the relative dating of historical-period sites. stanley south ( : ) acknowledged the likelihood of recovering "a few heirloom pieces" of pottery in collections from sites and sought to account for them through the development of his mean ceramic dating formula. subsequent generations of archaeologists have argued over whether ceramics are even useful for dating sites, in part because of their relatively long use-lives and the greater likelihood of recovering heirloom or hand-me-down items (e.g., adams ; williamson ). yet, while historical archaeologists often mention heirloom ceramics in the context of archaeological dating, few pause to ask why these artifacts were curated or what their presence reveals about the people who maintained them. in this article, we consider these questions in our analysis of curated micaceous cookpot fragments recovered from a late nineteenth/early twentieth-century hispanic diaspora community in east-central new mexico. through this analysis, we argue that the investigation of heirloom pottery can offer new insights into the functional, familial, and cultural significance of these beloved things. anthropologists have long been interested in what things reveal about the people who make, exchange, use, and discard them. marcel mauss ( ) considered how reciprocal gift exchanges function to create and maintain social relationships in so-called traditional societies. a generation of anthropologists inspired by karl marx focused on the commodification of things within capitalist societies, considering its many social and political consequences. in his landmark edited volume the social life of things, arjun appadurai ( ) questioned the tendency of scholars to dichotomize gifts and commodities, encouraging researchers instead to consider the varied social relationships that are revealed when focusing on the objects rather than the subjects who make and exchange them. igor kopytoff ( ) , writing in the same volume, argued that commodification is a process that is best understood by taking a biographical approach to the study of objects. tracking a single object throughout its lifespan allows one to understand how the same item can be made into a generalized, impersonal commodity or a singular, inalienable thing at different points in time, and may hold different values and meanings simultaneously when viewed by different people. as an example of the latter, kopytoff ( : ) notes that a jeweler would likely view his watch as just another commodity, even though kopytoff inherited this object from his father and it is, to him, a precious heirloom. for the purpose of the current study, we are less interested in exploring the early history of the micaceous pots as commodities-their production and trade-than we are in understanding why they became heirlooms and what it means that they were kept and curated. the english anthropologist daniel miller (who began his career in archaeology) describes materiality as a theoretical perspective that attempts to understand people's ideas, values, and relationships through the lens of material culture. as he says, "an anthropologist does not start from individuals who create their worlds. we start from the historical processes and material order which create those characteristic individuals and their expectations. in short, material culture matters because objects create subjects much more than the other way around" (miller : ) . miller draws on pierre bourdieu's ( bourdieu's ( , notion that our daily practices express and reinforce our underlying values, noting that material objects play a significant role in this process because they are so often routine and unseen, allowing them to "determine our expectations by setting the scene and ensuring normative behavior, without being open to challenge" (miller : ) . in this way, everyday items like cooking pots can be significant, even if the people who used them may not have thought so, because they shaped those people's domestic environments, cooking practices, and cuisine in ways that subconsciously shaped and reinforced their social and cultural identities. the micaceous pots that are the focus of this study were nonlocal objects transported to the site by hispanic new mexicans who ventured beyond their traditional homeland, defined by spanish and mexican land grant communities, to take advantage of new american homestead laws. while still technically within their home country, they were effectively immigrants in this new place, adapting to an alien legal system, strange neighbors, and a landscape with which they were not intimately familiar. migration disrupts the pattern of everyday life, often fracturing what bourdieu ( ) refers to as doxa-a set of unquestioned and implicit ideas about the order of the natural and social world. in this moment of crisis, migrants may find their attention drawn to everyday objects and practices and the comfort they provide. implicit ideas and identities that were embodied through these daily practices now become explicit, as migrants seek to redefine themselves in a new setting by consciously engaging with familiar objects and/ or performing familiar tasks. archaeologist magdalena naum ( : ) describes it this way: "if certain routines and artifacts are salvaged in this situation, they may receive a new meaning transcending the ordinariness of the everyday. they may become a point of anchorage for immigrants in their novel environments, ways of expressing identities, and at the same time they may act as reminders of the past." this shift in the significance of everyday objects and practices among migrants is described in many contemporary studies of migration, diasporas, and material culture (e.g., miller ; parkin ; tolia-kelly ) . theano moussouri and eleni vomvyla ( : ) consider the significance of items "from home" possessed by albanian immigrants in greece, observing that these objects and photographs "acquire prominent status as touchstones of cultural and biographical narratives enacting embodied, sensory connections with sites, sounds, environments, textures, and landscapes of enfranchisement and belonging." these sensory connections to familiar places and better times help them cope with the social "exclusion and stigmatization" (moussouri and vomvyla : ) that is often part of the immigrant experience. objects relating to food often hold particular significance, as the preparation and consumption of these foods evoke many senses at once. elia petridou ( ) describes how greek students in england solicit care packages of food from home and prepare them for friends in an effort to evoke feelings of home and belonging in a natural and cultural landscape that feels utterly foreign. as she says, "home becomes a steady point of reference in the search for meaning, a starting point for the journey of self-creation. food serves this purpose by providing the sense of stability and continuity of the idealized home" (petridou : ) . closer to our study area, raquel rubio-goldsmith ( ) describes how mexican women immigrants to the united states in the early twentieth century sought comfort and control over their new environments through the traditional domestic task of creating and maintaining gardens seeded with familiar vegetables, herbs, and flowers. forced to deal with the shift from being part of the conquering (spanish) population in mexico to becoming part of a conquered and disparaged (mexican) population in the united states, these women "built their [garden] walls and within re-created their own version of 'civilization'" (rubio-goldsmith : ) . familiar, everyday objects and practices not only help anchor migrants as they adapt to new places, they also help them maintain their sense of connection to people left behind. as miller ( : ) says, "people exist for us in and through their material presence," thus material objects are an integral part of all social relationships. rubio-goldsmith ( : ) notes that mexican women migrated to the united states with seeds for their gardens, and explains that seeds like these were "passed from mother to daughter from time immemorial." thus, a squash or a rose planted in the garden was more than just a simple plant-it was a living expression of the relationship between mother and daughter, between home and homeland. these and other memories kept women attached to their gardens-the place where a stillborn child was buried, the tree planted by a son later killed in war, the countless ways that relationships with family were embedded in places, plants, and things. sociologist helen holmes ( ) argues that a significant but understudied aspect of families is the active role that everyday material objects play in reproducing and sustaining kinship. she employs a performative definition of family as something that we do, and observes that one of the key ways that we perform our familial relationships is by passing on objects. by focusing on these objects and the contexts of their use, holmes identifies four types of "material affinities": ) inherited mundane objects in use, ) handed down objects, ) repurposed objects, and ) objects as family reminders. the first category of objects have some sentimental value but are more often valued for practical reasons; nevertheless, the physical act of using these items serves as a routine reminder of the current owner's familial ties with the (deceased) previous owner. the second category comprises items that are handed down between living kin, which likewise provide opportunities to remember, perform, and reinforce kin ties. the third category, repurposed objects, consists of upcycled items handed down from family members. while these are "not treasured keepsakes to be preserved without change" (holmes : ) , part of their value is sentimental because they evoke the relationship between the current and original owners. finally, the last category consists of curated objects valued for their associations with family-for example, a set of porcelain received as a wedding gift or a grown child's former favorite toy. by focusing on family through the lens of inherited or curated objects, holmes ( : ) shows how "kinship can be layered within everyday objects, and their sentimental value realized and celebrated through their use." while holmes describes how inherited objects can help maintain relationships between the living and recently deceased, lin foxhall ( ) argues that objects can also create and sustain emotional ties in the absence of face-to-face relationships. foxhall offers a modern example of a wooden spoon inherited from her grandmother's sister, a woman who died before foxhall was born. despite never meeting her, she came to know and admire her great aunt through her grandmother's stories and through the object-the spoon-that held and evoked these memories and affectionate feelings. her daughters, in turn, never met their great-grandmother but likewise came to know and feel connected to these women through the stories connected with this spoon. foxhall ( ) then considers the emotional significance of loom weights in ancient greece-artifacts that young women inherited, used, and brought with them after marriage as they moved in with their husband's family (also see tarlow : ) . drawing on historical and archaeological evidence, foxhall ( ) argues persuasively that these seemingly banal artifacts could become charged with emotion and through these objects these sentiments could transcend time, connecting women to distant or deceased kin in the same way that her daughters felt connected with their maternal lineage through a shared wooden spoon. finally, while material objects (artifacts) have social and cultural value, they have practical value as well. in writing about contemporary theories of materiality and object agency, lars fogelin ( : ) reminds archaeologists to also consider "how the specific materiality of an object shapes its agency and the social implications of that agency." not all objects are equally likely to be transported to new places or passed down among family members. likewise, not all imported or inherited objects are equally likely to be kept, used, and valued. utilitarian objects of the kind described by foxhall ( ) and captured in holmes' ( ) inherited mundane objects in use are valued primarily for their utility, and it is through the everyday use of these objects that people's relationships with family, culture, or homeland are performed. thus, in considering the micaceous utility ware fragments that are the focus of this study, it is important to consider not just those relationships, but also the performance characteristics of the pots themselves that enabled and encouraged their continued use. in , kelly jenks directed field school students in documentation, surface collection, and test excavation activities at the site of los ojitos, located in the middle pecos river valley in east-central new mexico (jenks et al. ). this rural community was first settled by hispanic homesteaders in the late s and abandoned less than a century later after dam construction downstream threatened the floodplain. archaeological fieldwork targeted the village core, which includes remnants of the earliest homesteads, the cemetery, and several of the springs (ojitos) that gave the community its name. surface collection and excavation produced , artifacts and ecofacts consisting mostly of metal, glass, and ceramics. over % of the ceramic fragments derive from american-or english-manufactured serving and cooking vessels that were commonplace in the area during the late nineteenth and early twentieth centuries. six percent of the fragments derive from micaceous earthenware cooking pots that were produced, traded, and used by hispanic and native american women in northern new mexico, especially during the late eighteenth and nineteenth centuries (cowell ) . these micaceous pots, which appear to have been brought to los ojitos by the earliest settlers and maintained over several generations, are the focus of this case study. the spanish conquered and colonized new mexico in , establishing a series of settlements along the rio grande that would form the core of new mexico's "hispano homeland" (frank ; meinig ; nostrand ; rodríguez ; van ness ) . after centuries of hispanic political dominance, these lands were conquered by american forces in and administered as an american territory following the end of the mexican-american war. despite promises by the united states to honor the property rights of former mexican citizens, american land speculators targeted and eventually acquired lands held in common by hispanic communities (ebright ) . after , hispanic new mexicans sought to recoup their losses by using the homestead acts to settle and claim parcels of public land. in seeking these new lands, many hispanic families left their home communities and ventured down the pecos river and out toward the plains, where they encountered and competed with white american settlers locally known as "anglos." the rural community of los ojitos was established by some of these hispanic homesteaders along a stretch of the middle pecos river in this hispano-anglo borderland (fig. ) . urban segregation, especially in new mexican towns and cities established by anglos, peaked in with highly clustered racialized settlement (nostrand : - ). rural communities in new mexico were similarly segregated along ethnic and racial lines. los ojitos, which reached a peak population of residents within families in (jenks et al. : ) , was a predominately hispanic community. more than % of all residents were native new mexicans of hispanic descent, and spanish was the only language spoken by most residents throughout the village's history. the residents maintained a traditional mixed economy, farming the river valley and grazing livestock on the surrounding plains; in census records, most heads of household self-identified as day laborers, farmers, ranchers, or sheep or cattle herders. most, if not all, of the residents were practicing catholics-in contrast to the predominately protestant anglo immigrants-and evidence of their faith is recorded on petroglyphs, tombstones, and in religious medallions and artifacts observed in or collected from the site (jenks et al. ; jenks ) . residents who attended church would have traveled to puerto de luna, a majority-hispanic town located about mi ( km) upstream, which was the epicenter of religion and commerce for the area's rural hispanic communities (del fierro duran : - ; o'mack ) . after , when the rock island and el paso railroad was built through santa rosa, the commercial center shifted north to that hispanic-majority town (o'mack ) . in contrast, fort sumner-a town located about mi ( km) downstream from los ojitos, and with stronger connections to the anglo community-played a less central role in that village's history (jenks et al. : ; o'mack ) . thus, while residents of los ojitos lived far from the nucleated center of the "hispano homeland" (meinig ; nostrand ), they maintained close economic, religious, and social ties to the hispanic new mexican community (del fierro duran : - ; jenks et al. ) . while hispanic new mexicans were legally designated "free whites" by the united states in accordance with the treaty of guadalupe hidalgo, they experienced considerable racial prejudice under american rule (clark (clark , rodríguez ) . throughout the fight for new mexican statehood and self-government in the late nineteenth and early twentieth centuries, many americans characterized hispanic new mexicans as mixed-blood mestizos unfit for citizenship without the prerequisite whiteness (mora ; nieto-phillips : ) . hispanic identity thus came to be defined by this paradox between "the legal construction of mexicans as racially 'white' alongside the social construction of mexicans as non-white and as racially inferior" (gómez : ) . the social and political marginalization of hispanic new mexicans within the state made them more reliant on each other for supportespecially at the margins of the hispano homeland, where anglo families equaled or even outnumbered hispanic residents. when the geopolitical border between the united states and mexico "crossed" hispanic new mexicans, the legal practices of a new regime forced people from within the core territory of the hispanic homeland into peripheral, less-familiar lands controlled by an antagonistic government. while the inhabitants of los ojitos were not immigrants in a strict sense of the word, as a newly subaltern population displaced by american land policy to the edge of their homeland and subjected to the encroachment of american people, norms, and goods, they likely experienced "diasporic forms of longing, memory, and (dis)identification" (clifford : ) . this feeling among hispanic new mexicans is often described as "querencia" (e.g., fonseca-chávez et al. ), an old spanish term for attraction or longing that has come to be associated specifically with the longing for homeland, or the "feeling of safety and belonging that a person has for a specific place" (rodríguez : ) . this feeling of querencia-of longing for the hispano homeland-remains powerful among the descendant community to this day; sylvia rodríguez ( : ) writes, "at the heart of modern nuevomexicano identity formation is the paradoxical condition of being simultaneously displaced and place-based." residual micaceous clays found in the sangre de cristo mountains in northern new mexico have supplied potters with a durable medium for utilitarian cookpots for centuries. sangre de cristo micaceous wares were produced throughout the upper rio grande valley by pueblo, jicarilla apache, and hispanic potters during the seventeenth, eighteenth, and early nineteenth centuries (eiselt ; eiselt and ford ; eiselt and darling ) . as a semi-nomadic group exclusively specializing in large micaceous vessel production, jicarilla apaches often set up ceramic production camps alongside hispanic consumer villages in northern new mexico and traded the finished vessels for food or other products from the village (eiselt and darling : ) . large cooking pots, water jars, and serving bowls produced by jicarilla apache potters comprise the majority of micaceous ceramic assemblages analyzed from hispanic village sites on the northern rio grande dating to the first half of the nineteenth century (eiselt and darling : ) . american annexation of the southwest in the mid-nineteenth century brought widesweeping material changes, disrupting local barter economies with new technologies and distribution patterns and ultimately leading to the abandonment of micaceous ceramic production and trade as a means of subsistence. while historical evidence points to continued production of micaceous ceramics into the s by a band of jicarilla apaches on the upper pecos river near san miguel del vado (abel (abel : , bender ) , decades of displacement and famine followed by forced removal to the jicarilla apache reservation in precludes the possibility that these potters traded with consumers at los ojitos (anderson ; rebolledo et al. ) . this leaves only the possibility that micaceous pots obtained in trade in the upper pecos valley during the mid-nineteenth century were brought by early settlers downstream to los ojitos (cowell ) . micaceous ceramic sherds were recovered from several contexts at los ojitos, including excavated deposits within three residential structures (numbers , , and ) and in test units and surface refuse scatters surrounding structures and (fig. ) . macroscopic analysis confirmed that these fragments were sangre de cristo micaceous wares, even though los ojitos is located outside of their typical distribution area (cowell ) . although some hispanic women on the upper pecos riverparticularly those with close familial ties to indigenous potters-may have produced their own pottery (carrillo ) , there is no archaeological evidence of pottery production at los ojitos. instead, these vessels appear to have been brought to los ojitos by the hispanic families who settled this site in the late nineteenth century. contextual clues indicate that these micaceous pots were curated and deposited decades after their arrival at los ojitos. a cimarron micaceous rim sherd, attributed to a vessel produced by jicarilla apache potters (likely before the s), was recovered during excavations in structure alongside diagnostic artifacts dating - (cowell : ; jenks et al. : ) . a concentration of sangre de cristo micaceous jar sherds, including several painted with a red tempera paint (fig. ) , was recovered from fill just above a hard-packed earthen floor in structure (fig. ) , alongside mid-twentieth century artifacts such as a leather glove, part of a car engine mount, black plastic music record fragments, and a complete vicks vaporub jar dating between the s and s (cowell : ; jenks et al. : - ) . another sangre de cristo sherd was recovered from a test unit placed over a traditional hispanic adobe corner fireplace within structure (fig. ) in a room likely constructed after (cowell : ; jenks et al. : ) . that these micaceous ceramic fragments were discarded alongside twentieth-century artifacts suggests that they were maintained and used for several decades-a long time for even the most durable utilitarian ceramics (foster : ) . these micaceous cooking pots were clearly quite rare on the middle pecos. low frequencies of micaceous ceramics are found at los ojitos, both relative to sites within the traditional area of trade and relative to the frequencies of mass-produced american tableware sherds at the site. the first generations of hispanic women who settled los ojitos from the late s onward likely brought pots from the last generation of traditionally produced and traded micaceous ceramics from northern new mexico. these ceramics would have been virtually impossible to replace on the spatial periphery of the hispanic new mexican homeland in the decades after jicarilla apaches were forcibly relocated to reservations. the maintenance of micaceous ceramics is a testament to the importance they held for the women of los ojitos: these vessels were preferentially preserved and curated over decades of use. so, why do micaceous cookpots persist, appearing in late contexts at far-flung homesteads? american land practices and discrimination brought disruption to everyday hispanic life, forcing adaptation to new legal realities and migration to peripheral borderlands. as hispanic homesteaders packed their wagons and trekked down the pecos, they faced a new social and economic paradigm, a new set of neighbors, and new ways of acquiring goods. a micaceous cookpot-formerly accepted as an everyday, replaceable tool and perhaps taken for granted-became, through the fracturing of bourdieu's ( ) doxa, something irreplaceable, precious, and laden with cultural significance and memories of home. unique material qualities inherent in these utilitarian micaceous pots-the earthy flavor they impart on foods, their glittering visual impact, and their literal construction from the earth of the homeland-made these tools particularly potent everyday reminders of past homes and hearths. comments celebrating the superiority of micaceous bean pots are common in both historic and modern new mexico, where these vessels are treasured by cooks and potters alike. to this day, new mexican ceramic artists produce micaceous pottery for sale, using the distinctive taste it adds to cooked foods as a selling point. the late felipe ortega, a renowned jicarilla apache potter, considered micaceous pots to be an essential tool for making palatable beans: "the beans taste better!" (anderson : ) . artist martha romero ( ) of nambé pueblo described the special flavor imparted by micaceous cookware as earthy, mineral-rich, and appealing to "anyone who ate dirt as a child." the pores of micaceous pots hold onto flavor, and each dish prepared leaves a visual and aromatic residue that transfers flavors from the past into new meals during the process of cooking. these characteristics place micaceous ceramics in a category exclusive of other types of cookware-there are no substitutes in american cookware or local non-micaceous earthenwares. according to duane anderson ( : ) , "if micaceous pots were not so ideally suited for cooking, they probably would have disappeared, as many other varieties did, when metal pots and pans made their way into the southwest on the santa fe trail and later by way of the railroads." the preeminence of micaceous bean pots lies in the physical qualities of the mica itself. source materials identified in eiselt's geochemical sourcing of historic northern rio grande micaceous ceramics came from the vadito group, a formation common to both the sangre de cristo and san juan mountains that contains fine residual clays with up to % residual muscovite content (eiselt and darling ) . mica's reputation in both historical and modern potting communities as a resilient and durable temper perfect for cookpots (eiselt and darling ; warren ) is supported by west's ( ) experiments with various tempering materials. west ( : ) suggests that the deliberate use of primary clays with wide aplastic size ranges and abundant aplastics in the rio grande region "appears to be purposeful with the objective of obtaining qualities of improved thermal shock resistance." this makes micaceous pots both durable and user-friendly, extending their longevity beyond the usual lifespan of an earthenware cookpot. thus, like other objects in holmes' ( : ) category of inherited mundane objects in use, "these objects are kept because they keep working-they are good at what they do, therefore there is no need to replace them." the methods used to cook with micaceous ceramics comprise part of a suite of culinary practices unique to new mexico. slow initial heating and low, sustained temperatures for up to six hours of cooking protect the pots from breakage and cook beans and other foods to perfection (fig. ) . the persistence of these practices suggests adherence to a set of beliefs about what kinds of vessels are essential to the production of certain foods. in the mid-nineteenth century, as hispanic families were beginning to migrate down the pecos river, an american circuit judge commented on the ubiquity of these cookpots in new mexico, writing, "they cook almost universally in earthen vessels, which bear the general name of tinaja, and it is a rare thing to see any other description of culinary articles" (davis (davis [ : ). generations later, near the end of the los ojitos occupation, fabiola cabeza de baca gilbert ( gilbert ( [ , [ ]) mentioned the use of earthenware pots in her early cookbooks, which are among the earliest and most celebrated cookbooks published on new mexican cuisine. as she says, "the secret of tasty beans lies in cooking them just right…at low temperature and for a long time" (cabeza de baca gilbert [ : ). referencing a time-honored culinary tradition with indigenous roots, micaceous ceramics hearken back to memories of familiar new mexican foods and the everyday tools and methods used to create them. the sensory-laden process of preparing a dish within a micaceous pot-soaking beans with water from an open cistern, practicing proper care and storage of the pot, slow heating and expert control of a fire, the sounds of simmering liquids and wooden tools against earthenware-were likely a calming force, reminiscent of past homes and routine behaviors. cuisine refers not only to the edible outcomes of a food tradition but also to the process used to cook or produce the foods that people eat. cooking processes are preordained by culinary identity, part of an "aesthetic code" (crowther : ) generating expectations about how a particular food should smell, taste, feel, and look following the chemical, physical, and hydration changes created by heat. specific recipes or learned methods for cooking a particular dish create an idealized image or expectation about the sensory features of a finished food item (crowther : ) . crown ( ) describes cuisine as a cultural construct organizing how foods should be prepared and served, encoding anticipated flavor and texture outcomes defined by tradition. the experience of diasporic displacement heightens this embodiment of memory in food or food-related items, producing "gustatory nostalgia" (holtzman : ) defined by a sensual recall of past food experiences in the homeland (petridou ) . for example, a hispanic new mexican woman named cesaria gallegos interviewed by the works progress administration federal writers' project in wistfully assigned an old national identity to her beans, stating that "there is no food como la mexicana frijoles," while lamenting the loss of "the food they used to eat" (rebolledo et al. : ) . for the first generation of women at los ojitos, preparing and serving beans in traditional micaceous pots would have imbued their new homes on the middle pecos with "the smells and tastes of a lost homeland" (holtzman : ) . in subsequent decades characterized in part by the experience of social and political discrimination by anglos, maintenance of these pots and culinary traditions may have taken on an added layer of significance (clark (clark , . as anglos within and outside of new mexico disparaged mexican culture and pushed for their cultural assimilation and americanization (deutsch : - ) , the women at los ojitos might have chosen to maintain certain new mexican culinary traditions as a way of claiming and celebrating their cultural heritage. in her study of mexican women who experienced similar discrimination after immigrating to new mexico in the early twentieth century, raquel rubio-goldsmith ( ) observed that these women responded not by assimilating and eliminating or minimizing their traditional cultural practices but by recommitting to them. in response to the hostility surrounding them, these twentieth-century norteñas built and planted traditional gardens outside of their homes, and inside, "they maintained their worship of god, the proper food, and the proper care of family" (rubio-goldsmith : ). in the same way, the maintenance of micaceous pottery and associated culinary practices at los ojitos might have been a conscious and deliberate reaction by some village women to the cultural prejudice of neighboring anglo-americans. micaceous ceramic vessels at los ojitos, as part of the last generation of pots produced and traded through traditional means in northern new mexico, represent material traces of the hispanic homeland as it changed under the american regime. the loss of familiar tools that previously had been easily procured forced women to curate micaceous ceramics until they broke, and, once broken, to adapt to american-produced substitutes like enamel pots or cast iron pans with a new suite of cooking techniques (fig. ) . another new mexican cookbook written in by cleofas m. jaramillo specifies using earthen pots for slow-cooking several dishes though, interestingly, recommends using a "white enameled pot or new tin coffee can" (jaramillo : ) for cooking dry beans. another common lament from the mid-twentieth century about beans burned in castiron pans or enamel pots may speak to a generation of women adapting to this new technology. nasario garcía ( : ) tells a story of his grandmother warning him not to marry "a girl who burns the beans," inspired by a local woman who often plagued her community with the pervading smell of burning frijoles. while mass-produced american cookware may be adequate to the task of cooking traditional new mexican cuisine, the mastery of new cooking tools often involves an uncomfortable learning curve. more importantly, no metal pot can impart the same earthy flavor as the traditional micaceous bean pot. this forces the cook to adjust to a new definition of her own cooking prowess, and her personal and familial cuisine suffered from a new lack of traditional, expected flavor. archaeological evidence recovered at los ojitos suggests both maintenance of traditional new mexican cuisine and adoption of american foods and food technologies. the women of los ojitos shifted away from the traditional practices of drying meat and plant foods, avidly adopting canning technologies as a replacement, and used store-bought canned goods such as lard and baking powder. industrial tableware and kitchenware imported from the eastern united states, including yellowware mixing bowls, enamelware, fancy porcelain, and crockery fragments, were far more plentiful than micaceous ceramics at los ojitos (jenks et al. : ) . plates, utensils, and additional decorated tableware suggest a shift from traditional communal serving of stews to preparation and individual service of drier foods (jenks et al. : ) . however, evidence of household-level butchering of cattle and sheep/goats at los ojitos suggests a continued preference for stew cuts (jenks et al. ) , which were likely prepared in traditional micaceous vessels. overall, the assemblage suggests adoption of american food technology alongside preservation of traditional new mexican ingredients, with the use of historical micaceous ceramic cookware as a significant material outlier. the relative rarity of these ceramics among new tools and tableware would have made them stand out in kitchens at los ojitos, making explicit their inherent significance as touchpoints for cultural identity. as naum ( : - ) remarks in the case of baltic pottery in scandinavia, "displacement constituted a viable context for such 'revealing'… [of] vessels as silent reminders of the homes they had left behind, a material element inseparably related to their identity as immigrants." as literal pieces of the homeland imbued with memories of past meals, these everyday utilitarian pots conveyed old, earthy flavors to new landscapes, reinforcing continuity through the performance of culinary traditions. micaceous ceramic vessels used to cook beans and stews represent both the maintenance of a traditional new mexican culinary practice and a prized, durable artifact category. traditional food preparation methods and the objects used to replicate them were passed down between generations of hispanic women, enabling them to provide their families with well-prepared, nourishing staple foods just as their ancestors and relatives had done for centuries. hispanic women were traditionally responsible for procuring and storing all the necessities for a well-appointed kitchen, including ceramic cookware and tableware. when heirlooms are inherited tools meant to be used, such as ceramics associated with food preparation, they communicate strong expectations between female relatives about "productivity and social re-productivity" (lillios : ) , about the right ways of cooking and the right kinds of foods to eat. individual or familial techniques elaborate on standardized culinary forms, injecting personal preference, skill, and experience into what appears on the kitchen table. culinary practices provide intergenerational ties to traditional hispanic new mexican practices while emphasizing women's responsibility and authority in sustaining their families. micaceous pots were fundamental to supporting new households in far-flung places, especially when removed from everyday interaction with relatives and when faced with the social, emotional, and economic challenges of moving to a new place as a newly marginalized group. in his study of hispanic pottery traditions, charles carrillo ( ) routinely encountered hispanic families living in the upper pecos river valley who owned - -year-old micaceous pots, often passed down to them by older female relatives. in one example, "mrs. trujillo used a micaceous bean pot that she had inherited from her mother until the bottom wore through in the s. unable to acquire a new pot, she began using a metal pot for her cooking" (carrillo : ) . several of carrillo's informants produced late nineteenth-and early twentieth-century curated micaceous bean pots attributed to both hispanic and jicarilla apache producers, while other ceramic types of similar temporal range and utilitarian character were not encountered. this speaks to the possible durability and longevity of micaceous ceramics, but also suggests a desire to preserve these precious and value-laden ceramics inherited from female relatives. in a diasporic context, the meanings embodied by heirlooms can be heightened by feelings of displacement, fragmentation, and loss. as in rubio-goldsmith's ( ) case study of mexican women who migrated to the united states, heirlooms often functioned as reminders of past relationships and ways to maintain and perform kinship over space and time. as objects used primarily by women, who often take on "the role of valuing and organizing passed on items, and the emotional forms of labor this entails" (holmes : ) , micaceous ceramics link both collective ancestral histories and individual intergenerational relationships in a single everyday object. "[t]hese material affinities are heightened through objects put to use; as engaging objects in practice reveals how materiality and relationality are folded and layered together within the sensory and material qualities of objects" (holmes : ) . using micaceous ceramics invoked shared memories of cooking together in a lovedone's distant kitchen, rife with associations of familiar smells and sounds, hearty nourishment, and comforting warmth. in this way, these curated artifacts embodied memories and emotions associated with family members, providing a way to interact with a relative and maintain a social relationship by proxy, transcending the barriers caused by migration, death, and the passage of time. seasoned with a historical residue of past meals and memories, micaceous pots provided a way to make food the right way with tastes and smells remembered from childhood. the material qualities of micaceous pots and their sentimental value contribute to their longevity and persistence in hispanic new mexican sites many decades after their manufacture. in times of stress, migration, or disenfranchisement, certain curated artifacts and the processes involved with their use become salient points of contact with past sensations and memories, cultural identity, and familial relationships. this case study involves a longstanding indigenous technology-micaceous cookpots-adopted as traditional tools for the production of hispanic new mexican cuisine during the spanish and mexican periods. in a new spatial and social context, situated on the middle pecos river in the hispano-anglo borderland, these micaceous pots became rare and irreplaceable due to american economic and social disruption. these curated cooking tools became vessels for memories of past meals and sensory experiences unique to the hispanic homeland and its culinary traditions, as well as a means of preserving and honoring familial relationships despite separation. rudolfo anaya ( anaya ( [ ), the late author of the classic novel bless me, ultima, grew up in a small village on the pecos river in the s-a place not far from and very similar to los ojitos near the end of its occupation. in his essay "querencia, mi patria chica," written as a foreword to the edited volume querencia: reflections on the new mexico homeland, anaya ( :xv) describes querencia as a "love of home, love of place," encapsulating a narrative about one's origins centered on home, family, and heritage, and a physical and spiritual place to return to as a source of safety and strength. he extends querencia explicitly to the hispanic new mexican diaspora and to everyone on the move, displaced, deployed, or incarcerated, writing that "one can make querencia wherever one lives" (anaya :xviii) . as an element of emotional life that can be deliberately constructed, especially in times of upheaval, querencia offers an understanding of one's belonging in multiscalar familial, social, and historical landscapes. when creating a new life and new home in a new place, decisions to keep and maintain specific artifacts or items reinforce querencia as it lives in material objects. in our experience, family and friends reminisce about cast iron pans the same way hispanic new mexicans reminisced about micaceous bean pots-food prepared with cast iron just tastes better, and the pot's seasoning, by definition, is a resilient historic deposit that imbues foods with inherited flavors. this clued us in to a deep-rooted, nearuniversal attachment to certain traditional "comfort foods," or the tools and processes used to create them, especially potent in times of stress or change. drafting this article became urgent to us in the early days of the covid- pandemic as we found ways to cope with the new-found realities of stay-at-home orders and socioeconomic upheaval. ubiquitous emotional regulation responses to these stresses involved a return to traditional means of sourcing and preparing food items, such as baking sourdough bread, planting a victory garden, or canning produce. again, in times of stress or disruption to everyday life, we turn to older methods for practical reasons-to eke out subsistence from forgotten pantry items when grocery trips are ill-advised or when a future paycheck is not guaranteed-but also to re-enact a comforting, prosaic ritual resurrected from ancestral kitchens, real or idealized. in her sapiens article "can archaeology explain the bread baking craze?," robyn cutright ( ) suggests that "[p]eriods of stress and change can prompt people to hold on to their diets and culinary traditions…as a way of buffering uncertainty and upheaval." the act of creating a dish through traditional means can provide a few moments of individual control over a routine process as the world spins out of control, "preserv[ing] a sense of stability and social cohesion even as life outside the home change[s]" (cutright ) . we find comfort in older technologies and processes because they sustained our ancestors physically and emotionally for centuries, and in many ways, similarly self-determined, self-affirming, subsistence-level culinary activities have disappeared from our lives with economic and technological changes. in the context of historical archaeology, this may be one of many potential motivations behind the curation of artifacts beyond their typical lifespan and expected spatial range. the last four centuries of colonialism resulted in voluntary or involuntary movement of populations across the globe, just as the last two centuries of rapid technological change and globalization generated new tools and goods to be adopted readily or reluctantly. most sites studied by historical archaeologists hold material evidence of curation decision-making by relocated or displaced people who experienced stress, social isolation, or discrimination in their new environments. james deetz ( : ) , when faced with a mean ceramic date at the parting ways site pre-dating the actual occupation by nearly thirty years, suggested that the high-status assemblage might have been hand-me-downs from elite neighbors to the ex-slave occupants of the site. he urged historical archaeologists to investigate such discrepancies since a "search for the explanation might well result in a better understanding of the material in cultural or behavioral terms" (deetz : ) . reconsidering seemingly anachronistic items pre-dating the occupation of an archaeological site can reveal significant social and emotional realities of the people who lived there. a problematic, anachronistic artifact presents an opportunity for reinterpretation from a social and emotional lens to explore how people came to define themselves in new environments. what do people choose to maintain or discard? what do people hold on to, and why? these decisions, we suggest, are based not only on practical purposes, but can potentially stem from lived social, emotional, and cultural realities often heightened and highlighted by change and disruption. in the case of los ojitos, women may have maintained micaceous bean pots for both their functional preeminence in the preparation of new mexican cuisine and for their embodiment of querencia, made poignant by disconnection from traditional homelands and kin. the official correspondence of james s old santa fe: a magazine of history dating historical sites: the importance of understanding time lag in the acquisition, curation, use, and disposal of artifacts bless me querencia: mi patria chica all that glitters: the emergence of native american micaceous art pottery in northern new mexico introduction: commodities and the politics of value a study of the jicarilla apache indians - the berber house outline of a theory of practice historic cookery. gibbs smith hispanic new mexican pottery: evidence of craft specialization - lived ethnicity: archaeology and identity in mexicano america on the edge of purgatory: an archaeology of place in hispanic colorado historic 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language of blood: the making of spanish-american identity in new mexico, s- s draft nomination to the national register of historic places for the los ojitos archaeological district. bureau of reclamation mementoes as transitional objects in human displacement the taste of home women's tales from the new mexico wpa: la diabla a pie the hispano homeland debate revisited history, memory, and querencia lecture presented november , at the indian pueblo store (formerly shumakolowa native arts civilizations, barbarism, and norteña gardens the archaeology of emotion and affect location processes of identification: studying the precipitates of re-memory through artefacts in the british asian home hispanos in northern new mexico: development of corporate community and multicommunity collected papers in honor of erik kellerman reed temper, thermal shock and cooking pots: a study of tempering materials and their physical significance in prehistoric and traditional cooking pottery dating the domestic ceramics and pipe smoking related artifacts from casselden place publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgments the authors would like to thank the descendants of the los ojitos community, the students and staff who participated in fieldwork at los ojitos, and archaeologists jeffery hanson and mark hungerford at the bureau of reclamation's albuquerque office who permitted and supported this and previous projects. particular thanks are given to ernesto chavez, who shared his memories of los ojitos in an oral history interview with tara del fierro duran, as well as clarence cruz (ohkay owingeh) and martha romero (nambé pueblo), who shared their artistic expertise and practical knowledge of micaceous ceramics. we dedicate this article to mark hungerford, who steadfastly supported this site, our students, and members of the descendant community. may he rest in peace. key: cord- -yp x zwi authors: ngonghala, calistus n; iboi, enahoro; eikenberry, steffen; scotch, matthew; macintyre, chandini raina; bonds, matthew h; gumel, abba b title: mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the novel coronavirus date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: yp x zwi a pandemic of a novel coronavirus emerged in december of (covid- ), causing devastating public health impact across the world. in the absence of a safe and effective vaccine or antivirals, strategies for con- trolling and mitigating the burden of the pandemic are focused on non-pharmaceutical interventions, such as social-distancing, contact-tracing, quarantine, isolation and the use of face-masks in public. we develop a new mathematical model for assessing the population-level impact of the aforementioned control and mitigation strategies. rigorous analysis of the model shows that the disease-free equilibrium is locally-asymptotically stable if a certain epidemiological threshold, known as the reproduction number (denoted by rc), is less than unity. this equilibrium is globally-asymptotically stable, for a special case of the model where quarantined-susceptible individuals do not acquire covid- infection during quarantine, when rc is less than unity. the epidemiological consequence of this theoretical result is that, the community-wide implementation of control interventions that can bring (and maintain) rc to a value less than unity will lead to the effective control (or elimination) of covid- in the community. simulations of the model, using data relevant to covid- transmission dynamics in the us state of new york and the entire us, show that the pandemic burden will peak in mid and late april, respectively. the worst-case scenario projections for cumulative mortality (based on baseline levels of interventions) are , for new york state and , for the entire us by the end of the pandemic. these numbers dramatically decreased by % and %, respectively, if adherence to strict social-distancing measures is improved and maintained until the end of may or june. the duration and timing of the relaxation or termination of the strict social-distancing measures are crucially important in determining the future trajectory of the covid- pandemic. this study shows that early termination of the strict social-distancing measures could trigger a devastating second wave with burden similar to those projected before the onset of the strict social-distance measures were implemented. the use of efficacious face-masks (such as surgical masks, with estimated efficacy ≥ %) in public could lead to the elimination of the pandemic if at least % of the residents of new york state use such masks in public consistently (nationwide, a compliance of at least % will be required using such masks). the use of low efficacy masks, such as cloth masks (of estimated efficacy less than %), could also lead to significant reduction of covid- burden (albeit, they are not able to lead to elimination). combining low efficacy masks with improved levels of the other anti-covid- intervention strategies can lead to the elimination of the pandemic. this study emphasizes the important role social-distancing plays in curtailing the burden of covid- . increases in the adherence level of social-distancing protocols result in dramatic reduction of the burden of the pandemic, and the timely implementation of social-distancing measures in numerous states of the us may have averted a catastrophic outcome with respect to the burden of covid- . using face-masks in public (including the low efficacy cloth masks) is very useful in minimizing community transmission and burden of covid- , provided their coverage level is high. the masks coverage needed to eliminate covid- decreases if the masks-based intervention is combined with the strict social-distancing strategy. the world is currently facing a pandemic of a novel coronavirus (covid- ) , which started as an outbreak of pneumonia of unknown cause in wuhan city of china in december of [ ] [ ] [ ] . as of april , , covid- (caused by the novel sars-cov- coronavirus) has spread to over countries and territories, causing about . million infections and , deaths [ ] [ ] [ ] [ ] . the united states is now the epicenter of the covid- pandemic, (recording over , confirmed cases and , deaths) within a short time, with new york state bearing the brunt of the us burden (over , confirmed cases and , deaths) [ ] [ ] [ ] [ ] . the first documented confirmed case of the novel coronavirus in the us (a resident who had recently visited wuhan city in china) was reported on january , [ ] , while the first confirmed case in the state of new york was reported on march , . most of the covid- related deaths and severe cases occur in the elderly ( years of age and older) and people with underlying medical conditions [ ] . younger people and frontline healthcare workers are also at high risk of acquiring covid- infection. as with two other coronaviruses that caused major outbreaks in humans in recent years (namely, the severe acute respiratory syndrome and the middle eastern respiratory syndrome [ , ] ), covid- is transmitted from human-to-human through direct contact with contaminated objects or surfaces and through inhalation of respiratory droplets from both symptomatic and asymptomatically-infectious humans [ ] . there is also limited evidence that the virus can be exhaled through normal breathing [ ] . the incubation period of the disease ranges from - days, with about . % of infected people developing disease symptoms within . days of infection [ , [ ] [ ] [ ] . most infections (over %) show mild or no symptoms [ ] . common symptoms of the disease include fever, coughing and shortness of breath for mild cases, and pneumonia for severe cases [ , , ] . in the absence of pharmaceutical interventions (such as a safe and effective vaccine for use in humans and a covid- anti-viral), efforts aimed at containing covid- are focused on the implementation of non-pharmaceutical interventions, such as social-distancing, using face-masks, quarantine of suspected cases, isolation and hospitalization of confirmed cases, contact-tracing and quarantine, mass testing, etc. in particular, since the novel coronavirus is transmitted among people who come in close contact with each other, the implementation of strict social-distancing measures has been the primary tool for curbing the spread of the pandemic. as of april , , stringent social-distancing mechanisms (mandatory lockdowns/ stay-at-home orders) have been imposed in over states of the united states, together with washington dc, guam, and puerto rico (representing over % of the us population; involving approximately million americans) [ ] . the state of new york (the current epicenter for covid- ) has even imposed a fine against people who fail to comply with its stringent social-distancing measures that took effect march , . common social-distancing measures or guidelines being employed in the us include temporary closures of schools and non-essential businesses, avoiding crowded events and mass gatherings, moving in-person meetings online, etc. the city of wuhan lifted its -day strict lockdown on april , (this was done in a phased way, with the first relaxation of measures on february , ). contact-tracing is another major public health strategy for combating the spread of covid- . contact-tracing involves searching for, or identifying, individuals with whom the confirmed case has closely interacted within a certain time frame (e.g., two days prior to the onset of symptoms [ ] ), interviewing, testing, and isolating or hospitalizing them if they have the disease [ , ] . the use of face-masks in public by members of the general population has historically been a common practice to try to limit or combat the spread of respiratory diseases, dating back to at least the h n pandemic of influenza [ ] [ ] [ ] [ ] [ ] [ ] . face masks may have been instrumental in limiting the community spread of the / sars epidemic in asia (particularly in china, singapore, hong kong and taiwan) [ , ] as well as the containment of the covid- pandemic in taiwan [ ] . face-masks have dual purposes. if worn by a susceptible individual, the mask offers efficacy against the acquisition of infection. on the other hand, if the wearer is already infected (but is asymptomatic or mildly-symptomatic and unaware he/she ill), the face-mask offers efficacy against their ability to transmit infection to susceptible individuals [ , [ ] [ ] [ ] [ ] . predicting the course or severity of a pandemic, such as covid- , as well as the realistic assessment of proposed public health intervention strategies for combating them in real time, is a major challenge to both the public health and the scientific community. a number of models have been developed and used to study covid- dynamics. ferguson et al. [ ] used an agent-based model to investigate the effects of non-pharmaceutical interventions on human deaths from covid- , and in reducing burden on healthcare facilities and equipment. they projected that, in the absence of control measures, over % of the populations of the us and great britain might become infected and covid- may cause up to . million deaths in the us. mizumoto and chowell [ ] used a mathematical model and incidence data to study changes in covid- transmission potential as the outbreak progressed through the diamond princess. they obtained a higher reproduction number and noticed a substantial decrease in the effective reproduction number after improved quarantine was instituted. hellewell et al. [ ] used a stochastic model with covid- data to examine the impact of contact-tracing and isolation on disease control, and suggested that for most instances covid- spread can be contained in months if these measures are highly effective. using a stochastic model, kucharski et al. [ ] examined the covid- trajectory in wuhan from january-february , showing a reduction in transmission (a . reduction in the associated effective reproduction number of the model) when travel restrictions were implemented. consequently, there is a need to examine the combined impact of multiple non-pharmaceutical interventions applied together or in sequence. the present study is based on the development of a new mathematical model for studying the transmission dynamics and control of the covid- pandemic in the us (particularly in the state of new york, the epicenter of covid- ). the model takes the form of a kermack-mckendrick, compartmental, deterministic system of nonlinear differential equations. it incorporates features pertinent to covid- transmission dynamics and control, such as the quarantine of suspected cases and the isolation/hospitalization of confirmed covid- cases (similar to the models developed in [ ] [ ] [ ] ). the model, parameterized using available covid- mortality data (more reliable than case data, provides a realistic real-time assessment and estimate of the burden of the pandemic in the us state of new york, in addition to assessing some of the main intervention strategies being implemented in the state (in particular, quarantine, isolation, contact-tracing, social-distancing and the use of face-masks in public). we designed and analyzed a novel kermack-mckendrick-type mathematical model for the transmission dynamics and control of covid- in a population. the model, which incorporates the main non-pharmaceutical interventions being implemented to curtail covid- transmission in a community (such as social-distancing, quarantine of suspected cases, isolation of confirmed cases, contact-tracing, testing and use of face-masks in public), is formulated based on stratifying the total human population at time t, denoted by n (t), into the mutually-exclusive compartments of non-quarantined susceptible (s u (t)), quarantined susceptible (s q (t)), non-quarantined exposed (i.e., newly-infected individuals who do not yet show symptoms of the disease and cannot transmit infection, e u (t)), quarantined exposed (e q (t)), symptomatically-infectious (i u (t)), asymptomatically-infectious (i a (t)), hospitalized/isolated (i h (t)), intensive care patients (i icu (t)) and recovered (r(t)), so that quarantine and isolation can either be at home (self-quarantine and self-isolation) or at designated healthcare facilities. furthermore, hospitalization in the context of this study includes self-isolation at home and isolation at the hospital (hence, hospitalization and isolation will be used interchangeably in this study). the model is given by the following deterministic system of nonlinear differential equations (where a dot represents differentiation with respect to time). where the force of infection λ is defined as: where β is the effective contact rate (i.e., contacts capable of leading to covid- transmission), < c m ≤ is the proportion of members of the public who wear face-masks (correctly and consistently) in public and < m ≤ is the efficacy of the face-masks (low values of c m imply limited use of face-masks by members of the public, while values of c m that are closer to unity imply widespread/universal use of face-masks in the community). furthermore, values of m that are closer to zero imply that the face-masks are not very effective in preventing acquisition (if worn by a susceptible human) or transmitting infection (if worn by a symptomatic or asymptomatically-infectious human), while m close, or equal to, unity implies that the face-masks used by the members of the public are of near or perfect efficacy against the acquisition or transmission of infection. reduction in the contact rate parameter (β) can be thought of a measure of effectiveness of strategies that limit contacts between people (to avoid community transmission), notably social (or physical) distancing. the parameter < η a < measures the relative infectiousness of asymptomatically-infectious humans (in the i a class) in relation to symptomatic individuals (in the i u class). similarly, < η h < is a modification parameter accounting for the relative infectiousness of hospitalized/isolated infectious humans (in the i h class) in relation to individuals in the i u class. the parameter < θ q ≤ is a measure of the effectiveness of quarantine, hospitalization/isolation and icu admission to prevent infected quarantined, hospitalized/isolated individuals and icu patients from transmitting infection. in particular, θ q = implies that infected quarantined, hospitalized/isolated individuals and icu patients mix freely with the rest of population and can transmit at the same rate as other infectious individuals. on the other hand, θ q = implies that the efficacy of quarantine, hospitalization/isolation and icu admission (in preventing infected quarantined, hospitalized/isolated individuals and icu patients from transmitting infection) is perfect. in other words, θ q = means infected quarantined, hospitalized/isolated infectious humans and icu patients are no longer part of the actively-mixing population (hence, do not contribute to disease transmission). in the model ( . ), the parameter < p ≤ is the probability of infection per contact, while q is the proportion of non-quarantined individuals that are infected at the time of quarantine. the parameter ψ q measures the rate at which quarantined-susceptible individuals revert to the wholly-susceptible non-quarantined class (s u ) at the end of the quarantine period. the modification parameter ≤ θ j ≤ is a measure of the efficacy of quarantine to prevent the acquisition of infection by quarantined-susceptible individuals (during quarantine). the parameters σ u (σ q ) is the rate at which exposed non-quarantined (quarantined) individuals progress to the symptomatic (hospitalized) class (i.e., /σ u and /σ q is the intrinsic incubation period of non-quarantined and quarantined exposed individuals, respectively). a proportion, f , of exposed individuals move to the i u class at the end of the incubation period (at the rate f σ u ). similarly, another proportion, f , moves to i h class (at the rate f σ u , and the remaining proportion, −(f +f ) moves to the i a class (at the rate [ −(f +f )]σ u ; noting that f +f < ). the parameter σ a represents the rate at which asymptomatically-infectious humans are detected (via contact-tracing) and hospitalized. the parameter σ a represents the rate at which asymptomatically-infectious humans are detected (via contact-tracing) and hospitalized. a proportion, r, of exposed quarantined individuals move to the i h class at the end of the incubation period (at a rate rσ q ), while the remaining proportion, − r, moves to the i a class (at a rate ( − r)σ q ). the parameter α u represents the rate at which exposed non-quarantined individuals are detected (by contacttracing) and placed in quarantine. the parameter γ u (γ a )(γ h )(γ icu ) is the recovery rate for individuals in the i u (i a )(i h )(i icu ) class, while ν h is the rate at which hospitalized individuals are placed into icu. furthermore, the parameter δ u (δ a )(δ h )(δ icu ) represents the covid-induced mortality for individuals in the i u (i a )(i h )(i icu ) class. the model ( . ) is an extension of the quarantine model for ebola viral disease developed by denes and gumel [ ] (by adding epidemiological compartments for asymptomatically-infectious humans and hospitalized individuals in icu, as well as incorporating contact-tracing of suspected cases and the use of face-masks by members of the general public). to the authors' knowledge, this may be the first deterministic model for covid- that incorporates five non-pharmaceutical interventions (quarantine, isolation, contact-tracing, use of public masks, and social-distancing), in addition to allowing for the assessment of the impact of asymptomatic transmission on the trajectory and burden of covid- (by adding a compartment for asymptomatic-infectious humans). a flow diagram of the model is depicted in figure , and the state variables and parameters of the model are tabulated in tables and ) . to keep track of covid- related deaths (required for calibrating our model with cumulative death data for covid- , and for quantifying and predicting the public health impact/burden of disease), we define the bookkeeping state variable d(t) to measure the number of covid-deceased individuals. it then follows from some of the equations of the model ( . ) that the rate of change of the population of deceased-individuals is given by: ( . ) we estimated the baseline epidemiological parameters of the model from available covid- data and sources from the published literature. since the generally recommended period for quarantine of people suspected of being exposed to covid- is days [ , ] , we set the rate at which quarantined susceptible individuals revert to the non-quarantined susceptible class (ψ q ) to be ψ q = / per day. further, whiel some studies have estimated the incubation period for covid- to range from - days, with about . % of infected people developing disease symptoms within . days of infection [ ] [ ] [ ] , other studies have estimated the incubation period to be - days [ ] . we consider an average incubation period (taken from these ranges) of . days, so that σ u = σ q = / . per day [ ] . similarly, we set the progression rate from the asymptomatically-infectious class (i a ) to the isolated/hospitalized class (i h )to be σ a = / per day. following [ , ] , we consider an infectious period of about days, so that the recovery rate from covid- infection (γ) is set to γ u = γ icu = / per day. ferguson et al. [ ] estimated the average time covid- patients spent in hospital (for infections that do not lead to complications requiring icu admission) to be about days. therefore, we set γ h = / per day. furthermore, [ ] , it is assumed that there is a short time lag (of about days) between the onset of disease symptoms in non-quarantined humans and hospitalization. hence, we set the hospitalization rate (φ u ) to be φ u = / per day. some studies have suggested that most covid- infections (over %) show mild or no symptoms, about % show severe symptoms (but without requiring icu admission), and % show criticallysevere symptoms requiring icu admission [ , , ] . consequently, we set f = . and assume that half of the % of cases that show no or mild symptoms are asymptomatic (hence, we set the modification parameter for the relative infectiousness of asymptomatic people (η a ) was estimated from [ , ] to be . . further, li et al. [ ] estimated this parameter to be between . and . . hence, we set η a = η h = . . since about % of covid- patients die [ ] , we estimated δ u = δ h = . per day. to obtain estimates for δ a and δ icu , we assume that δ a = . δ u (so that δ a = . per day) and δ icu = . δ u (so that, δ icu = . per day) [ ] . the parameter for the efficacy of quarantine to prevent acquisition of infection during quarantine (θ j ) is estimated to be θ j = . . we estimated the efficacy of face-masks ( m ) based on the results of a number of clinical trials. for instance, data from driessche et al. [ ] shows that surgical masks reduced p. aeruginosa infected aerosols produced by coughing by over % in cystic fibrosis patients. a similar study by stockwell et al. [ ] shows that surgical masks reduced colony-forming unit (cfu) count by over % (these two studies in [ , ] show that the n masks (respirators) were more effective). similarly, van der sande et al. [ ] show that home-made tea-cloth masks had an inward efficiency between % and % over a -hour duration of wear, while inward efficiency ranged . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . probability of infection per contact q proportion of infected humans quarantined at time of exposure ψ q rate at which quarantined individuals revert to the susceptible class ( /ψ q is the average duration in quarantine). modification parameter for the assumed reduced infectiousness of asymptomatically- efficacy of quarantine to prevent acquisition of infection during quarantine ( ≤ θ j < ). incubation period for non-quarantined (quarantined) exposed individuals σ a rate at which asymptomatically-infectious humans are detected (via contact-tracing) and hospitalized/isolated α u rate at which exposed non-quarantined individuals are detected (via contact-tracing) and placed in quarantine proportion of exposed non-quarantined individuals who progress to the i u (i h ) class at the end of the incubation period ( proportion of exposed non-quarantined individuals who progress to the i a class hospitalization rate of non-quarantined infectious individuals r( − r) proportion of exposed quarantined individuals who are hospitalized (not hospitalized) at the end of the incubation period, (i.e., move to the i h (i a ) class) θ q efficacy of quarantine, hospitalization/isolation and icu admission to prevent infected individuals in quarantine, hospital/isolation and icu from transmitting infection ( ≤ θ q ≤ ) - % and - % for surgical and n -equivalent masks. consequently, following eikenberry et al. [ ] , we estimate inward mask efficacy to range widely between - % for cloth masks, and at least % for well-made, tightly fitting masks made of optimal materials, and - % for surgical masks, and over % typical for p in the range of properly worn n masks. based on this, we set m = . . we set the proportion of quarantined exposed individuals who are hospitalized (r) to be r = . . there is no good data for the efficacy of isolation/hospitalization to prevent disease transmission by symptomatic individuals in isolation/hospital. nonetheless, it seems plausible to assume that, at the later stage of the pandemic (such as at the present moment), the public health system capacity has been greatly improved to the extent that such transmission do not occur. hence, we set θ q = . the parameter (ν h ) for the rate of icu admission is estimated to be ν h = . per day (based on data from [ ] it is in the range of % − %). the remaining parameters of the model ( . ), β, c m , σ a and α u , were estimated from the mortality data for the state of new york and the entire us [ ] [ ] [ ] [ ] (based on the fitting of the state of new york data in figure (a) and data for the entire us in figure (b)). the estimating process involved minimizing the sum of the squares of the difference between the predictions of model ( . ) (cumulative deaths) and the observed covid- cumulative deaths data from new york state (for the period from march , to april , ). in particular, the fitted values obtained using the state of new york mortality data were β = . per day, p = . per day, c m = . , σ a = . per day and α u = . per day, while the fitted values obtained using mortality data for the entire us were β = . per day, p = . per day, c m = . , σ a = . per day and α u = . per day. . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. [ ] [ ] [ ] [ ] . the red dots represent data points, while the solid blue line represent predictions of death from system ( . ). the asymptotic stability of the disease-free equilibrium of the model ( . ), given by , , , , , , , , ), will be analysed using the next generation operator method [ , ] . using the notation in [ ] , it follows that the next generation operator matrices, f and v for the new infection terms and the transition terms, are given, respectively, by it is convenient to define r c by (where ρ now represents the spectral radius of the next generation matrix f v − ): the result below follows from theorem of [ ] . the quantity r c is the control reproduction number of the model . . it measures the average number of new covid- infections generated by an average infected individual introduced into a population where basic public health interventions (quarantine, isolation, social-distancing, testing etc.) are implemented. the quantity r c is the sum of the constituent reproduction numbers associated with the number of new covid- cases generated by symptomatically-infectious humans (r ciu ), hospitalized/isolated individuals (r h ) and asymptomaticallyinfectious humans (r a ). the epidemiological implication of theorem . is that a small influx of covid- cases will not generate a covid- outbreak if the control reproduction number (r c ) is less than unity. for effective control of covid- to be independent of the initial sizes of the infected compartments of the model ( . ), a global asymptotic stability result must be established for the dfe. this is done below, for a special case. we claim the following result: theorem . . the disease-free equilibrium of the special case of the model ( . ) with θ j = (i.e., infected individuals in quarantine, hospital or icu do not transmit infection), is globally-asymptotically stable if r c ≤ . the proof of theorem . , based on using lyapunov function theory, is given in appendix a. the epidemiological implication of theorem . is that, for the special case of the model ( . ) with θ j = , bringing (and maintaining) r c to a value less than unity is necessary and sufficient for the effective control of the disease. it should be mentioned that if the assumption of θ j = is relaxed in theorem . , the proof will not work since the model will then undergo the phenomenon of backward bifurcation [ , ] . the baseline values of the parameters of the model are tabulated in table . we simulated the model ( . ) using the baseline parameter values tabulated in table (unless otherwise stated), to assess the population-level impact of the various control and mitigation strategies against the spread of covid- in the us state of new york discussed in section . . we also simulated the model using the calibrated parameters in table , together with the other estimated parameters in table , to assess the population-level impact of various control measures in the entire us. it should be mentioned that in all the simulations carried out, the various nonpharmaceutical interventions are maintained at their baseline values (unless otherwise stated). we simulated the model to, first of all, assess the impact of social-distancing (which, in our study, extends beyond individuals staying meters (or feet) apart to include school and non-essential business closures, staying at home, avoiding large gatherings, etc). further, in our study, we measured the effect of social-distancing by the overall reduction in the baseline value of the community contact rate parameter (β). the simulation results . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . obtained, depicted in figure , show a projected , patients in hospital (or in self isolation) at the pandemic peak, expected to be attained on may , (figure (a) ) and , cumulative number of deaths (figure (c) ) for the state of new york under the baseline scenario (i.e., for the baseline level of social-distancing). similarly, the projections for the entire us, under the baseline nation-wide social-distancing scenario, are , daily hospitalizations at the pandemic peak (figure (b) ) and , cumulative number of deaths (figure (d) ). it is noteworthy that our projection for the cumulative mortality for the entire us (of , ) falls markedly below the . million mortality projected by ferguson et al. [ ] . our us-wide mortality projection, however, falls within the range of ( , , , ) estimated by murray et al. [ ] . when social-distancing is improved above the baseline effectiveness levels (i.e., increase in efficacy and adherence/coverage of social-distancing), figure shows a dramatic reduction of covid- burden for both new york state and the entire us. in particular, for a social-distancing regimen that reduces the contact rate parameter β by % from its baseline value, the expected number of daily hospitalizations/isolation of confirmed cases at the peak of the pandemic decreases to , (corresponding to a % decrease in hospitalizations/isolation from baseline) for the state of new york. similarly, nation-wide hospitalizations/isolation of confirmed cases at the peak of the pandemic decreases by % to , . furthermore, for a highly-effective social-distancing strategy (such as a social-distancing strategy that results in at least % reduction in the baseline value of β), the peak hospitalizations/isolation of confirmed cases for new york state and the entire us dramatically reduce to , and , , respectively. similarly, for this scenario, the cumulative mortality for new york state and the entire us reduce, respectively, to , and , . thus, implementing a highly-effective social-distancing strategy (which can reduce the baseline community contact rate, β, by at least %) will avert over % and % of the predicted baseline deaths in new york state and nationwide, respectively. the effectiveness levels and coverage of social-distancing in new york state and the entire us has greatly improved, by april , [ ] [ ] [ ] [ ] , to the extent that it is plausible to assume that % reduction in the baseline value of β has already been achieved in both the state of new york and nationwide. therefore, this study shows that the state of new york and the entire us could have recorded catastrophic covid-induced mortality (between , to , ) if not for the high effectiveness levels and coverage of the strict social-distancing measures implemented in the state and nationwide. our study suggests that if the current level of social-distancing effectiveness and coverage is maintained through may or june , in the state of new york and nationwide, covid- can be eliminated from both the state and the entire nation. extending the simulations for figure shows that the current level of the social-distancing regimen in the state of new york should be extended until late september to guarantee the elimination of covid- (in the context of figure , covid- elimination is measured in terms of when the cumulative mortality stabilizes). similarly, for the entire us, social-distancing needs to be maintained until march . additional simulations were carried out to assess the population-level impact of the duration and timing of when to terminate the current strict social-distancing protocols. for the best-case scenario, where the current strict socialdistancing protocols were assumed to be implemented right from the very beginning of the covid- pandemic in new york state (march , ) and the entire us (january , ) and maintained until early december, , the results obtained for the cumulative mortality recorded for new york state and the entire us are , and , , respectively (blue curves in figure (a)-(f)). furthermore, if the social-distancing regimens were implemented on the days they were officially implemented in new york state (march , ) and the entire us (march , ), but maintained until early december, , the cumulative mortality to be recorded will be , and , , respectively (magenta curves in figure (a)-(f)). the effect of the timing of when to terminate the current strict social-distancing protocols was also monitored. our simulations show that terminating the current strict social-distancing by the end of april (i.e., the % reduction in the baseline value of β is now lost due to the termination of the social-distancing measures), a significant rebound of covid- burden will be recorded in as early as july . in particular, new york state will record , deaths ( (a)), while the entire us will record up to , deaths ( (d)). in other words, the early termination of the current strict social-distancing measures (by the end of april ) will result in catastrophic covid- burden, similar to the dire projections made for the pre-social-distancing period (i.e., all the gains of the social-distancing and other control and mitigation measures will essentially be lost). if the strict-distancing measures were to be terminated by the end of may, , the cumulative mortality figures are projected to be , for new york state and , for the entire us ( . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint (b) and (e)). finally, if the social-distancing measures are terminated at the end of june, , the projection for the mortality figures are , for new york state and , for the entire us ( (c) and (f)). these projected mortality numbers, for the early termination of social-distancing, fall within the range given by murphy et al. [ ] . our study clearly shows that the clamor to relax or terminate the social-distancing measures (that have proven to be hugely successful in both the state of new york and the entire us), as part of the move to re-open the state and the country, would undoubtedly trigger a devastating rebound of covid- in both new york state and the entire us. data has already shown that certain countries that have relaxed the successfully-implemented social-distancing measures, such as taiwan, hong kong and south korea, are now witnessing a rebound of covid- [ ] . in particular, hong kong announced newly-confirmed cases on march (followed by over new daily cases in the next three days). further, taiwan reported more than newly-confirmed cases per day in mid-march (up from barely cases per day late in january). south korea reported newly-confirmed cases on april , [ ] . it is worth mentioning that the aforementioned simulations for the effect of social-distancing were carried out for the case where other interventions (contact-tracing, quarantine, face-mask, usage etc.) are also implemented (at their baseline values in tables and ). if face-masks are not used, then the above cumulative numbers will be even more catastrophic. for instance, if the strict social-distancing protocol is terminated in new york state by april , , and no face-mask-based intervention is implemented, about , deaths will be recorded by july . furthermore, terminating the social-distancing protocols by end of may or end of june will result in projected , and , deaths, respectively, in the state. the corresponding numbers for the entire us (for the case where mask-based intervention is not implemented) are projected to be , , , , and , , respectively. thus, this study strongly suggest that utmost caution should be exercised before terminating the current strict social-distancing protocols being implemented in the state of new york and nationwide. at the very least, a careful state-by-state (or county-by-county) phase withdrawal (based on the updated covid- incidence, mass testing data, and proximity to covid- hot spots) should be carried out. the effect of quarantine of individuals suspected of being exposed to covid- is monitored by simulating the model ( . ) using the baseline parameter values and various levels of effectiveness of quarantine to prevent the acquisition of infection during quarantine (θ j ). the results obtained, depicted in figure , show that quarantine of susceptible individuals has only marginal impact in reducing covid-related hospitalizations for both new york state ( figure (a) ) and the entire us ( figure (b) ). in particular, at the baseline quarantine efficacy (θ j = . ), the state of new york will record , daily hospitalizations. the implementation of a perfect quarantine in the state (i.e., θ j = ) reduces the number of hospitalizations marginally to , . the numbers for the entire us for the baseline and perfect quarantine are , and , , respectively. the marginal effect of quarantine in minimizing covid-related hospitalizations is even more pronounced when the isolation strategy is perfect ( figures (c) and (d) ). that is, for the epidemiological scenario where the isolation (or hospitalization) of confirmed cases is perfect (that is, individuals in isolation at home or in hospital are not part of the actively-mixing population, so that θ q = ), the community-wide implementation of mass quarantine of individuals suspected of being exposed to covid- will have very marginal impact on covid- burden (measured in terms of reductions in covid- hospitalizations). this result is consistent with that reported in [ ] . thus, this study suggests that, since selfisolation and isolation in hospitals have been implemented at high effectiveness levels in both the state of new york and in the entire us, the mass quarantine of suspected cases may not be a cost-effective public health strategy for combating the spread of covid- in both new york state and the entire us. figures (c) and (d) illustrate the dynamics of the model ( . ) for various effectiveness levels of quarantine and isolation, for both new york state and the us, further emphasizing the marginal nature of quarantine (even for the cases where isolation was not implemented at a perfect level) in minimizing covid- hospitalizations. the effect of contact-tracing on the transmission dynamics and control of the covid- pandemic is also monitored by simulating the model ( . ) using the baseline parameter values in table and various values of the contact-tracing parameters (α u and σ a ). in particular, the simulations are run by increasing the values of α u and σ a , simultaneously (and by the same amount) from their respective baseline values. figure depicts the solution profiles obtained, showing the worst case scenario of , cases in the state of new york and , cases nationwide on the day the pandemic peaks (on april , ) if no contact tracing is implemented. if implemented at its baseline rate, contact tracing reduces the size of the pandemic peak number of new covid- cases by % . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . for the state of new york, and by % nationwide, while a % improvement in contact-tracing will reduce the predicted number of confirmed cases to approximately , for the state of new york and , nationwide. this represents % and % reduction from baseline and shows that while contact-tracing implemented even only at baseline is important in reducing the size of the pandemic peak number of new covid- cases, investing much resources towards contact-tracing beyond the baseline rate might not be cost-effective. simulations were further carried out to assess the population-level impact of the widespread use of masks in public, by running the model ( . ) with various values of mask efficacy ( m ) and coverage (c m ). the results obtained, depicted in figure , show a marked decrease in the number of hospitalizations, for both new york state (figures (a), (b) and (c) ) and the entire us (figures (d) , (e) and (f)), with increasing values of the mask efficacy and coverage. further, using an efficacious mask, such as a mask of efficacy %, can greatly flatten the pandemic curve, in addition to significantly reducing the burden of the pandemic (measured, in this case, in terms of hospitalizations). however, such a mask will fail to lead to the elimination of the disease (figure (b) ). it is worth emphasizing that, although the use of masks with low efficacy may not lead to disease elimination, they still are highly useful by causing a significant decrease in the burden of the pandemic (i.e., significantly reduce hospitalizations) if a significant proportion of the populace wear them. for instance, if % of the populace in new york or the entire us wear masks with efficacy as low as % (i.e., cloths masks), the number of hospitalizations will be reduced by % and %, respectively (compared to the scenario were masks were not used) (figures (a) and (d)). a contour plot of the reproduction number of the model (r c ), as a function of masks efficacy ( m ) and compliance (c m ) for the special case of the model with θ j = , is depicted in figure . it should be noted from theorem . that, for the special case of the model with perfect quarantine (i.e., θ j = ), the disease-free equilibrium is globally-asymptotically stable whenever r c < (i.e., the disease can be eliminated from new york state if r c < ). this result is further illustrated in the contours plot depicted in figure (a) and (b) . however, if masks of higher efficacy, such as surgical masks (with estimated efficacy ≥ %) are used in the state, disease elimination is, indeed, feasible if at least % of the populace wear the masks (figures (a) and (b) ). similar results were obtained for the entire us (figures (c) and (d) ). additional simulations were carried out to assess the combined impact of public face-masks use strategy and strict social-distancing strategy (which reduces the baseline value of the community transmission parameter, β, by %) on the control of covid- in new york state and the entire us. the results obtained, depicted in figure , show that, combining the strict social-distancing strategy with a strategy based on using moderately-effective face-masks (with efficacy m ≥ . ) in public, will lead to the elimination of the disease in new york state if only % of the population use face-masks in public (figure (a) ). this clearly shows that disease elimination in new york state is more feasible if the face-masks-based strategy is combined with the strict social-distancing strategy. similar results were obtained for the entire us (figure (b)), where, in this case, only % compliance in mask usage in public will be needed for covid- elimination. in summary, the above simulations show that the use of face-masks (even those with low efficacy, but with high coverage) in public offers significant community-wide impact in reducing and mitigating the burden of covid- in both new york state and the entire us. in other words, the use of low efficacy face masks with high coverage is always useful. further, combining the face-masks use strategy with a strategy based on the implementation of strict social-distancing is more effective in curtailing (and eliminating) covid- , in comparison to the singular implementation of either strategy. . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. tables and , with various values of β. . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. tables and , with various values of θ j and θ q . . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . the world is currently experiencing a devastating pandemic of a novel coronavirus (caused by sars-cov ) that emerged in wuhan city of china in december of . the deadly covid- pandemic has spread to over countries, causing over . million cases and , deaths worldwide (with some parts of asia, europe and, now, the us suffering the brunt of the burden). there is currently no safe and effective vaccine for use in humans against covid- . there is also no safe and effective antiviral. consequently, control and mitigation efforts against covid- are limited to non-pharmaceutical interventions, such as social-distancing (which involves keeping a physical distance of at least feet from other humans in public, lockdowns of communities, closure of schools, malls, places of worships and other gathering places), quarantine of suspected cases, contact-tracing, isolation (at home or in hospital) of confirmed cases and the use of face masks (both low quality cloth masks and the higher quality surgical masks) in public. this study is based on the design, analysis and simulations of a new mathematical model for providing deeper insights into the transmission dynamics and control of covid- in a community. specifically, the model designed in this study was parametrized using covid- data from the us state of new york and the entire us population. the model was used to assess the population-impact of the aforementioned control and mitigation interventions. the model was rigorously analysed to gain insight into its dynamical features. it was shown that the diseasefree equilibrium of the model is locally-asymptotically stable when a certain epidemiological threshold, known as the reproduction number (and denoted by r c ) is less than unity. the epidemiological implication of this result is that a small influx of covid- cases will not generate a large outbreak in the community if r c is less than unity (and the disease can be effectively controlled in this case). for such effective control (or elimination) of the disease to be independent of the initial sizes of the infected population, a global asymptotic stability must be established for the disease-free equilibrium. this was done for the special case of the model where quarantine is perfect (i.e., the special case of the model where quarantined-susceptible individuals do not acquire infection during quarantine). the implication of this theoretical result is that, for the case where quarantine of susceptible individuals is perfectly implemented in the community, the aforementioned control and mitigation strategies can lead to the elimination of the covid- pandemic if their effectiveness levels (measured in terms of their efficacy and coverage) are high enough to bring (and maintain) the associated reproduction number of the model to a value less than unity. the epidemiological meaning of elimination is the cessation of community transmission. our study shows that covid- elimination in the state of new york and the entire us is feasible using the basic non-pharmaceutical . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . interventions discussed in this study (notably social-distancing, use of face-masks in public and contact-tracing and quarantine) if implemented at the required level of effectiveness and compliance/adherence. thus, this study shows that covid- elimination can be considered a realistic goal in the us. if achieved, sustaining such elimination would require taking further measures to minimize the possibility of a rebound, such as more consistent surveillance for covid- , the potential use of a vaccine and expanded testing. we parameterized the model using covid- data from new york state and the entire us, and extensive numerical simulations were carried out using the parametrized model to assess the population-level impact of the various intervention strategies. with the baseline levels of the four main intervention strategies considered (socialdistancing, quarantine/isolation, contact-tracing and the use of face-masks), the state of new york is projected to see a peak of the pandemic around mid april, (with , number of hospitalizations/isolation of confirmed cases and , deaths at the peak), while the entire us will see its peak around end of april, (with , hospitalizations/isolation of confirmed cases and , deaths at the peak). our projections for baseline (worst-case) mortality for the us are much lower than the . million deaths suggested by ferguson et al. in the absence of interventions [ ] , but fall within the range estimated in [ ] . our projected numbers for covid- burden (morbidity and mortality) dramatically decreases if strict social-distancing measures are implemented at high adherence levels. for instance, it was shown that strict compliance to the statewide lock-down in new york state (which corresponds to reducing the baseline contact rate in our model by at least %) will reduce the peak values for hospitalizations/isolation of confirmed cases and mortality to , and , , respectively. similarly, the peak values for cases and mortality in the entire us (if a nation-wide lockdown capable of reducing baseline contact rate by at least %) will decrease to , and , , respectively. the duration and timing of the termination of strict social-distancing measures are critically-important in the battle to effectively combat pandemics of respiratory diseases, such as the devastating covid- pandemic. while the rapid implementation of strict social-distancing measures (during the early stage of the pandemic), maintained over a relatively long period of time (e.g., until the summer), will undoubtedly effectively combat the burden of the pandemic. early termination of these measures will cause catastrophic outcomes. for instance, our study shows that relaxing or terminating the strict social-distancing measures in the state of new york and the us as a whole by end of april will trigger a devastating second wave, generating covid- burden similar to those obtained during the pre-strict-social-distancing time in the state and in the entire nation by the end of july (with cumulative mortality numbers in the range reported in [ ] for both new york state and the entire us). in particular, up to , and , cumulative deaths will have been recorded in the state of new york and the entire us if the social-distancing measures are shut down by the end of april, . extending the termination of social-distancing, such as to end of june , significantly reduces the likelihood of a second wave (in addition to significantly reducing the associated burden of the pandemic). consequently, a great deal of caution must be exercised before decisions are made to relax or terminate the existing highly-successful social-distancing protocols in both the state of new york and the entire us. it is noteworthy that countries that have recently relaxed these measures, such as taiwan, hong kong and south korea, have already started seeing a rebound of covid- . our study suggests that the decision to relax or terminate the social-distancing measures should by on a case-bycase (i.e., state-by-state or county-by-county) basis, and should be informed by updated covid- incidence and mortality data, number of covid- tests (both antibody and surveillance tests) and proximity of a locality to covid- hot spots. in particular, our study shows that strict social-distancing should be maintained until the year (up to late september for new york state, and early march, for the entire us) to eliminate covid- . quarantine of people suspected of being exposed to a respiratory disease is perhaps the oldest public health control measure in human history. our study shows that widescale implementation of quarantine intervention may not be very effective (in minimizing the burden of covid- ) if the strategy of isolating confirmed cases is effective. in other words, our study suggests that if isolation can be implemented effectively (high efficacy and coverage), then quarantine of people suspected of contracting covid- may not be necessary. this result is consistent with what was reported by day et al. [ ] . tracing the contacts of confirmed cases (known as contacttracing) was also shown to only be marginally-effective in minimizing the burden of the pandemic. in particular, even if contact-tracing is implemented at the highest possible level (represented in our study based on increases in the contact-tracing parameters by %), the decrease in the burden of the pandemic recorded was only marginal ( % and % for cases in new york state and nationwide, respectively, and % and % for mortality for new york state and nationwide, respectively). the use of face-masks in public in times of outbreaks of respiratory diseases has a rich history. although quite popular in some parts of the world (notably asia), the use of face-masks in public is somewhat controversial. this was more evident in the us during the covid- , leading, ultimately, to the recommendation to use face-masks (home-made cloths masks) in public by the the us centers for disease control and prevention (cdc) on april , . our study shows that the use of high efficacy masks (such as surgical masks, with estimated efficacy of at least %) will lead to a dramatic reduction of covid- burden if its coverage is high enough (at least %). in fact, our study shows that even face-masks of low efficacy (home-made cloths masks) will lead to a dramatic reduction of disease burden (albeit this will not lead to the elimination of the disease). for example, even face-mask efficacy of % can lead to a % and % reduction in the number of hospitalizations/isolation of confirmed cases at the pandemic peak in new york state and nationwide if % of the population wear face-masks in public. these results are consistent with those reported by eikenberry et al. [ ] . furthermore, by generating contour plots for the control reproduction number of the model ( . ) (r c ), as a function of mask efficiency ( m ) and coverage (c m ), our study shows that the use of high efficacy masks (such as surgical masks, with estimated efficacy of ≥ %) will, indeed, lead to the elimination of covid- (in both the state of new york and in the entire us nation) if the coverage is high enough (about %). this study shows that the use of face-masks in public is always useful, and their population-level impact increases will increases efficacy and coverage. in particular, even the use of low efficacy masks will greatly reduce the burden of the pandemic if the coverage in their usage in the community is high enough. furthermore, our study shows that combining the masks-based strategy with the strict social-distancing strategy is more effective than the singular implementation of either strategy. for instance, our study shows that covid- can be eliminated from the state of new york if the strict social-distancing measures implemented are combined with a face-masks strategy, using a moderately-effective mask (with efficacy of about %) if only % of the residents of the state wear the masks. the masks use compliance needed to eliminate the disease nationwide, under this scenario with strict social-distancing nationwide, is a mere %. in summary, our study suggests that, like in the case of the other coronaviruses we have seen in the past (namely sars and mers [ ] ), covid- is a disease that appears to be controllable using basic non-pharmaceutical interventions, particularly social-distancing and the use of face-masks in public (especially when implemented in combinations). the factors that are obviously critically-important to the success of the anti-covid- control efforts are the early implementation (and enhancement of effectiveness) of these intervention measures, and ensuring their high adherence/coverage in the community. . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint proof. consider the special case of the model ( . ) with θ j = . further, consider the following linear lyapunov function: l = g e u + g e q + g i u + g i h + g i a , where, g = {[g α u +g σ u +g f σ u +g ( −f −f )σ u ]}/k , g = [rg +( −r)g ], g = k k k +g φ u , g = k k k η h and g = η a k k k + k k k η h σ a . it follows that the lyapunov derivative is given by: l = g Ėu + g Ėq + g İu + g İh + g İa , + g [f σ u e u + rσ q e q + φ u i u + σ a i a − k i h ] which can be simplified to, so that (noting that s u (t) ≤ [n − θ q (e q + i h + i icu )](t) for all t), . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint ≤ i= k i i u + η h i h + η a i a (r c − ) . hence,l < if and only if r c < , andl = if and only if e u = e q = i u = i h = i u = . therefore, l is a lyapunov function for system ( . ). hence, it follows by the lasalle's invariance principle, that the dfe of the special case of the model ( . ) with θ j = is globally-asymptotically stable whenever r c ≤ . . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ 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us state in the next months statistical evidence social distancing is working: look at the effect on new coronavirus cases over time new york reports more deaths, governor says social distancing working, reuters: heath news (assessed on new york governor cuomo says social distancing efforts are working to slow coronavirus, cable news network (cnn) (assessed on social distancing is controlling covid- ; now scientists need to figure out which measures are most effective, stat (health) (assessed on the asian countries that beat covid- have to do it again, wired (accessed on when is quarantine a useful control strategy for emerging infectious diseases? one of the authors (abg) acknowledge the support, in part, of the simons foundation (award # ) and the national science foundation (award # ). cnn acknowledges the support of the simons foundation (award # ). one of the authors (abg) acknowledges the useful conversation with dieter armbruster on some aspects of public mask usage. appendix a: proof of theorem . key: cord- -yao v authors: carneiro, carlos b.; ferreira, i'uri h.; medeiros, marcelo c.; pires, henrique f.; zilberman, eduardo title: lockdown effects in us states: an artificial counterfactual approach date: - - journal: nan doi: nan sha: doc_id: cord_uid: yao v we adopt an artificial counterfactual approach to assess the impact of lockdowns on the short-run evolution of the number of cases and deaths in some us states. to do so, we explore the different timing in which us states adopted lockdown policies, and divide them among treated and control groups. for each treated state, we construct an artificial counterfactual. on average, and in the very short-run, the counterfactual accumulated number of cases would be two times larger if lockdown policies were not implemented. the evolution of the covid- has been posing several challenges to policymakers. decisions have to be made in a timely fashion, without much undisputed evidence to support them. being a new disease, and despite the enormous research effort to understand it, estimates of the transmission, recovery and death rates remain uncertain. nevertheless, these are key pieces of information to assess potential pressures on the health system capacity, as well as the need of a lockdown policy and its intensity if implemented. not surprisingly, similar regions have implemented different strategies regarding lockdowns. the leading example in the media is the looser social distancing policy in sweden versus strict policies in its scandinavian peers. by informally comparing the evolution of the pandemics in sweden and denmark (or norway), many commentators argue that several covid- cases and deaths in sweden would be avoided in the short-run were a strict lockdown in place. aiming to provide a quantitative assessment on the short-run effects of lockdowns, this paper takes this exercise seriously in the context of us states. given that the timing us states adopted lockdown policies differs among them, we adopt techniques based on synthetic control (sc) approach of abadie and gardeazabal [ ] and abadie et al. [ ] to assess the impact of lockdowns on the short-run evolution of the number of cases and deaths in the treated us states. more specifically, we consider an extension of the original sc method called artificial counterfactual (arco) which was put forward by carvalho et al. [ ] . due to the nonstationary nature of the data, the correction of masini and medeiros [ ] is necessary. our results point to a substantial short-run taming of the cumulative number cases due to the adoption of lockdown policies. on average, for treated states, the counterfactual accumulated number of cases, according to the method adopted here, would be two times larger were lockdown policies not implemented. a key feature of our approach is that it is purely data-driven. in the beginning of the crisis, the majority of papers written by economists to evaluate the effectiveness of lockdowns relied on epidemiological models for analysis, including the most recent ones that incorporate behavioral responses. these models are hard to discipline quantitatively. many calibrated parameters remain uncertain, and models that incorporate behavioral responses need time to mature and agree on a reliable set of ingredients and moments to be matched. model-free approaches like ours or medeiros et al. [ ] should complement policy discussions or forecasting exercises based on those models, especially from a quantitative point of view. there are related papers using state or county level us data. at least one of them, , uses a synthetic control approach but it is restricted solely to california. other papers, such as brzezinski et al. [ ] , and sears et al. [ ] , use variations in the timing of statewide adoption of containment policies, and difference-in-differences models to document substantial reductions in mobility and improvements of health outcomes. the key identification assumption in these papers is that variations in the timing are random after controlling for covariates. brzezinski et al. [ ] also consider an instrumental-variable approach. fowler et al. [ ] and grassi and j. sauvagnat [ ] follow similar empirical strategies but at county level, and also find substantial reductions in cases and fatalities in counties that adopted stay-at-home orders and state-mandated business closures, respectively. our analysis, that rests on alternative identification assumption and method, should be seen as complementary. as the pandemic evolves, and more data become available, we expect more related empirical evidence to be consolidated. the paper is organized as follows. section describes the data, while section presents the empirical strategy. the results are discussed in section . finally, section concludes the paper. additional results are included in the appendix. data on covid- (confirmed) cases are obtained from the repository at the johns hopkins university center for systems science and engineering (jhu csse). we consider the cumulative cases for a subset of the us states and the district of columbia. instead of using the chronological time across the states, we consider the epidemiological time, which means that the day one in a given state is the day that the first covid- case was confirmed there. the econometric approach adopted here relies on the fact that some states adopted a lockdown strategy (the treatment), whereas others did not adopt social distancing measures (control group) and are used to construct the counterfactual. lockdown strategies include a mix of state-wide non-pharmaceutical measures aiming to limit social interactions, such as restrictions on nonessential activities and requirements that residents stay at home. containment policies. see, for example, atkeson [ a] on the uncertainty regarding estimates of the fatality rate. there are also related papers for other countries. for example, fang et al. [ ] for china. the timing of those policies at each state were obtained, and double checked, in several press articles, e.g., https://www.businessinsider.com/us-map-stay-at-home-orders-lockdowns- - and https://www.nytimes.com/interactive/ /us/coronavirus-stay-at-home-order.html. in this section, we describe how we assign states to control and treatment groups, and then, describe the method used to construct the counterfactuals. aiming to balance control and treatment states, and at the same time obtain enough observations to estimate properly the model before the lockdown policy was implemented, we divide us states into three groups. for a state to be included in the analysis, a state-wide lockdown policy must be established at least twenty days after the first case. we assume that whenever an individual becomes infected, it takes an average of ten days to show up as a confirmed case in the statistics. hence, the in-sample period used to estimate the synthetic control ("before" the lockdown policy) for each treated state (to be defined below) is the number of days between the tenth day after the first confirmed case and the tenth day after the lockdown strategy was implemented. we choose to start the in-sample from the tenth day as a way to smooth the initial volatility of the data. we adopt a criteria that a state must have at least twenty observations in the in-sample period to be included in the analysis. this criteria excludes states that adopted a state-wide lockdown strategy too early, such as connecticut, new jersey, ohio, among others. these are the unmarked states in table , which reports the dates of the first case and lockdown policy, as well the difference in days between them, and also helps visualize the three groups of states. the remaining states must be divided into treated and control groups. the idea is to find a synthetic control for each of the treated states. the group of potential controls should consist of states that adopted a lockdown policy too late (or never adopted), such that counterfactuals are not contaminated by lockdown policies implemented in those states. at the same time, and for a similar reasoning, the lockdown strategies adopted in treated states must be in place during the period of analysis. this assumption is motivated by the incubation period of the virus. according to the world health organization, the "[...] the incubation period for covid- , which is the time between exposure to the virus (becoming infected) and symptom onset, is on average - days, however can be up to days." see https://www.who.int/docs/default-source/coronaviruse/situation-reports/ -sitrep- -covid- .pdf. in the appendix a. , table a . shows the reopen dates for the treated states. fortunately, there are horizons that can balance both goals: enough states to build the synthetic controls and a relative extensive period to construct the counterfactuals. in particular, we restrict the analysis up to the th epidemiological day. this figure accommodates at least ten control states to build the synthetic controls, at the same time it maximizes the out-of-sample days to run the counterfactuals. in this sense, our analysis concerns the very short-run impact of lockdowns, up to nearly three weeks. the treated states are marked in blue in table , and include twenty states: alabama, colorado, florida, georgia, kansas, kentucky, maine, maryland, mississippi, missouri, nevada, new hampshire, new york, north carolina, oregon, pennsylvania, rhode island, south carolina, tennessee, and texas. the potential control states are marked in red, and include ten states: arizona, arkansas, california, illinois, iowa, massachusetts, nebraska, north dakota, south dakota, and washington. nonetheless, due to the lack of variation within the in-sample period, we exclude four states from this control pool as we explain below. importantly, oklahoma, utah and wyoming only implemented partial lockdowns (not reported in the table). therefore, they are hard to classify as either treated or control states. we opt to exclude them from the analysis. figure illustrates the empirical strategy, which is formalized in the next subsection. it plots the evolution of (log) cumulative cases along the epidemiological time. the first vertical dashed line represents the tenth day after the first confirmed case. the in-sample period is represented in between the first and second vertical dashed lines, which mark the tenth day and the following twenty days, respectively. similarly, the out-of-sample period is in between the second and third vertical dashed lines, which mark the th and th epidemiological day, respectively. blue lines represent the treated states, whereas the red ones the potential control states. the turning points from blue full-to dashed-lines represent the days lockdowns were implemented (plus ten days) in treated states. note that new york is clearly an outlier among the treated states, exhibiting a huge amount of cases (more on that below). we use the red lines to build synthetic controls for each full blue-line up to the turning point, and then construct counterfactuals by simulating the synthetic controls forward up to the th day. the idea is to compare them with the blue dashed-lines that capture actual cases. as figure highlights, some states display lack of variation within the in-sample period. just to give an example, washington had had only one confirmed case for the first days since its first confirmed covid- infection. hence, we exclude it from the control group. for similar reasons, we also exclude arizona, illinois, and massachusetts from the control pool. the analysis ended up relying on six control states. we propose a two-step approach using the artificial counterfactual (arco) method introduced by carvalho et al. [ ] with the correction of masini and medeiros [ ] to estimate the number of cases for each us state. let = , , . . . , represents the number of days after the first confirmed case of covid- in a given state. define as the natural logarithm of the number of confirmed cases days after the first case of the disease in this specific treated state, and as a vector containing the logarithm of the number of reported cases for control states also days after the first case has been reported as well as a logarithmic trend: log( ). the inclusion of the trend is important to capture the shape of the curve. the model is estimated as follows. we use the weighted least absolute and shrinkage operator (wlasso) as described in masini and medeiros [ ] to select the control states that will be used to estimate our counterfactual. the goal of the lasso is to balance the trade-off between bias and variance and is an useful tool to select the relevant peers in an environment with very few data points:̂︀ = arg min where = | , |, = , . . . , − , and = . is, for each state, the number of days from the first reported case until the lockdown plus ten extra days, and > is the penalty parameter which is selected by the bayesian information criterion (bic), in accordance with medeiros and mendes [ ] . the weight correction in the lasso is necessary in order to control for the nonstationarity of the data; see masini and medeiros [ ] for a detailed discussion. the counterfactual for = + , . . . , is computed aŝ︀ we also report % confidence intervals based on the resampling procedure proposed in masini and medeiros [ ] . we are interested in examining the effects of lockdown policies not only on the number of cases, but also on the number of deaths. however, we cannot implement the strategy described above because there is not enough variation in deaths for the in-sample period. some states, for instance, implemented a state-wide lockdown policies before the first confirmed death. thus, we propose an alternative method. we consider a counterfactual state for the number of deaths based on the counterfactual estimated for the number of cases. this is not straightforward as in the traditional synthetic control method because the arco methodology described above includes an intercept in the estimation, which is measured in the log of the number of cases, and not only a convex combination of other states. intuitively, the methodology described above chooses a combination of states that is at a fixed distance from the treated unit at the in-sample period and not a convex combination of states that matches exactly the actual number of cases. the intercept controls for all time-invariant characteristics that define the counterfactual. then, we proceed as follows. let be the number of accumulated deaths in state at the day . also, let be the vector of estimated coefficients for the state as in ( ) and used to construct the counterfactual for cases. in addition, let be a vector of the number of deaths for all states in the control pool at time . we define the counterfactual number of deaths in that state as: = −¯+¯ ( ) where¯is the day that state implemented the lockdown policies. that is, we maintain the weights estimated above and adjust the intercept so that the counterfactual series for deaths matches the number of actual observed deaths in the beginning of the quarantine. for the sake of exposition, we relegate the results on cumulative deaths to appendix a. . to illustrate how the method works, figure presents the arco counterfactuals for the states of alabama, colorado, and maine. the timing of the policy intervention ( + ) corresponds to the lockdown date plus ten days. the counterfactual analysis makes it clear the importance of lockdown policies in mitigating the acceleration of the number of covid- confirmed cases in the treated states. as shown in figure a , for example, our results point to a substantial increase in the number of cases in alabama if it had not adopted an early lockdown. similarly, figures b and c reveal the same behavior for the cumulative curves in the other selected states. counterfactuals are constructed with the estimated weights and cumulative cases of the six states that compose the control group. these weights are reported in table a . in appendix a. . in appendix a. , we present similar counterfactual plots for the remaining treated states. in order to assure that the proposed methodology is producing proper counterfactual analysis, we generate placebo results by producing a "synthetic control" for each control state using the remaining control states as control pool. results are displayed in figure , which shows the ratio of the estimated counterfactual cumulative cases to the actual ones for treated states except new york (black lines), and non-treated states (red lines). we assume that the epidemiological day of the placebo intervention is = , marked by the vertical dashed line, which is the median (and the mean) timing of the policy interventions in the treated states. it is reassuring that for half of the placebo counterfactuals the ratios fluctuate around one, whereas for the majority of treated states ratios grew above one at some point (likely around the actual timing of policy intervention). the latter result means that lockdown policies were effective to tame the spread of the virus, whereas the former suggests that results are not driven by chance. regarding south dakota, the only placebo counterfactual that reached a ratio well above one, by using google mobility data (described in appendix a. ), we show that mobility in residential areas increased whereas mobility in outdoor areas decreased substantially once compared to the period before the pandemic (see figures a. and a. in appendix a. ) . this is suggestive that south dakota's population endogenously decided to stay more at home, and avoided environments prone to the risk of contamination. at the time, a proper lockdown policy was not necessary, and south dakota's non-conformity to the placebo test does not seem to invalidate our approach. in contrast, for nebraska and california, the counterfactuals are pointing to a smaller number of cases than the actual ones, which goes against finding that lockdowns were effective to reduce cases of covid- . the case of california is quite emblematic, as the number of cases during the estimation window remained very small and with very low variation. however, the number of cases started to grow at a fast rate much after the cut-off date. the state of nebraska displays a similar pattern. to gauge the quantitative impact of lockdown policies, for each state, whether treated or control used as placebo, we compute the ratio of the counterfactual estimated comulative cases ("without" a lockdown strategy in place) to actual ones on the th epidemiological day, which is the last day used to compute the counterfactual. table reports the mean and median of the ratios across states, whereas table a . in appendix a. reports these ratios for each state. the first row corresponds the case in which controls are used as placebos, whereas the second considers the treated states only. as we discuss below, new york is clearly an outlier, whose ratio reached an implausible value of . as reported in table a . . hence, our preferred specification is displayed in the third row which excludes new york from the pool of treated states. we also compute other two versions of these ratios using the lower bound (lb) and upper bound (up) of the % confidence interval in the numerator. the ratios are clearly above one for the treated units, whether new york is excluded or not. according to our preferred specification, counterfactual estimates suggest that the number of cases would be nearly two times larger were lockdown policies absent. again, it is reassuring that among the controls used as placebo, these average ratios remain around one. regarding the effects of lockdowns on cumulative deaths, we present the results for all treated states in appendix a. . for some states, the counterfactual cumulative deaths exhibit similar patterns to those regarding cumulative cases. but, for many other states, they are not statistically significant at least for the first days after the policy implementation. one possible explanation is that there is a delay between cases and deaths, as the latter is a consequence of the former. hence, deaths only show up in the official statistics days after cases. perhaps, if we could estimate counterfactuals for longer periods, the synthetic accumulated deaths would further decouple from the actual ones. in addition, since weights on the controls are estimated considering the (log) cumulative number of cases, the counterfactuals for cumulative deaths are arguably noisier. as discussed above and presented in table a . in appendix a. , we obtain an implausible ratio (of counterfactuals to actual cumulative cases) of . to new york. this section puts a lens on this state. in particular, figure displays the estimated cumulative number of cases for new york "without" lockdown, as well as extrapolations of the cumulative number of cases based on the mean and median growth rate of the last ten days of the in-sample period. as reported in table , among the treated states, new york was the fastest one to react to the pandemic, and established a state-wide lockdown policy only days after the first case. figure extrapolates the last in-sample observations by using both the observed mean and median growth rates for the last ten days, which yields a similar pattern to the result obtained by applying the synthetic control approach. due to the progression of the virus, particularly in new york city, the in-sample observed rates are quite high once compared to other states as illustrated in figure , which can be explained not only by the dynamics of the city but also by its high population density. hence, new york is clearly an outlier and might not be amenable to our synthetic control approach, which justifies reporting results excluding new york above. in this paper, as opposed to most of the early and incipient literature on the lockdown effects during the covid- crisis, we conisder a purely data-driven approach to assess the impact of lockdowns on the short-run evolution of the number of cases and deaths in some us states. also, as opposed to some recent papers that use a difference-in-difference approach, we adopt a variant of the synthetic control approach, arco, due to carvalho et al. [ ] and masini and medeiros [ ] . on average, according to the synthetic controls, the counterfactual accumulated number of cases would be two times larger were lockdown policies not implemented in treated states. in the first two columns of table a . we show the date of the first confirmed case in every treated state we analyze and its reopen date (plus ten days), whenever available at the time we started to circulate this paper. in the third column, we show the difference (in days) from the first confirmed case and the reopen date plus ten days. these figures illustrate why we had to limit our sample size to only epidemiological days. for example, if we had used days in our analysis, we would have to exclude alabama and maine from our treated states, given that they would not be in a state-wide lockdown in the last days of the out-of-sample period. we report in the first seven rows of table a . the coefficients estimated by the lasso model for each treated state for the + in-sample period. the last two rows display the mean and the median (across the out-of-sample period) of the ratio between the actual cumulative cases and the counterfactual cases for every state. with only two exceptions (missouri and nevada), every state has an out-of-sample mean and median of the observed-to-predicted ratio below one. this means that, on average, the realized cumulative cases were smaller than the counterfactual, which highlight that lockdowns had a meaningful impact on slowing down the covid- spread in these states. table a . reports the ratio of the counterfactual cumulative cases to the actual ones on the th day after the first confirmed case in each state. it also reports the lower and upper limits of the % confidence interval. among the treated states, the ratio is larger than one in of them. for missouri and nevada, there is no evidence on the effectiveness of lockdown policies. for mississipi and south carolina, the impacts of lockdowns are only modest. note that new york is clearly an outlier, with such ratio around . . we discuss this case in the main text. in contrast, among the non-treated states, we obtain ratios close to one for three out of six cases. we assume that the cut-off of the placebo intervention is = , which is the median (and the mean) timing of the policy interventions in the treated states. as discussed in the main text, south dakota, which displays a ratio well above one, experienced a large reduction in outside mobility even without official lockdown measures. california and nebraska, which display ratios below one, had very few covid- confirmed cases during the period before the cut-off. in this section, in figures a. -a. , we report the counterfactual estimates for cumulative deaths based on the methodology described in section . . as we discuss in the main text, although for some states, the counterfactuals exhibit similar shapes to those regarding cumulative cases, for many other states, they are not statistically significant at least for the first days after the policy implementation. we know that lockdowns affect the covid- dynamics by imposing social distancing and mobility restrictions. to help understand the results described in this paper, we analyze the mobility data available at google mobility reports (https://www.google.com/covid /mobility/). google mobility data show how visits and length of stay at different places change compared to a baseline, before the outbreak of the pandemic. in particular, the baseline is the median value, for the corresponding day of the week, during the five weeks between january rd and february th . in order to understand how the population in each group (treated and control states) is behaving during the covid- crisis, we compute the median of mobility changes across our sample period, i.e. the days following the tenth day after the first confirmed case in each state. also, the data concern mobility changes for six categories, being five of them related to outdoor activities. namely, grocery & pharmacy, transit stations, parks, retail & recreation, and workplaces. the remaining one concerns indoor activities, namely, residential. hence, to capture an idea of outdoor mobility changes, we aggregate the aforementioned five categories into a single one defined as the median of the original five categories. in contrast, mobility changes in residential areas capture indoor mobility changes. the two boxplots in figures a. and a. present the median of mobility changes in all analyzed states both in residential and in outdoor areas, respectively. we report results for treated and control states separately. regarding mobility changes in residential areas, on average, residents from every state analyzed spent more time in these areas after the pandemic outbreak. however, those from treated states spent even more time indoor. nevertheless, there are outliers. for instance, residents from south dakota spent a lot more time in residential areas than before the pandemic, which helps understand the results found for this state in the placebo test. we found similar results for mobility changes in outdoor areas. clearly, residents from treated states remained in outside areas less often than residents from controls (always compared to the period before the pandemic). in new york, for example, there was a % decrease of outdoor mobility. once more, south dakota is an outlier for the control group, reinforcing the thesis that its population voluntarily decided to stay more at home. indeed, residents from south dakota spent almost % less time in outside areas, while those from the median state for the control group spent nearly % less. the economic costs of conflict: a case study of the basque country synthetic control methods for comparative case studies: estimating the effect of california's tobacco control program pandemic, shutdown and consumer spending: lessons from scandinavian policy responses to covid. working paper, university of 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benefits of closing businesses in a pandemic optimal mitigation policies in a pandemic: social distancing and working from home the effect of social distancing measures on intensive care occupancy: evidence on covid- in scandinavia. working paper counterfactual analysis with artificial controls: inference, high dimensions and nonstationarity ℓ -regularization of high-dimensional time-series models with nongaussian and heteroskedastic innovations short-term covid- forecast for latecomers. working paper villas-boas. are we #stayinghome to flatten the curve? working paper key: cord- -uu rbtem authors: andiman, warren a. title: where have all the “aids babies” gone? a historical memoir of the pediatric aids epidemic in new haven and its eventual eradication date: - - journal: yale j biol med doi: nan sha: doc_id: cord_uid: uu rbtem s.l. was one of our first hiv-positive babies. he was born at yale-new haven hospital (ynhh) in . his mother was a sex worker who also injected drugs. he died at ½ years following multiple episodes of opportunistic infection and metastatic lymphoma. in the years between and , hiv-positive mothers gave birth at ynhh. the mother-to-child transmission (mtct) rate was percent. women represented percent of all hiv cases in the us compared with percent in new haven. we had a six times greater proportion of children living with hiv. the mean number of hiv-exposed babies rose annually from ( - ) to ( - ). our first team of caregivers comprised a nurse practitioner, a social worker, and me. we were, in time, joined by a growing number of colleagues. enlightened and generous hospital administrators provided us with outpatient space and the promise of continued funding to support additional staff and in , an independent pediatric aids care program. we implemented the proven mtct prevention guidelines articulated in the pediatric aids clinical trials group (pactg) protocol and by , the mtct rate at ynhh fell to percent. since , the mtct rate at ynhh has been zero percent. combination antiretroviral therapy, cart, made its debut in the mid- s; five classes of drugs with multiple agents in each were licensed between and . we designed individual treatment plans for each child and gradually entered an era when our clinic was populated with healthier long-term survivors. our program flourished, based on a multidisciplinary approach which honored interprofessional collaboration. on the morning of january , , a jolting banner headline appeared on the front page of the journal-courier (new haven, conn., - : "candida lawler dies; autopsy due." the newspaper's publishers understood that their readers were already familiar with ms. lawler's story; articles revealing her identity had been published in the new haven register as early as february [ ] . her story received national attention when the cbs television news magazine, minutes, revealed grave concerns about ms. lawler, a -year-old woman living with hiv, and whether she and others who were similarly afflicted, should be quarantined. city officials believed that their isolation would stanch the spread of the deadly infection during high risk sexual liaisons with sex workers and sharing syringes during illicit drug use. shawn, ms. lawler's son, was one of our first three "aids babies" and the earliest to whom that label could be applied with certainty. he was born in september , and spent the first months of his life withdrawing from heroin and methadone-drugs that had traversed the placenta. ms. lawler had what are now known as significant risk factors for people living with hiv/aids, including drug use and engagement in sex work. rehabilitation efforts had failed. at the time of her premature death from aids-related pneumonia, the journal-courier mourned the "once vivacious and beautiful woman with long black coal hair…who now appeared aged and emaciated." she might well have been designated new haven's "patient zero," the first publicly-named and shamed aids patient in the elm city. however, a search of the medical records at yale-new haven hospital (ynhh) would have revealed names of at least a dozen additional patients living with hiv. lawler was one among many women living with hiv, but mother-to-child transmission was not yet widely recognized as a possible outcome of maternal infection. at age ½ months, shawn recovered uneventfully from a bout of bronchiolitis, but was re-admitted months later, lethargic, malnourished, and covered with a disfiguring purplish rash. he had hepatosplenomegaly and marked lymphadenopathy. his discharge diagnoses included disseminated meningococcemia and failureto-thrive. months later, he developed intractable oral thrush and candida diaper dermatitis. he had suffered hair loss, seborrhea, and eczema. he was thinner. these striking clinical signs, particularly his multiple infections and skin diseases, ultimately suggested an immunologic deficit. a comprehensive diagnostic work-up was undertaken. abnormal numbers of "atypical lymphocytes" were found in his blood and he failed to respond to skin test antigens. lymphocyte subset enumeration revealed far too few cd +t cells, an aberration shared with his mother. we had recently learned that these abnormalities were characteristic of a new disease, referred to by some as "grid," or "gay-related immunodeficiency disorder," "the gay plague." in the early s, the disease spread among men who had sex with men and intravenous drug users, including women. we wondered whether shawn, a toddler, was similarly affected. did ms. lawler pass hiv to her baby during pregnancy, at the time of birth, or perhaps, post-partum through breastfeeding. ms. lawler's blood was send to max essex's lab in boston. he had developed a test for human t-cell leukemia virus iii, htlviii, the name of the virus thought to be the cause of the world's newest immunodeficiency disease. ms. lawler carried antibodies to htlviii. (hiv was the name later assigned by an international congress.) shawn's blood carried the same antibodies. initially, we were unable to determine whether his antibodies were acquired from his mother in utero or were raised actively in response to his own infection. shawn followed an insidious downhill course, common in the early years of the epidemic. there were no antiretrovirals and few drugs to treat some of his multiple infections. at months of age, shawn was admitted to the hospital in respiratory distress. his chest x-ray revealed many large nodules and impressive mediastinal lymphadenopathy. cultures for the usual suspects were negative, but a lung biopsy showed evidence of lymphoid interstitial pneumonitis (lip), an entity only rarely reported in adults and almost never in children. lip was, for the first years of the epidemic, the most common aids-related illness in the pediatric population, an ominous predictor of advanced hiv disease. nevertheless, it responded temporarily to steroids and during his second year of life, shawn gained some weight, was less breathless and more playful. shawn presented with weakness of his left hand and face at age months. a ct scan of his head revealed a mass lesion deep in the midbrain. normal bone marrow was replaced by a b cell lymphoma. several courses of chemo-and radiotherapy stabilized his condition for almost a year, during which time he lived in a crib in an isolation room with other infants infected with hiv. the final event was an unrelenting metastatic infection with mycobacterium avium intracellulare (mac), resulting in grotesque enlargement of his regional lymph nodes, liver, and spleen. standard anti-infective agents and two experimental drugs donated by the cdc, ansamycin and clofazimine (neither of which is currently used), did nothing to change the course of the infection. shawn died at ½ years of age. hiv-infected babies began to appear regularly in the emergency room and various clinics. the obstetricians were caring for ever-increasing numbers of women testing positive for hiv. in new haven, the mean number of hiv-exposed babies rose annually from to ( - ) . in fact, percent of all babies born to mothers testing positive for hiv were also testing positive and in immediate need of complex and prolonged interdisciplinary care. we had moved into crisis mode. simultaneous with our need to devise an effective intervention, i had my first triennial leave, a mini-sabbatical during which i could devote myself exclusively to learning more about hiv and aids. previously, i had been involved in research studying the ways in which the epstein-barr virus displayed its pathology in both healthy and immunodeficient children. but now we were witness to the debut of a novel disease caused by a puzzling new virus, one that snared mothers and infants, in addition to men. new diseases weren't being seen that often-a rule that seems to have been broken with some frequency of late (viz. zika, west nile, mers, sars, covid- ). i reasoned that this was my chance to enter a challenging clinical arena on the ground floor, to make this growing plague the center of my academic focus moving forward. descriptions of pediatric aids came to us from the earliest epicenters as graphic retrospective reports. four of the "hot spots" were cities with large indigent populations, people who used drugs, men who had sex with men, and some of their female sex partners: new york city, newark, san francisco, and miami. the majority of babies were infected intrapartum with infectious blood and genital secretions, less so in utero. at the start of my explorations, i sought allies who could show me the ropes, introduce me to a few patients, and teach me some of the relevant clinical science. none of my usual teachers in the pediatrics department could help because they knew no more than i did, having read a few articles and listened to ominous stories on the news. so i made inquiries of colleagues in the department of internal medicine who had been caring for most of the patients. they all came up with the same name, leetha fraulino, aprn. i was surprised to learn that fraulino was a nurse practitioner who had come to ynhh from her previous position as a clinician with the greater new haven visiting nurses association. among her clients in the community were a handful of adult aids patients, some of whom had already spent some time in the hospital and some who were safely managed at home. she recognized the need for a place where the growing number of patients living with hiv could be followed in specialized settings, where they could receive both medical and much-needed psychosocial support. she imagined a place where preventive and supportive care, that included access to good nutrition and decent housing, would forestall the need for visits to the emergency department that frequently ended in moves to the icu. hospital administrators, alarmed by the increasing numbers of uninsured, critically ill patients and the uncompensated costs incurred in their care, agreed to give fraulino access to a few examining rooms in one of the ambulatory clinics for one afternoon a week. she was acquainted with many of her former clients and agreed to have me join her on her daily rounds. we reviewed x-rays, checked the results of laboratory tests, and shared insights we had gathered from the patients with the residents and nurses, including details of each one's social situation, and relationships with significant others and family. having anticipated a surge of hiv-positive babies, fraulino welcomed the chance to have a pediatrician as her ally. we were among the first troops on the front lines, joined in battle against a powerful new foe. i was hooked and my professional life was forever changed. the histories shared by most hiv-positive mothers and their female kinfolk indicated that their babies had been born into "at risk families." about half the mothers had used intravenous drugs which they often shared. some were sex workers and still others reported that they did not consume illicit drugs but had had sexual relationships with men who had. babies born addicted to drugs were immediately transferred to hospital units that were specially equipped to care for these irritable, tremulous, jittery newborns who sometimes spent weeks or months in isolettes at a distance from bright lights and disturbing sounds. they were swaddled and received round-theclock feedings on demand. among a series of impediments, we faced one insurmountable problem: we were not able to discharge hiv-exposed babies to the care of mothers still battling addiction; and experienced foster parents refused to take "aids babies" into their homes for fear of infection. there was only one alternative-the nurses, doctors, and social workers became their de facto guardians. the babies stayed in the hospital for months, sometimes for more than a year. in the early s, we cared for an average of hiv-exposed infants, born each year to hiv-positive mothers. we were obliged to track down a group of persons connected to each index mother, e.g. current and former sex partners, people who injected drugs, and older children. we invited them to meet with us to learn of their infection status. these meetings were long and excruciating. most of the contacts never imagined they might be carrying hiv, complicated by the fact that they might have already spread the virus to unknowing partners. they all needed to be directed to healthcare centers-destinations other than emergency rooms or the community, clinic, or hospital. physician specialists volunteered to help us in the clinics. they knew that aids was a growing epidemic, that they would soon be called upon. they wanted to be well-prepared, knowing they would become the teachers, transmitting their knowledge to the junior troops who were gathering close behind. well-concealed beneath the armor of denial and girded by their selfless efforts, there was sometimes a gnawing worry about the possibility of getting infected with hiv by accidental needlestick, a saliva or vomit-laden splash, perhaps by a urine, fecal, or blood-soaked bed, or maybe a bite or scratch by an agitated patient. (other than by sex or needle-sharing, the risk posed by other behaviors or body fluids was still unknown.) ynhh, the academic epicenter of medical care in southern connecticut, was committed to serving the entire population of new haven and the surrounding towns. its promise of excellent care for all who presented themselves was being challenged by the financial burdens incurred in caring for those who required costly emergency and prolonged intensive care. our team was called upon to educate an already receptive hospital administration. we were invited to present the facts of the epidemic, in all its alarming detail, to the hospital board of trustees. we reminded them that the uncontrolled demand for expensive care could be mitigated by creating a program devoted to longitudinal outpatient care for both adults and children, similar to those for patients with other chronic diseases. the caregivers would forge trusting relationships with their patients in a way that would ensure adherence to care and stimulate the creation of individualized care plans. we would introduce new treatments as soon as they became available. the social workers would focus their efforts on the financial, nutritional, and housing needs of the patients. timely arrangements could be made for in-home nursing care. we would strengthen the education of parents, spouses, friends, and neighbors. our first formidable ally was dr. john fenn, a surgeon and the hospital's chief of staff. he had heard of our work and already learned a bit about the clinical aspects of aids. he knew that the hospital was carrying a heavy burden and that babies and toddlers were beginning to fill isolettes in the nurseries and cribs on the wards. dr. fenn invited himself to make rounds with us a few times a week. he was deeply affected by what he saw and heard. after scrubbing, gowning, and masking, he would sometimes sit on the bed listening to patients' stories. he thanked fraulino and me and commended us for keeping abreast of every patient's status and carried these stories and descriptions of our daily routines to the hospital president, the chairmen of internal medicine, pediatrics, obstetrics and gynecology, and the vice president for nursing. in the wake of these meetings, fraulino and i "walk-in" clinics. those with substance abuse disorders were transferred to drug rehabilitation programs. women were given appointments with gynecologists who would provide access to birth control, cancer screenings, and treatment for sexually transmitted infections. we helped the homeless mothers, rejected by their families, to find housing and food stamps. by the mid- s, we had access to reliable antibody assays and both antigen and nucleic acid-based tests that allowed us to measure accurately the present status and arc of the epidemic in children and women of childbearing age. we compared the demographic features of hiv infection in new haven with the state of connecticut and the entire country. we learned that new haven was different! cumulative data through december , revealed that women represented percent of aids cases in the us compared with percent in new haven. similarly, children represented percent of all national cases compared with percent of our local cases. new haven had more than double the proportion of infected drug users compared with the rest of the country. in , the connecticut department of public health reported that one in every african american women giving birth in new haven was hiv-positive, a proportion twice that of all women giving birth in the state, regardless of ethnicity. national statistics revealed that connecticut ranked fourth per capita in the incidence of aids in women and first per capita in the nation in the incidence of aids in children. intravenous drug use by the mother or her partner was the risk behavior that precipitated infection in percent of the babies. in the us, the majority of patients were white ( % white, % black and hispanic) whereas in new haven, hiv infection was far more common in people of color ( % black, % hispanic, % white and other). we lived and worked in a small american city (population estimated , ) with a disproportionate onslaught of aids. we were crippled by a dearth of antiretrovirals and effective anti-infectives for many of the opportunistic infections. we needed more clinicians and financial aid to support our efforts. slowly, providers with a multiplicity of skills emerged from their quotidian workplaces and asked fraulino and myself if they could help. june holmes, msw, was one of the first to volunteer. she already knew some of the patients through her work in other parts of the hospital. like fraulino and me, she believed she would be most effective if she could serve our patients even before they were hospitalized and, again, at time of discharge. continuity of care was paramount, starting with the trust built during the first encounter, whether in interviewed on multiple occasions for articles in the new haven register, the new haven advocate, channel , the local tv station, and a few radio shows. i remember a few occasions when we chided reporters for having portrayed our patients in a light that may have stoked fear and derision among news consumers. it took some time to sensitize the media and other people of influence. in time, the hospital's board of trustees gave the go-ahead for the "official" creation of the "aids care program." soon the city of new haven and local charitable organizations joined us in common cause. fraulino, now the aids program coordinator and clinical supervisor and b. joyce simpson, rn, mph, once described in great detail the institutional response to the aids epidemic, using ynhh as the paradigm. they reminded us that public teaching institutions are responsible for making subspecialty expertise and stateof-the-art technology accessible to the public and local community needs and providing treatment with new antiretrovirals and anti-infectives. fraulino continued to see all the adults and children with aids-related diagnoses and introduced me to them as the medical director. she assessed their needs and assisted patients and their families to gain access to necessary support services. she participated in discharge planning in conjunction with the nursing and medical staff and developed a long-term plan for each patient. she organized the outpatient clinics and acted as the primary liaison between the inpatient and outpatient settings. in response to a growing patient population, the hospital mounted a second phase of planning. over the course of a year, we were introduced to additional subspecialists, with either adult or pediatric credentials. simpson became our pediatric research nurse and pediatric aids program coordinator. she collected, organized, and analyzed data that fulfilled the specific aims of our various grants. we also welcomed an educator with a graduate degree in public health who oversaw hiv testing and counseling services and two hiv counselors with backgrounds in nursing. the social workers guided families through the onerous process of applying for entitlements, including supplemental security income (ssi) and medicaid. finally, we developed cordial relationships with allies from pediatric and adult psychiatry, neurology, surgery, the chaplain's office, the child life program (evaluates developmental milestones and provides play therapy), nutritional services, respiratory therapy, and pharmacy. the team recognized the importance of establishing collaborative relationships with community-based agencies and organizations. we were living in the midst of a public health crisis and we saw ourselves as the catalysts for change. either individually or in pairs we educated leaders in the visiting nurses association, the methadone maintenance programs, the department of children and met with the same leaders to provide first-hand accounts in all their startling details. we made clear our need for funding and asked for official promises by the hospital and medical school to establish an aids care program, in perpetuity, dedicated to the ongoing outpatient and inpatient care of hiv-infected patients of all ages. we believed that health professionals on the front lines could be effective only with generous private and public support and the backing of two superlative academic institutions-ynhh and yale medical school. at the insistence of two successive chairs of pediatrics, doctors howard pearson and joseph warshaw, the hospital agreed to support half my salary. the pediatrics department would contribute much of the remainder to support my teaching efforts and a small percentage of my ongoing research projects. in a letter written in january , dr. fenn agreed to relieve me of some of my responsibilities in the adult aids effort, by funding two new half-time physician slots. both these physicians would serve the rapidly expanding adult population and i would be allowed to spend more time with the children who were hiv-positive and their families. the hospital also assigned us pediatric clinic space for one, and then two afternoons a week. full time rn and social service positions were added to the mix. dr. fenn penned an official note to dr. warshaw that fully acknowledged the work that fraulino and i had already done. he wrote the following: "the goal in the recent expansion of the program was to allow warren andiman and leetha fraulino some relief from their extraordinary burden and to make sure that the hospital was supplying resources commensurate with the magnitude of the epidemic facing us. i am comfortable that we are doing our part and that we have now provided dr. andiman with the help he most certainly needed and the opportunity to engage in other academic activities." ynhh serves the entire city of new haven, and with the university they are the city's largest employers. as such, the hospital and medical school are obliged to foster cordial relations with the city's leaders and provide them a voice in its stated missions. to keep these leaders apprised of the magnitude and severity of the "aids problem," g. harold welch, the president of the hospital, invited me to meet three city aldermen. after the dinner meeting, he wrote: "the three aldermen who attended are all members of the ynhh board of trustees." the meeting was designed to foster "helpful communication between the city's leaders, their constituents and the hospital. the hope was that the city would take appropriate action in the future." it did, in fact, "take a village" to support our program and keep its accomplishments in the public eye. the media started to take increasing interest in our work and in the changing state of the epidemic. fraulino and i were its attention on the rapid identification and treatment of aids-defining conditions, primarily opportunistic infections, but also certain malignancies, e.g. lymphoma and sarcoma, central nervous system afflictions, including aids encephalopathy, and chronic skin conditions. in the late s, treatments were limited, and cures were unattainable. the relentless pace of disability and disease continued. fifty percent of our hiv-infected children died before the age of years. most of our hiv-positive children had challenging home lives, including difficulties accessing food, transportation, and decent living conditions. their lives were chaotic, lonely, and stressful. some had already lost family members to aids and others faced the possibility of a parent's incarceration or hospitalization. following years of reluctance on the part of "professional" foster parents to bring babies living with hiv into their homes, we joined with the connecticut state department of social services and rolled-out intensive educational programs that featured infection control guidelines. the state increased payments to cover the costs of fostering a fragile, chronically ill child. these inducements encouraged some foster families to care for "aids babies." for the most part, these placements proved to have positive outcomes. there were impressive gains in growth and development and increased adherence to clinic visits and prescription refills. the number of hospital "boarder babies" slowly decreased and by , fell to zero. sometimes the child remained in foster care temporarily, until the mother was released from prison or committed to a drug treatment program. adequate housing was required for family reunification. remarkably, some foster families adopted the children they had nurtured so successfully. the minority of hiv-infected children who reached school age, were consigned to a space in the basement of a municipal building and were "taught" by someone with little or no requisite educational background or training. no classroom in new haven's public schools found space for a child living with hiv. the task of righting this discriminatory practice fell to the pediatric aids care program. our nurses, social workers, and i became community educators whose principal goal was to share the evidence that hiv is not spread by casual contact and that minor incidents of bleeding, spitting, urinating, and even biting, could be managed by the simple application of standard precautions: gloves, soap and water, and the prudent use of diluted household bleach, as needed. at some point, as the abysmally inadequate education of our patients was deemed untenable, i was asked to serve as families (dcf; formerly dcys, department of child and youth services), community aids support groups, like aids project new haven, churches sympathetic to our philosophy of care, connecticut hospice, and other long-term aids residency facilities. the collaborations resulted in improved care and a modest reduction in costs that would otherwise have been borne by the hospital. the pediatric aids epidemic in new haven grew at an alarming rate. along with the hiv-positive babies, who constituted percent of our patient population, we decided early on to continue to follow, temporarily, the percent of babies who had been exposed to the virus but were uninfected (some infants by ). we had to guarantee their safe release either to their biological mothers or to foster parents, often close relatives. we found placements for those "new" mothers who required drug treatment and safe housing. the early development of the now independent pediatric program mirrored in many ways the genesis of the adult program. therefore, we were not surprised when a willing group of talented, motivated, and energetic health professionals with diverse skills asked if they could help. we found assignments along the entire spectrum of their training-attendings, residents, post-docs, rns, aprns, social workers, nursing, and medical students. at the beginning, few of these assignments were designated as "official" and none was accompanied by bonuses or special treatment. these were professionals who incorporated their work with hiv-positive children into elective slots or a variety of required outpatient rotations. by , the hospital recognized the need to split the aids care program in two: an adult medicine arm and a pediatric arm. it was obvious that the number of patients needing urgent care was growing too rapidly to remain under the aegis of one medical director who had other clinical, research, and teaching obligations. also, my training as a general pediatrician with expertise in infectious diseases was no longer a good match for the enormous challenge posed by a population of seriously ill adults with life-threatening diseases and chronic conditions. the hospital set out to hire two experienced, academically-trained internists who had already served on the front lines of a city-wide aids epidemic similar to ours. the two saviors, gerald friedland and peter selwyn, by now leaders in the field, and both from montefiore hospital in the bronx, ny, joined the effort in to lead the adult program. in the absence of an effective antiretroviral agent, the pediatric aids care program initially focused much of . the regimen was comprised of antepartum zdv, given orally times daily, starting at to weeks post-conception and continuing through the remainder of the pregnancy. zdv was also administered to the mother intravenously during labor and delivery. the newborn received oral zdv syrup, beginning at hours postpartum and continuing every hours for the first weeks of life. periodic hiv cultures were done to distinguish between infants infected in utero and those infected intrapartum or postpartum. based on data derived from the mother-infant pairs who completed the study, zdv treatment was associated with a percent reduction in mtct ( % in the treatment group vs % in the placebo group). the drug regimen was well-tolerated. when the study results were published, the cdc recommended that the protocol be applied universally to all hiv-positive pregnant mothers. as per the cdc recommendations, we implemented the protocol and by , the mtct rate at ynhh dropped to percent, half the rate we witnessed previously. simpson, our pediatric research nurse made herself available, even at night, to attend the delivery of every hiv-positive mother. she guided the nurses and mothers through the steps of the pactg protocol. she met with each mother and learned about her social support system and living situation. she discovered whether there was money to buy formula, diapers, and clothing. the mother received her first -week appointment to the pediatric hiv clinic and a prescription for her child's zdv syrup. before hospital discharge, the nursing staff judged whether the mother could provide a safe home for her baby. the side effects associated with zdv were easily managed, but the inevitable appearance of resistance convinced us that additional antiretrovirals were needed to use in combination with zdv. combination treatment met its earlier success with regimens for tuberculosis and subsequently, for other complex infections and cancer chemotherapy, diseases in which drug resistance had been a significant obstacle to cure. we participated in large multicenter clinical trials assessing the utility of combining non-nucleoside reverse transcription inhibitors (nnrtis), e.g. nevirapine, with a growing number of newer nucleoside reverse transcriptase inhibitors (nrtis) e.g. lamivudine. in time, the protease inhibitors, entry/ fusion inhibitors, and integrase inhibitors were licensed sequentially in the decade between and . drug side-effects and resistance demanded that we follow the children closely and prepare to intervene with either temporary or permanent alterations in individual drug regimens. in good time, we witnessed varying declines in an expert witness in a complaint brought by the american civil liberties union against the city of new haven. based on the preponderance of the scientific evidence and the recognition that the children were being discriminated against on the basis of physical disability, a clear violation of the american disabilities act, the presiding judge found in favor of the right of hiv-positive schoolchildren to an education equal to their same age peers. as a result, our children gained admission to the city's classrooms with the promise that only the child's teacher, the school nurse, and the principal would be informed of the student's hiv status, an important concession that became operative in instances of accident or emergency. the most basic principle of public health, prevention, had not been fulfilled. we were treating disease but not preventing it. the fda approved the use of zidovudine (zdv, azt) to treat advanced hiv disease in adults. but we learned that zdv, the first in a new class of drugs, reverse transcription inhibitors, provided only short-term survival advantage and its benefits lasted only a few months. despite these disappointments, we convinced some of our pediatric pharmacists to create a syrupy concoction of zdv powder that could be fed by mouth to infants and toddlers. (once a drug is licensed, it can be used off-label if prescribers believe that the benefits outweigh the risks.) we knew of only two adverse reactions, mild anemia and liver dysfunction and monitored both by doing periodic blood tests that led to a change in dose or discontinuation of the drug, if necessary. as in adults, zdv treatment resulted in only temporary clinical improvement-weight gain, greater alertness and activity level, and fewer life-threatening infections. within a few years, the fda approved the use of zdv for children. we were buying time in the hope that more effective antiretroviral agents would arrive. clinical relief is not prevention. fifteen to percent of hiv-positive mothers were still transmitting hiv to their offspring and with some exceptions, the infected babies died before the age of years. nevertheless, we witnessed a veritable miracle in , when the results of the nih-funded study, pactg protocol was published. until that time, strategies for reducing the risk of vertical transmission of hiv were limited to the avoidance of pregnancy altogether or refraining from breastfeeding, which was the most common cause of postnatally-acquired hiv. the double-blind placebo-controlled study, pactg , investigating the effects of antiretroviral therapy during pregnancy, was initiated in the parties expressing vehement objections argued that administering hiv tests by way of blood draw to newborns, absent informed consent and expressly against the will of the parents involved, constitutes an illegal search, forbidden under the fourth amendment to the us constitution. the cha filed a motion for a temporary restraining order enjoining the execution and enforcement of the law a mere "scant hours" before the law was scheduled to go into effect. because the judge presiding over the us district court concluded that the plaintiff had not proved the likelihood of success in demonstrating that the statute at issue was unconstitutional, the motion for a temporary restraining order was denied and the law went into effect. despite the law, by there was only limited evidence that providing antiretroviral therapy to the newborn would lessen the severity of infection, even if there was no prior treatment of the mother during the latter part of pregnancy, labor, and delivery. we now know that early postnatal treatment does lower the viral load in the infant and limits damage to the immature immune system. we also know that the discovery and treatment of hiv infection in a previously untested mother may be lifesaving and nearly always prevents vertical infection in all subsequent births, if the mother continues her treatment. connecticut public act no. - was the powerful tool we were waiting for. we went into the community and educated physicians who cared for pregnant women. we urged them to become familiar with the new statute and to call us with questions. our nurses constructed detailed protocols for the labor and delivery floors. the mothers were given postpartum appointments to the high risk obstetrics clinic and their infants made visits to the pediatric hiv clinic at weeks of age, while still receiving oral zdv. we had foreknowledge of the impressive preliminary results of the pactg prevention study and had been following its guidelines, even before the study was published. this head start and our intensive educational efforts in the hospital and community resulted in a steady decline in the number of newborns testing hiv-positive. the last infant that tested hiv-positive was born at ynhh in . for each of the past years, we have screened and treated about twenty hiv-positive pregnant women, a significant decrease from earlier decades. none of the babies born to hiv-positive mothers between and late were infected. nevertheless, we still care for a few hiv-positive children who have come to us from other parts of the world, mainly africa, and for a handful of adolescent men who have had sex with older hiv-positive men. viral loads and rises in cd + t-cell numbers to more normal levels. many of the children felt better and returned to their regular activities, including school attendance. as with adults, combination therapy with an ever-increasing number of agents, altered forever the natural history of pediatric hiv infection, changing it from a rapidly fatal to a chronic, manageable disease, including for some who had survived beyond early childhood. despite these gains, our pre-eminent wish remained unshaken, i.e. to eradicate mtct of hiv, a goal that would prevent the life-long morbidities and suffering that accompany pediatric hiv infection and its attendant limitations and stigma. the pactg protocol, when practiced consistently, proved to be a lifesaver. for all mothers at risk who sought prenatal care and were not already being treated with antiretrovirals, hiv testing was offered. if the test results were positive, simple drug regimens were prescribed along with intensive counseling and admonitions to adhere closely to the instructions for drug compliance. hiv care and obstetric care were linked. when close to term, the mothers were given explicit instructions to appear early in labor, so that zdv could be administered intravenously before their baby's birth. but routine hiv screening was not yet part of obstetric care and it soon became obvious that we were missing some women at risk: those who failed to receive prenatal care and those who did receive care but whose hiv infection status was unknown or not recorded. we posed an audacious question: shouldn't hiv testing be a mandatory part of obstetric care? in the early years, hiv testing was permitted only after a counseling session and signed consent. times change. connecticut public act no. - became law on october , after much contentious opposition mounted by the connecticut civil liberties union foundation, the connecticut hospital association (cha), and by editorials and harsh opinion pieces in local newspapers. the first part of the law read as follows: [ ] ." ( . %) had been mildly symptomatic or asymptomatic; c). ( %) were seroreverters, i.e. they permanently lost all passively-acquired maternal antibody and were uninfected; d). % were deceased and . % were lost to follow-up. once we had optimal practices in place for preventing mtct of hiv and managing the care of children who survived without the burden of lifelong infection, we formally joined the pactg. the pactg (now impaact) is a consortium of academic pediatric institutions charged with testing the efficacy of new antiretrovirals and anti-infectives. we also tested live virus vaccines for their safety in hiv-positive children whose immune function had been restored by antiretrovirals. lastly, we participated in a detailed collaborative natural history study of hiv-infected and hiv-uninfected peers who were exposed to hiv perinatally, i.e. affected but not infected. ultimately, between the years and , we enrolled scores of children in one or more clinical trials each. the results of these studies meant healthier and more productive lives for thousands of infected and affected hiv-affected children worldwide. among hiv-positive children born prior to , about half, our longer-term survivors, were healthy enough to attend school free of the bane of aids-related conditions. many children were lucky to have found loving foster families who later adopted the children they had raised. the number of "active" patients in in our care fell by percent in the decade ending in . the survivors met with our caregivers every to months. eighty percent ranged in age from to years; percent were older than , and percent were younger than years. fifteen children died in the years between and , half in the hospital and half at home or in hospice. there were only three deaths between and . among our long-term survivors (lts), adverse medical and social issues are common. their outcomes have ranged from excellent to poor. over percent have maintained undetectable viral loads and cd + t-cell counts in the normal range. the number of emergency visits and hospitalizations has fallen precipitously. however, non-adherence to medical regimens, unprotected sexual intercourse, stigmatization, unchecked family discord, depression, and school drop-outs have stymied the realization of the fully successful social and physical outcomes we had hoped for. many families failed to disclose the hiv diagnosis to their children for fear of precipitating untoward psychological repercussions, including long-term stigma. some hiv-positive young after a half dozen years of familiarizing myself with the protean manifestations of pediatric aids, i began participating in research studies that would answer pressing clinical questions. i re-examined the statistics extracted from older studies conducted without benefit of appropriate study design and methodologies. intending to correct these deficiencies, i set myself the task of embarking upon a prospective, longitudinal cohort study to determine the true risk of mtct of hiv, the relationship between the degree of immunodeficiency and the incidence of aids-defining illnesses and survival, and the connection between specific gestational variables and transmission risk. between and , i was awarded an uninterrupted series of grants and contracts, the first few of which were designed to answer definitively the questions i had enunciated. the earliest of my grants coincided with the inauguration of two private foundations created to support basic and clinical research on hiv and aids: amfar (the american foundation for aids research) and egpaf (the elisabeth glaser pediatric aids foundation). we joined an international alliance of american and european academic centers and our collective data ultimately became the basis for what we now know about the epidemiology, pathogenesis, and natural history of pediatric aids. among the most important of our local and international collaborative findings were the following: i). among babies born to hiv-positive mothers and followed since birth at ynhh between the years and , the overall risk of transmission of hiv was percent (range - %); ii). the risk of mtct was percent for mothers who received no antiretrovirals during labor and delivery versus percent for mothers who received antenatal and intrapartum antiretrovirals and whose newborns received zdv for the first weeks of life (as per pactg protocol ); iii). among ynhh mothers who received antiretroviral therapy during pregnancy, the risk of mtct was percent for those whose cd +t-cell counts were < cells/ul versus percent for those mothers with median cd + t-cell counts > / ul; iv). a meta-analysis of more than a dozen prospective cohort studies (including ours) by the international perinatal hiv group demonstrated that elective c-section before onset of labor and before rupture of membranes, resulted in a decline in the risk of vertical transmission from percent to percent. when c-section was combined with antiretroviral therapy during the third trimester, the risk of mtct of hiv fell further, to percent; v). among hiv-exposed children enrolled in our prospective study (including those enrolled in collaborative studies during which they had received varying lengths and combinations of antiretrovirals), we recorded the range of clinical outcomes in : a). ( . % had been severely or moderately symptomatic; b). women and men became parents unintentionally, but all their offspring are uninfected (all the pregnant young women complied with their prenatal clinic appointments and took their medications). a minority of our lts have completed high school, college, or job-training and a few have been successfully employed. a handful have been incarcerated on drug charges or acts of violence. one patient, lost to follow-up, died by gunshot. those of us working in resource-rich countries encountered the "coming of age" of the first and largest cohort of hiv-positive children-those born between the early s and the late s. we confronted their need for a major health care transition. data collected by the cdc in , revealed that approximately , american youth, ages - years, were living with hiv/aids. this was a percent increase from , attributed to high-risk adolescent sexual behavior and increasing survival of children infected perinatally. developmentally appropriate youth ought to receive care in adult healthcare practices sometime in their early s. but there are numerous everyday tasks that represent major hurdles for many teens, in particular adherence to their medical regimens. ultimately, with diligent guidance, most of them progress to a point where they can be safely transitioned. during the years - , under the guidance of sostena romano aprn, mba, our longest-serving nurse practitioner, and anne murphy, msw, we transitioned patients, ages to years of age, to adult practices: to yale's adult nathan smith clinic, nine to other hospital-based clinics in connecticut, and eight to private practices close to the patients' homes. we have continued this practice as our patients enter late adolescence and young adulthood. the eradication of mtct of hiv in new haven was made possible by the confluence of six nourishing streams: ). the creation of effective antiretrovirals, anti-infectives, and sensitive diagnostic tests; ). the flood of grants and contracts from federal, state, local, and private funding agencies; ). wise and generous support from yale-new haven hospital and the department of pediatrics; ). the passage in of connecticut public act no. - ; ). the creation of an effective multidisciplinary approach to care which honors respectful interprofessional collaboration; ). the spontaneous and enthusiastic union in common cause of doctors, nurses, social workers, students, administrators, and volunteers to serve patients in need, their families and friends, in new haven county and beyond. rethinking complicity in the surveillance of sex workers: policing and prostitution in america's model city special session reduction of maternal-infant transmission of hiv- with zidovudine treatment european collaborative study: children born to women with hiv- infection: natural history, and rate of transmission a prospective cohort study of children born to hiv-infected mothers. trend in the risk of vertical transmission, mortality, and aids-indicator diseases public act no. - duration of ruptured membranes and vertical transmission of hiv- : a meta-analysis from prospective cohort studies update on successes and challenges regarding mother-to-child transmission of hiv- transition from pediatric to adult healthcare services for young adults with chronic illnesses: special case of human immunodeficiency virus infection this term was widely used in medical circles and the media in the s to refer to hiv-exposed infants who faced lengthy hospitalizations to ease them through withdrawal from opioids and/or cocaine as they awaited foster home assignments. the term has disappeared now that the rates of vertical transmission of hiv have fallen to negligible numbers. names of patients have been changed to protect their identity. all babies born to hiv-infected mothers are "hiv-positive" until to months of age because they all acquire hiv antibodies transplacentally. but only a fraction are "hiv-infected." eighty percent are "exposed" to hiv and are temporarily hiv-positive, but remain "uninfected." unfortunately, in late , an hiv-positive baby was born at ynhh after a gap of years. the teenage mother received prenatal care at a clinic unaffiliated with ynhh. she was non-compliant with the antiretroviral regimen that was prescribed for her. she was surprised to learn that her newborn baby was infected. the baby received antiretrovirals soon after birth, the mother's regimen was re-started, and the baby's biological father appeared for testing and treatment. all three have been adherent to their various regimens and, as of last report, all are doing well. since the start of we have followed nine hiv-exposed babies, but no mother-to-child transmissions of hiv have occurred. key: cord- -d df authors: quast, t.; andel, r.; gregory, s.; storch, e. a. title: economic losses associated with covid- deaths in the united states date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: d df in addition to the overwhelming health effects of covid- , the disease has inflicted unprecedented economic damage. vast resources have been directed at covid- testing and health care while economic activity has been substantially curtailed due to disruptions resulting from individual choices and government policies. this study estimates the economic loss associated with covid- deaths in the u.s. from february , through july , . we use estimates of years of life lost that are based on the age and gender of decedents. using a value of life year estimate of $ , , we calculate economic losses of roughly $ billion. the losses are concentrated in new york and new jersey, which account for . % of the total losses. our analysis of per capita losses by state indicates that the highest values are located in the northeastern region of the country, while the values in the western states are relatively low. while economic losses associate with covid- deaths is just one aspect of the pandemic, our estimates can provide context to the value of prevention and mitigation efforts. while the health effects of covid- are devastating, the economic effects of the pandemic are also profound. estimates suggest that if % of the population were infected, the direct medical costs in the united states (u.s.) would be roughly $ billion (bartsch et al, ) . these costs include testing, ambulatory care, hospitalizations, and extended treatment of long-term effects of the disease. the economic costs also include the reduction and, in some cases, complete stoppage of economic activity due to government policies and individual behavior. these costs have been estimated to reduce real gross domestic product (gdp) growth by % per month (makridis and hartley, ) . another important component of the economic costs of covid- involves losses due to deaths from the disease. while the approaches are imperfect, economists have long attempted to estimate costs of deaths due to actual or potential policies and events. a common approach is employ value of a statistical life (vsl) estimates. generally, the number of deaths is multiplied by the vsl to estimate the economic cost. this approach is used by u.s. government agencies (robinson, ) and by researchers in areas such as transportation (rizzi and ortuzar, ; dua, ) , health interventions (laxminarayan et al, ; sproul et al, ; scharff, ) , and environmental studies (franchini, ; lee et al, ) . while these analyses are informative, a significant drawback is that they do not explicitly account for the age profile of the decedents. for instance, under this approach the same value is assigned to a newborn as is assigned to a very sick individual near death. this paper estimates the economic losses associated with the roughly , covid- deaths in the u.s. from february , to july , . our approach employs years of lost life (yll) estimates, which are based on the age and gender of the decedents, reported in quast, et al ( ) . we estimate the economic losses associated with covid- deaths to be roughly $ billion. our general approach is to multiply the ylls by an estimated value of each life year. this strategy has been used in studies of areas including health behaviors (nonnemaker et al, ) , pollution (desaigues et al, ; grandjean and bellanger, ; kim et al, ) , and health outcomes (temkin et al, ; pezzullo, et al, ) . our yll estimates are based on an analysis by quast et al ( ) of data contained from the "provisional covid- death counts by sex, age, and state" published by the national center for health statistics in the u.s. centers for disease control and prevention (cdc). these data separately report deaths for new york and new york city and do not contain data for wyoming. quast et al ( ) . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . ; https://doi.org/ . merged the death counts with life expectancy estimates by age and gender obtained from actuarial life tables published by the u.s. social security administration. for each age-gender group, the unadjusted yll estimates were obtained by multiplying the number of individuals in that group by the difference in life expectancy and the age at death. the population-wide number of ylls was found by summing across the age-gender groups. as noted by hanlon et al ( ) , those who died of covid- often had pre-existing morbidities which may have otherwise prevented them from reaching their life expectancy. the authors created a model of covid- deaths in the united kingdom that used data from italy and found that, adjusting for preexisting morbidities, the average estimated ylls for men fell from to and for women from to . our primary specification follows quast et al ( ) and reduces the life expectancy of decedents by % to reflect the typically lower pre-covid- health status of those who died. a value of life year (voly) estimate must be identified to calculate the economic cost associated with ylls. we employ a value reported by desaigues, et al ( ) that was based on a stated preferences approach. they asked residents of european union countries their willingness to pay for policies that reduced pollution and, thus, increased life expectancy. their estimate of , euros has been employed in previous economic loss calculations (temkin et al, ; grandjean and bellanger, ; kim et al, ) . the value converted to u.s. dollars is $ , . we also calculated economic losses using lower and upper benchmarks ($ , and $ , ) employed by the institute of clinical and economic review when conducting cost-effectiveness analyses (institute for clinical and economic review, ). however, these benchmark values are based on quality-adjusted life years and are not directly comparable to voly estimates. we discounted future dollar amounts by % per year. to estimate per-capita values, we use population data from the "annual state resident population estimates" published by the u.s. census bureau as of july , and were obtained by gender. we obtained the population of new york city and the percentage of population by gender as of july , from "quickfacts: new york city, new york" published by the u.s. census bureau. table details the economic losses using our primary voly estimate of $ , and the two benchmark icer values. the values are based on reducing the life expectancy estimates by %. appendix table reports the values for our primary voly estimate and life expectancy reductions of % and %. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . ; https://doi.org/ . the total estimated losses associated with covid- deaths in the u.s. during our analysis period were roughly $ billion. the losses were highly concentrated among the top states. new york city alone accounted for roughly . % of the total losses while new york city, new jersey, and new york state (excluding new york city) combined incurred over one-third of the total losses. the top ten jurisdictions accounted for roughly % of the total losses. the human toll of covid- is devastating and takes precedence when considering the pandemic's effects. however, estimates of the economic loss can provide context in terms of the cost of prevention and mitigation efforts. deaths are just one aspect of the toll of covid- , but are arguably the most important. we estimate the total economic loss due associated with covid- deaths in the u.s. to be roughly $ billion which, if extrapolated to an annual basis, corresponds to roughly . % of the u.s. gdp in . we observe large absolute and per capita losses in the northeast region of the country while the western region of the country generally has lower per-capita losses. as noted above, another potential approach to estimate economic losses due to deaths is to base the calculation on the vsl rather than on the projected number of years of life lost. vsls are typically estimated via either stated or revealed preference for how much compensation an individual would demand to incur greater risk. using a vsl of $ . million (viscusi, ; viscusi and masterman, ) , the corresponding economic loss associated with the , deaths is roughly $ . trillion, a value roughly eighteen times greater than our estimate. economic loss estimates based on volys and vsls are not directly comparable, but the wide range of the two values suggest that adjusting for the relatively older age profile of covid- decedents has a substantial effect on economic loss estimates. our analysis has several limitations. most notably, we only estimate losses associated with deaths. costs due to other aspects such as hospitalizations, long-term health effects, and reductions in economic activity need to be included in an estimate of the overall cost of covid- . our reduction in projected life expectancy by % is an approximate value. however, we believe it is a conservative approach that reflects the current understanding of covid- mortality risk. we used a single voly estimate for the . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . ; https://doi.org/ . / . . . doi: medrxiv preprint entire country which does not reflect potential variation in valuations across states. further, if an estimate was available, it would be preferred to use an estimate based on surveys of u.s. rather than e.u. residents. finally, our analysis period only represents the early stages of the covid- outbreak in the u.s. as the virus ebbs and flows throughout the country and additional lives are lost, both the total economic loss but also the ranking of jurisdictions will change. the authors declare that they have no conflict of interest. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted october , . ; https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted october , . ; https://doi.org/ . the potential health care costs and resource use associated with covid- in the united states economic valuation of air pollution mortality: a -country contingent valuation survey of value of a life year (voly) national mandatory motorcycle helmet laws may save $ . billion annually: an inpatient and value of statistical life analysis the health and economic burden of air pollution calculation of the disease burden associated with environmental chemical exposures: application of toxicological information in health economic estimation covid- -exploring the implications of long-term condition type and extent of multimorbidity on years of life lost: a modelling study final value assessment framework: updates for - health and economic consequences of applying the united states' pm . automobile emission standards to other nations: a case study of france and italy valuing vaccines using value of statistical life measures evaluating the pm damage cost due to urban air pollution and vehicle emissions in seoul, korea key: cord- -x fcib authors: mcdonald, robbie a.; birtles, richard j.; mccracken, christina; day, michael j. title: histological and serological evidence of disease among invasive, non-native stoats mustela erminea date: - - journal: vet j doi: . /j.tvjl. . . sha: doc_id: cord_uid: x fcib invasive, non-native species are a major threat to global biodiversity. stoats were introduced from britain to new zealand in the s and have since caused grave conservation problems. a histopathological and serological survey of disease and infection in stoats from new zealand was undertaken to identify agents that might be used or modified to control this population. of stoats examined, % exhibited inflammation of the lung, mostly occurring as local or diffuse interstitial pneumonia, % showed signs of inflammatory liver disease and % were positive for antibodies reactive with feline calicivirus. in britain only % of stoats exhibited symptoms of pulmonary inflammatory disease, suggesting higher rates of infection or compromise of the pulmonary immune system among invasive stoats, possibly related to genetic founder effects or environmental variation. these findings could be exploited in biological control programmes. invasive non-native species are among the greatest threats to global biodiversity (atkinson, ) . non-native species often increase their populations rapidly in a novel ranges where they may be free of the factors, such as disease and predators, that limit populations in their native range. alternatively, they may be exposed to new pathogens that have the potential to prevent or reduce the rate of establishment (hilker et al., ) . this may particularly be the case when small founder populations with reduced genetic diversity render newly established populations particularly vulnerable to novel infections (hawley et al., ) . the ecological impacts of invasive species are most pronounced on islands which are often home to a diversity of endemic species that are naïve to predation risk (simberloff, ) . introduced mammals are the single gravest threat to biodiversity in new zealand (king, ) . predators, such as stoats mustela erminea, are a particularly serious problem since many of new zealand's endemic birds have evolved in the absence of predators (king, ) and there has been considerable public expenditure on large-scale culling of stoats with the aim of reducing stoat predation (mcdonald and murphy, ) . given that conventional methods of stoat control are limited to trapping and poisoning which are expensive, there are moves towards identifying more cost-effective methods of long term and widespread control of stoat predation. these include conventional biological control using lethal or sub-lethal pathogens and immunocontraception, potentially using a disseminating vector that would be genetically modified from a widespread, host-specific infectious agent (norbury, ; mcdonald and larivière, ) . this clearly requires knowledge and comparison of the diseases stoats encounter in their native and non-native range. mcdonald and larivière ( ) provided a comprehensive review of the diseases and pathogens of stoats and other mustelids, generally in their native range, but with particular reference to the control of invasive stoats in new zealand. studies of the general biology of stoats in new zealand have provided basic data on the prevalence of certain parasites, such as the nematode skrjabingylus nasicola, the adults of which infects the sinuses of various mustelids, and of ectoparasites (king and moody, ) . a histopathological survey of naturally occurring disease among stoats living in britain concluded that stoat populations in their native range were remarkably healthy, since % of stoats exhibited no significant pathological lesions at the microscopic level . among british samples, nematode parasitism was identified in the intestines of % of stoats and in the lungs of %. pulmonary granulomatous inflammation or microgranulomas were identified in % and blood-filled, peliosis-like cavities in the livers of two individuals. the objective of this study was to provide information about the incidence of disease in free-living, invasive stoats in new zealand, compare the prevalence of disease in the non-native and native ranges and to relate this to possible founder effects. this information will also inform decisions about the future direction of research into the biological control of invasive stoats. samples were collected opportunistically from conservation rangers and researchers in addition to hunters and other members of the public who trapped or shot the animals as part of their normal pest control procedures. samples were taken from a range of locations and habitats in south island, new zealand, between january and june . blood and tissue samples were extracted as soon as possible after death. a range of tissues was collected and fixed in % neutral-buffered formalin solution, including brain, heart, lung, kidney, liver, mesenteric lymph node, thymus, spleen, stomach, duodenum, pancreas and colon. extraction and fixation of samples was undertaken by field personnel and whole animals were not available for inspection of gross pathology or of age-structure. a haematoxylin and eosin (he) stained section was prepared from each tissue and was examined by light microscopy for pathological change. where he stains clearly indicated the presence of an infectious agent, a panel of further stains (gram, periodic acid-schiff and ziehl-neelsen), was conducted in order to provide further diagnostic information. all examinations were conducted by a board-certified veterinary pathologist (mjd). sera were screened with immunofluorescence assays (ifas) using viruses grown in various cell lines using standard laboratory protocols. lymphocytic choriomeningitis virus (lcmv) ifa slides were purchased from charles river diagnostics ( -well slides, sl- ) and the assay was performed as per manufacturers' protocol except that bound antibodies were detected using a goat anti-ferret immunoglobulin g fluorescein isothiocyanate isomer i conjugate (igg-fitc, bethyl laboratories inc.) used at a / dilution. all other viral ifa antigens were produced in-house. briefly, each virus was grown to a standardised titre in a suitable cell line (see below) in a -well microtitre plate, and was then fixed by the addition of % alcohol to each well. prior to use, wells were washed and rehydrated in phosphate buffered saline (pbs). each serum sample was diluted to in and in in pbs and tested in duplicate: ll of serum dilutions were added to each well and incubated for - h (depending on the assay) at °c in a moist atmosphere. identical dilutions of a positive control serum standard (though not from a stoat) and a negative control serum standard were also included on each plate tested. after repeat washing with pbs, ll of the anti-ferret igg-fitc conjugate (see above), diluted in , was added to each well and plates were reincubated at °c for h in a moist atmosphere. wells were then rinsed repeatedly in pbs, then loaded with ll of glycerol for examination under suitable epifluorescence at · magnification. results (positive fluorescence) were assigned to each sample by reference to the positive and negative control standards. viruses for use in the ifas described above were grown in the following cell lines: canine distemper virus (morbillivirus) and cowpox (orthopoxvirus) -vero cells, canine parvovirus- and canine coronavirus -a cells, feline calicivirus -feline embryo (fea) cells, canine adenoviruses i and ii and canine herpesvirus -madin derby canine kidney (mdck) cells. tissue samples from stoats and sera from of these were analysed. samples were collected from nine locations ( fig. ). the sex ratio was not significantly different from parity (overall males:females = . : , g c = . , p > . ). on the whole, preservation of tissue structure was remarkably good. samples from the intestinal tract were most affected by autolytic change, but in most cases the 'ghost outline' of the underlying tissue permitted some analysis of tissue structure. summary comments on the appearance of the major organ systems are presented below. most lungs had evidence of either focal or diffuse congestion/haemorrhage, interpreted as agonal change. most (n = , %) also had evidence of diffuse or focal interstitial pneumonia involving infiltration of neutrophils and macrophages (pyogranulomatous) (fig. ) . in five of these cases, there was additional involvement of the bronchi with neutrophilic exocytosis into the bronchiolar lumena (bronchopneumonia). some lungs had evidence of balt aggregates, but this was not a consistent feature. parasitic larvae were not identified within the pulmonary tissue. there were occasional focal and well-defined microgranulomas. one of these centred upon fragments of aspirated matter and two had large, crescentic, translucent structures at the centre reminiscent of the adiaspores of the fungus chrysosporium (fig. ) . myocardium, endocardium and epicardium were almost invariably normal. in two stoats there was evidence of a mild and focal myocarditis -generally involving a mixed mononuclear cell infiltration. the majority of stomachs were histologically normal. in six stoats, there were small focal granulomatous infiltrates at the base of the glandular mucosa, sometimes extending into muscularis mucosa. in several of these cases there were parasitic larvae in the centre of these aggregates, suggesting that these lesions were attributable to larval migration (fig. ) . sections of the duodenum, ileum, caecum and colon were largely normal. pancreatic tissue was generally normal (both exocrine and endocrine) and it was noted that stoats have very prominent islets relative to some species. in two cases, there was evidence of interstitial pancreatitis. the majority of samples of liver were histologically normal. seven had evidence of diffuse hepatocyte vacuolation. other livers had focal (centrilobular) vacuolation of hepatocytes which is a non-specific change. occasional portal areas had a mild, mononuclear cell infiltration but this was rarely above what would be considered background in other species. several livers had small parenchymal (mid-zonal) foci of hepatocyte degeneration and mixed inflammation (focal hepatitis). two had evidence of vascular telangiectasis, and in one of these cases there was a relatively large area of hepatocyte loss, blood pooling and surrounding granulomatous inflammation (fig. ) . no significant abnormality was found in any kidney but one sample showed evidence of a single small focus of interstitial lymphoid aggregation. longitudinal sections of spleen were all remarkably similar in appearance and the spleen was invariably markedly active. the white pulp (lymphoid) areas were extremely prominent, often with very large secondary follicles dominating. red pulp was not often severely congested, but was always very cellular. the cellular content of red pulp included lymphocytes, plasma cells, and megakaryocytes were often prominent indicating extramedullary haematopoiesis. also of note in red pulp was the presence of a population of very large, blastic round cells with an open-faced nucleus and prominent nucleolus. these cells may have been lymphoblastic. in one or two spleens this population dominated, and the cells were so large and pleomorphic in appearance that in other species their presence may have suggested neoplasia. mesenteric lymph nodes were all very similar in appearance, consistent with marked immunological activity of the gut. there were very prominent secondary follicles with germinal centres and mantle zones, frequent paracortical hyperplasia and dilated medullary sinuses with sinus histiocytosis. the brain was histologically normal in the majority of stoats, with no evidence of lesions consistent with viral infection (e.g. distemper virus). in one stoat there was a focal, granulomatous meningitis that affected the meninges ventral to hindbrain, this animal was seropositive for lymphocytic choriomeningitis virus (arenavirus), though a link between these observations is not certain. in another stoat there was mild focal gliosis within the parenchyma. testicular structure and ovarian tissue, including the fallopian tube, were generally histologically normal. in one stoat, there were granulomatous plaques covering a number of abdominal viscera, with granulomatous disease of the lung and meninges. this animal appeared to have a systemic granulomatous inflammatory disease. sera from eight individuals ( %), seven of which were from one site (grebe valley), were positive in the feline calicivirus antibody assay. three individuals, two of which were from a single site (reefton), were seropositive for morbillivirus, a family that includes canine distemper virus. two individuals were positive for parvovirus antibody, including one that was one of the three stoats that were positive for morbillivirus. single, separate individuals were found to be positive for antibodies reactive with ortho-poxviruses, lymphocytic choriomeningitis virus (arenavirus), and canine herpesvirus. all sera were negative for canine adenovirus and coronavirus. there was no evidence of a relationship among samples between seroprevalence of virus antibodies and histopathological evidence of disease. there was no significant relationship between the incidence of inflammation in one organ system and another (p > . in all cases). as in the survey of stoats in their native range , many of these individuals had histologically normal tissues and were likely to have been in good health at the time of death. opportunistic sampling, such as that used here, may not reflect the prevalence of disease among the sickest individuals in the population, since these may be less mobile and less likely to be caught or may die particularly quickly. this is a consistent but unavoidable characteristic of such screening studies of wildlife disease. the consistently marked activity of the spleen and the prominent lymphoid areas of the spleen suggest that stoats have a functional systemic immune system and an active systemic humoral (antibody) response. in common with the british samples, no lesions of the brain were observed that would have been consistent with infection by distemper virus, though this can not be taken as evidence of the absence of this disease and three individuals in this study were seropositive for morbillivirus, which is comparable to a recent finding of two seropositive animals from a sample of stoats sampled in canterbury, new zealand (t. zheng, personal communication). two cases of bloodfilled cavities in the liver were observed in stoats, similar to the peliosis-like lesions observed in two british stoats. at the time, we suggested that the british samples may have been secondarily exposed to rodenticides and this remains a possibility for the new zealand specimens (mcdonald et al., ; murphy et al., ) . positive results for feline calicivirus were the most significant findings of the serological survey. these feline viruses are generally very host-specific and so these findings are strongly indicative of infection with a mustelid calicivirus. it is not possible at this stage completely to rule out cross-reaction with rabbit caliciviruses that include rhd, which have previously been recorded in stoats in new zealand (henning, ) . however rhd is caused by a separate genus of caliciviruses lagovirus whereas cat caliciviruses are vesivirus. cross-reaction across genera and such a broad host range is unlikely. caliciviruses can cause a range of pathologies in their hosts ranging from upper respiratory tract infections in cats to gastroenteritis in humans. four of the stoats found to be seropositive to calicivirus exhibited histopathological signs of inflammatory lung disease. however, the prevalence of these signs of disease was particularly high across all stoats examined and so it was not possible to demonstrate an association between disease and infection by calicivirus. an earlier review of mustelid pathogens, with reference to stoats in new zealand, (mcdonald and larivière, ) did not identify calicivirus in stoats, but noted the reported but unsubstantiated association of calicivirus (together with escherichia coli and coronavirus) with ''sticky-kit disease'' in ranch mink mustela (jorgensen et al., ) . mink caliciviruses (mcv) have been isolated from mink on ranches with a history of haemorrhagic pneumonia (evermann et al., ) . however, mink enteric caliciviruses have been shown to be genetically distinct from non-enteric calicivirus (guo et al., ) . this is clearly, therefore, a diverse group and while it is novel that calicivirus has been detected in stoats, it is not surprising. this screening study is a first step towards evaluating the incidence and effects of calicivirus in wild stoats. however, the finding holds promise in terms of identifying potentially widespread viral infections that may have a role as biological control agents or as vectors thereof. our histopathological findings differed to a surprising extent from the british survey. in particular, we detected a significantly higher prevalence ( %) of pneumonia of varying degrees of severity, while pulmonary inflammatory disease was detected in only / ( %) british stoats ðv c ¼ : ; p < : Þ. while this is a screening study, it is tempting to speculate on the implications of these findings. the widespread incidence of pneumonia suggests that stoats are subject to a higher rate of infection of some agent, which may be more prevalent in new zealand or notably less prevalent in great britain. alternatively, the pulmonary immune system of stoats in new zealand may be compromised in some way. the cause of the high incidence of pneumonia could not be detected by histopathological techniques and our serological investigation could not reveal the association of exposure to any of the tested virus groups with these signs of disease. in the development of a biological control agent or candidate vector for an immunocontraceptive, the identification of the organism causing the inflammation observed here is an obvious first step. thereafter, a search for an organism, or strain of the same infecting organism, that invades hosts through the lungs would be especially useful. potential causes of pneumonia in mustelids are numerous (fox, ) and there is evidence of viral-bacterial synergism in the symptoms of severe pneumonia (jakeman et al., ) . mink and ferrets are also susceptible to avian influenza (buchman et al., ; englund and af segerstad, ) . during a review of diseases of stoats and related mustelids, mcdonald and larivière ( ) identified a range of diseases in which horizontal transmission may occur through the respiratory tract, perhaps the best known of which are tuberculosis and paratuberculosis caused by mycobacterium spp. (ragg et al., ; beard et al., beard et al., , . curiously, while pulmonary inflammation was common and pulmonary parasitism rare among new zealand stoats, inflammation was rare and parasitism common in the lungs of british stoats (mcdonald et al., ) , which is suggestive of interactions between the immune responses to different pathogens. similarly, rates of arthropod-borne infections such as those caused by bartonella spp. among new zealand stoats are markedly lower than occur in britain (mcdonald et al., , , suggesting differences among pathogens in the rate at which diseases and/or their arthropod vectors were transported between native and non-native ranges. examination of tissues from other invasive predators collected contemporaneously in new zealand has provided an interesting comparison to samples from the stoats. two of three weasels, a ferret and one of three feral cats examined exhibited interstitial pneumonia and granulomatous inflammation similar to that observed in the stoats (mcdonald et al., ) . clearly, a similar range of lesions were present in these other species. this confirms the importance of investigating host specificity in the development of any putative biocontrol agent. in summary, this survey has provided evidence of a range of tissue lesions in otherwise healthy stoats in their non-native range in new zealand. the high frequency of pneumonia and the discovery of calicivirus among invasive stoats are perhaps the most significant findings of the study, which hold significance both as indicators of the potential relationship between genetic founder effects and susceptibility to disease and the application of these traits to the control of invasive species and their impact on biodiversity. introductions of 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virus: possible role in sudden infant death syndrome escherichia coli and virus isolated from 'sticky kits immigrant killers: introduced predators and the conservation of birds in new zealand the biology of the stoat (mustela erminea) in the national parks of new zealand diseases and pathogens of mustela spp., with special reference to the biological control of introduced stoat mustela erminea populations in new zealand a comparison of the management of stoats and weasels in great britain and new zealand anticoagulant rodenticides in stoats (mustela erminea) and weasels (m. nivalis) in england diseases and pathogens of stoats in great britain. unpublished report to the director general of conservation (contract ). department of conservation histological evidence of disease in wild stoats mustela erminea in england diseases and pathogens of stoats and other wildlife in new zealand. department of conservation brodifacoum residues in target and non-target animals following largescale poison operations in new zealand podocarp-hardwood forests the potential for biological control of stoats (mustela erminea) the prevalence of bovine tuberculosis (mycobacterium bovis) infections in feral populations of cats (felis catus), ferrets (mustela furo) and stoats (mustela erminea) in otago and southland extinction-proneness of island species -causes and management implications the new zealand department of conservation (doc) funded this work as part of the stoat research programme, research investigation . r. mcdonald was supported during part of this work by a royal society postdoctoral fellowship hosted by the department of biological sciences, university of waikato and is supported by the quercus partnership between environment and heritage service and queen's university belfast. we are grateful to m. bennett, j. duckworth, s. jones, c. king, e. murphy, g. norbury, d. prout, d. purdey, w. ruscoe, g. taylor, i. yockney and staff of landcare research and doc for assistance with sample collection, transportation, preparation and analysis and for advice and comments on the manuscript. key: cord- - ef qy authors: lombardi, jm; bottiglieri, t; desai, n; riew, kd; boddapati, v; weller, m; bourgois, c; mcchrystal, s; lehman, ra title: addressing a national crisis: the spine hospital and department's response to the covid- pandemic in new york city date: - - journal: spine j doi: . /j.spinee. . . sha: doc_id: cord_uid: ef qy in a very brief period, the covid- pandemic has swept across the planet leaving governments, societies and healthcare systems unprepared and under-resourced. new york city now represents the global viral epicenter with roughly one third of all mortalities in the united states. to date, our hospital has treated thousands of covid- positive patients and sits at the forefront of the united states response to this pandemic. the goal of this paper is to share the lessons learned by our spine division during a crisis when hospital resources and personnel are stretched thin. such experiences include management of elective and emergent cases, outpatient clinics, physician redeployment and general health and wellness. as peak infections spread across the united states, we hope this article will serve as a resource for other spine departments on how to manage patient care and healthcare worker deployment during the covid- crisis. although from an early age i'd learned from charles darwin and others that species adapt naturally to their environment, in the moment, that adaptation is often a painful process. the onset of covid- and the changes forced upon us by science, common sense, and our survival instinct have been a strong reminder of the challenges true adaptation involves. this spring's events have felt familiar to me -i'd already lived a similar experience. in the first weeks after taking command of joint special operations command (jsoc), it became apparent we were losing the battle to al qaeda in iraq (aqi). jsoc, america's elite counter-terrorist task force, was built to operate in small teams conducting elegant, but infrequent, precise strikes. we were the most efficient and effective counter terrorism force in existence -but we were not adaptable. we'd never really had to be. al qaeda in iraq (aqi), however, changed the rules by morphing faster than our slow, but precise, operations could counter. a target, or fleeting opportunity, that was located in the morning was typically gone by evening. against an enemy that operated differently than anything we had seen before, we had to change. unsure of what the right answer was, we started from the reality that the one course of action for which we had reliable data, the status quo, was failing. so, we adopted a policy of "question how we do everything". nothing was held sacredwe needed to find out what worked to defeat aqi and we needed to do it quickly. it was disconcertingly disruptive for a force inclined to developing and then refining to near perfection our tactics, but it worked. we iterated adaptations until jsoc became instinctively flexible and wickedly fast. the reality for most organizations is that they do not adapt until they are forced to do so. what is often touted as a leader's foresight or vision was really driven by the reality of a burning platformchange or grow irrelevant; adapt or die. for america's healthcare teams, the fight against covid- is not just the search for a vaccine or management of ventilators. it is adapting every aspect of managing the care of patients. leveraging virtual interaction, mining growing bodies of data, and realizing that not all care will wait until we return to status quo anteit has to continue on now, but safely. and it must be delivered by healthcare professionals who are performing the extraordinarily complex tasks they always have, but now in the vastly more difficult covid- environment. all this is doable, because it has to be. it's also possible because the patient-centric mindset that drives the people who've chosen to care for others will drive it. it isn't easy and won't get much easier -but it's working and will only get better. on december st , , local health officials in the chinese province of hubei reported cases of a mysterious pneumonia to the world health organization (who) . while viral pneumonias are commonplace, this cluster was particularly unusual in that a high percentage of patients was responding poorly to typical supportive measures and becoming critically ill. it was soon recognized that this illness was being caused by a never-before-seen coronavirus subsequently named the severe acute respiratory syndrome coronavirus (sars-cov- ) with its infectious manifestation termed the coronavirus disease (covid- ) - . the outbreak was reportedly centered on a wet market in the city of wuhan, china, but quickly spread the speed and intensity with which the virus spread has left governments and healthcare systems unprepared, under-resourced and without enough personnel to adequately respond. particularly hard hit has been new york city, which is now one of the global viral epicenters. as of april th , there were a staggering , mortalities in new york city alone, representing over % of all covid- -related deaths in the united states . according to the university of washington's institute for health metrics and evaluation (ihme), the peak hospitalization rate in new york will occur during the second week of april, preceding the majority of the united states . our institution has been on the forefront of the covid- pandemic, as we treated "patient zero" in new york city, who presented to our emergency department (ed) on february th . to date, we have treated over , covid- positive inpatients in the epicenter of the viral pandemic with strained resources. our experiences may serve as a model for other institutions to prepare as their regions approach peak infection. therefore, the purpose of this paper was to describe our orthopaedic departments' approach towards ) management of elective cases and outpatient visits, ) management of "emergent" surgical cases, ) redeployment of orthopaedic personnel, and lastly ) maintaining protection and well-being within the department. published data by healthcare providers in asia and europe demonstrated that the most substantial threat to covid- patient morbidity and mortality was the lack of adequate critical care resources including intensive care unit (icu) beds and respiratory support [ ] [ ] . early reports from lombardy, italy, exposed the strain of widespread community transmission on hospital icu capacity consultation or a telemedicine consultation. telemedicine visits were found to be noninferior with % of virtual visits rated as "good" or "very good" by surgeons there can be ambiguity when attempting to determine which surgical procedures are elective, urgent or emergent. additionally, conflict may arise among healthcare providers when attempting to prioritize cases in the setting of severely limited personnel, resources and ventilators. therefore, our institution sought to create a two-step process to determine both the urgency of cases and the order in which they should proceed. first, a directive was given to create clear guidelines for determining surgical urgency from both an institutional as well as a departmental/divisional standpoint. those cases that met institutional and departmental criteria were then directed to an independent hospital panel that would determine their priority. at the time all elective cases were cancelled, our institution published criteria for case escalation, which would serve as a basis for categorizing the urgency of cases across all sites. (figure ) emergent cases were classified as those that are life or limb-threatening and would require access to the operating room within minutes. these cases would allow for "bumping" of any service into any available operating room when applicable. urgent cases were defined as those requiring an operating room within eight hours and would allow for "bumping" within their surgical service (i.e. orthopaedics bumps orthopaedics). add-on cases were defined as those that should be performed within - hours, lending priority to long bone fractures. lastly, the "to consider" classification was given to those patients whose cases were not time sensitive, but whose discharge from the hospital was pending surgical intervention. the institution published a sample list of cases across all specialties and where they fall into the criteria for escalation. to date, there are no published articles detailing how to best allocate resources and prioritize urgent/emergent cases within a spine division during times of crisis. on april anonymous to the public and employees of our institution. we have received many calls from colleagues across the country whose hospitals have established an intradepartmental committee to determine which cases are urgent or semi-emergent. yet without anonymity, it is impossible to remove personal interests from the decisionmaking, which may be at odds with key members of the team. when making decisions on the urgency and priority of cases, this committee takes into account guidelines from the cdc, who, new york state department of health and new york city department of health, as well as appropriate subspecialty academy guidelines. in an environment with limited hospital resources and personnel, this committee serves to remove the ethical and legal burden from surgeons while also serving the best interests of not only the patient but also the community as a whole. it is important to note that there are limitations to this system, which include review of cases by surgeons and/or lay people that is outside of their direct area of expertise. . it is not currently the standard of care for surgeons to be wearing n masks while operating, thus potentially exposing them to substantial risk in the period following intubation. with this understanding, the use of n masks and full-face shields has quickly become implemented into our operative ppe protocol. in an effort to protect both our patients as well as our staff, our institution has mandated that all patients be tested for covid- with a nasal swab viral pcr when admitted to the hospital and prior to proceeding to the operating room. recognizing these potentially devastating risks to the operative team, our department developed a protocol in conjunction with the department of anesthesia that is designed to minimize exposure to aerosolized viral particles. we identified three distinct phases during the surgical episode where attention should be paid in order to limit transmission: ) or preparation, ) intubation and ) extubation. during this phase, one should remove all non-essential equipment from the operating room such as iv poles, iv pumps, rapid infusor systems, suture cart etc. medication and equipment expected to be needed during the case should be removed from the anesthesia cart and the drug-dispensing unit and placed on a clean, easily wipeable surface. one should close all drawers, cover the anesthesia cart and drug-dispensing unit with a plastic drape, and try to avoid accessing it during the case. one should have emergency medication and equipment nearby in a closed bag, so it is easily accessible if needed but does not get contaminated during the procedure. the anesthesia machine has to be protected with a hepa filter. with very few exceptions, most spine surgeries require endotracheal intubation. operating rooms are a positive pressure environment. therefore it is recommended that if a negative pressure room is available, the patient should be intubated there and then transported back to the operating room. if such a room is not available, the intubation will take place in the operating room. after preparation of the or as detailed above, all non-essential personnel, including the surgical team, should leave the room. all anesthesia providers must wear ppe including n- masks, impermeable gowns, face shields or goggles, double gloves, shoes and head covers. additionally, a transparent drape should be placed over the patient's head, neck and shoulder area to contain the area of potential respiratory expectorants during induction. this drape can be removed after completion of the intubation process. the patient should be pre-oxygenated for several minutes. a rapid-sequence induction to achieve optimal intubating conditions in the shortest possible time is the preferred method of induction. this avoids mask ventilation with highly aerosolizing potential. a video-laryngoscope is preferred for intubations as it allows the anesthesia provider to keep greater distance from the patient's oral cavity. the endotracheal tube cuff should be inflated immediately, the endotracheal tube (ett) should be connected to the anesthesia circuit and etco confirmed. it is vital at this time to adequately secure the endotracheal tube. although an endotracheal intubation is an aerosolizing procedure, an unsecured airway over the whole length of the surgery may have greater potential to create aerosolized viral particles than the intubation itself. for auscultation of breath sounds a disposable stethoscope should be used. patients presenting for spine surgery, in particular surgery involving the cervical spine, frequently require other methods of securing the airway. in order to protect the patient from further injuries to a potentially unstable cervical spine or in patients with an anatomically difficult airway, a fiber-optic or an awake fiber-optic intubation is often the only safe method of endotracheal intubation. these procedures carry a very high risk of contaminating the environment by respiratory expectorants and should be avoided if possible. if necessary, they should be performed in a negative pressure environment. putting the patient in a prone position usually requires disconnection of the ett from the circuit in order to minimize risk of ett displacement. in these patients the anesthesia practitioner should carefully weigh the risk of ett displacement versus aerosolizing infectious material when disconnecting the ett. the surgical team is advised to re-enter the operating room only after the air has circulated through one cycle, which will vary depending on the specific number of air changes per hour set by that institution. the surgical team and support staff are advised to wear n masks throughout the procedure with appropriate eye protection. if the situation requires an awake fiber-optic intubation in the positive pressure environment of the operating room, the surgical team should consider entering the operating room after the air has circulated through several cycles in order to reduce the viral load in the air. standard ppe with an n respirator and eye protection is of course paramount for all practitioners entering the operating room. if a negative pressure room is available, the patient should be transferred after completion of surgery for removal of the endotracheal tube. it is recommended to cover the patient's face and upper torso with a clear plastic drape and extubate under that cover in order to avoid dispersing infectious material. standard ppe has to be worn and all non-essential personnel should leave the room, whether extubating in a negative pressure environment or in the operating room. patients should be extubated to nasal cannula, face tent or nonrebreather facemask. high flow nasal cannula and bi-pap should be avoided due to the high potential for viral aerosolization from these oxygen-supplying modalities. if possible, nebulized medications should likewise be avoided because of the highly aerosolizing nature of this application method. it became clear from an early point that the prospect of orthopaedic surgeon redeployment to other areas of need within the hospital was a distinct possibility. this was due in part to anecdotal reports of redeployment in viral epicenters as well as through correspondence with colleagues in europe and asia. moreover, on march rd , the governor of new york mandated that all hospitals within the state increase their icu capacity by % . this increase in capacity had to be met with an increase in skilled workforce including nursing staff as well as physicians. by march th , exactly one month following the presentation of patient zero to our institution, the first orthopaedic team was redeployed to the ed. in order to spread the burden evenly across our department, a committee was convened by remote meeting and charged with planning redeployment strategically. it was decided to deploy teams of two providers to the ed, composed of one attending and one resident. each volunteer was asked to submit his or her age and medical comorbidities, which were kept anonymous to the rest of the department. risk factors for severe covid- infections were identified and included age > , htn, dm, cv disease, obesity and immunosuppression . other considerations taken into account included child-care needs and ability to quarantine from members of the household. lastly, those who had a known or suspected prior covid- exposure and had recovered were placed at the top of the list under the assumption that they had obtained short-term immunity, although at this time it is unclear if or when immunity to sars-cov- is conferred. ( figure ) an antibody test, when available, will also help in the risk stratification as a significant number of healthcare workers have likely been exposed but are asymptomatic or have a mild illness with immunity. housing outside of primary residences was made available for volunteer faculty and house staff to help eliminate concerns about spreading the virus to one's family. faculty and house staff were then ranked for deployment depending on their risk stratification. it is vital to note that although redeployment was an important initiative to our department during this time of crisis, our primary concern was to maintain an adequate workforce to meet all orthopaedic surgical demands at our institution. when structuring the redeployment schedule, the risk to providers must be considered. it became clear that the number of exposures and duration of exposure should be limited to avoid overburdening clinicians in covid positive areas. while - hour shifts may be preferred among some surgeons, we advocated for shorter, - hour shifts to spread the risk out over a larger number of clinicians. the logistics of this type of deployment limit the number of times in each shift that ppe needs to be donned and doffed and also reduces fatigue. ultimately deployment shifts were split between multiple departments which further limited repeated exposure to our team. (figure ) . these teams would rotate to ensure that needs in the ed were met at all hours of the day, every day of the week. initially, orthopaedic surgeons and urologic surgeons shared ed coverage. eventually, otolaryngology and ophthalmology joined the redeployment efforts. the staffing for these deployments should be based upon the skill set of the respective surgical services. several of the spine surgeons (and especially the neurosurgeons) have intensive care unit (icu) experience, and may be better off deployed to assist with the ventilated patients. due to aggressive measures taken by the hospital to divert low acuity patients, the total number of daily ed visits was not dramatically increased. however, the acuity of patients who necessitated prolonged icu stays rose significantly. this led to increased critical care needs within the ed and the icu. while the precise duties of redeployment vary depending on the assigned location, the overall role of the orthopaedic surgeon was to provide support to the critical care team. typical duties included obtaining arterial blood gasses for ventilated patients, placing orogastric and nasogastric tubes, assessing for adequate sedation, adjusting ventilator settings, monitoring vitals, ordering blood pressure support and sedative medications, communicating between medical and consulting teams, and even aiding in patient transport between the units. particularly challenging was the preservation of ppe due to its critically short supply. due to the virus' capacity to be aerosolized, n masks are recommended wherever aerosolizing procedures are commonly performed, primarily the ed and the icu . these procedures include intubation, extubation, bronchoscopy, cardiopulmonary resuscitation (cpr), non-invasive positive pressure ventilation (nippv), high flow nasal cannula, and nebulization. ideally these procedures would be performed in a negative pressure room, but with the high volume of patients necessitating these procedures in the ed it was not deemed possible. given the significant shortage of ppe, each provider was given one n mask at the beginning of his/her shift and expected to wear that mask throughout the shift or until it was visibly soiled. in order to prevent the n from becoming contaminated by droplets, it was covered with a typical surgical mask followed by a face shield. when the n mask had to be removed, such as for eating or drinking outside of the unit, the surgical mask would be replaced, allowing the respirator to be in times of crisis, the similarities between physicians and soldiers become more evident. both professions play an irreplaceable role in our society, seeking to serve for the greater good of the public. the following lessons have been adapted from soldiers' accounts in the battlefield and applied to our experiences during the covid- pandemic . . embrace the buddy system: the environment that healthcare providers face during the covid- pandemic will in many ways be unfamiliar. this includes exposure to a novel pathogen that can endanger the health of physicians working on the front line. having a "battle buddy" will serve as a physical and psychological crutch to keep providers out of harm's way. during our department's redeployment, battle buddies were charged with making sure their partner always had proper ppe, maintained safe procedural practices, and assisted in collective medical decision-making. . prepare for the unexpected: rarely in our nation's history have healthcare systems been stretched so thin in such a short amount of time. it is vital for departments to remain flexible and prepared for worst-case scenarios. this includes lack of adequate ppe, team members unable to contribute due to illness, surges of new patients and absence of typical support staff. taking the time to reflect on "what can go wrong" will enable institutions and departments to be better prepared. . this is a team effort: in every organization there are members who contribute to varying degrees. it is vital for the leaders in each department to recognize what each of their members' strengths and weaknesses are and to utilize them appropriately. by involving the entire department in decision making and redeployment, leaders can achieve camaraderie and a common sense of purpose. in our department, we recognized who was at higher risk for complications from the covid- pandemic and deprioritized them for redeployment. those providers instead increased their telemedicine visits as their primary contribution. our department recognized the dangers that fatigue can have on physicians who were deployed to covid positive areas. any lapse in stringent airborne and droplet precautions can have catastrophic repercussions. for this reason we implemented battle buddies, abbreviated and rotating shifts, and frequent breaks into our redeployment plan. time away from the hospital also helped to alleviate the emotional or psychological stressors that physicians were exposed to. it has been shown that in times of national and international disasters, there can be an increased mental health burden on the population city, such as the september th attacks, task forces were assembled for crisis management. similarly, population-based strategies are currently being employed today. on a more individual level, our department started a "buddy" system, as described previously, at the beginning of the isolation period to ensure active engagement with peers. we also established connections with our departments of psychology and psychiatry for individuals to engage with mental health support as needed. engagement of faculty with meetings arranged through teleconference platforms was implemented early on to maintain education and peer interaction. throughout the covid- pandemic, in an effort to maintain resident learning and training, our department has continued all educational conferences by use of teleconference software. this includes departmental meetings such as the monthly morbidity and mortality conference. the och spine hospital began with monday and wednesday morning educational video teleconferences, and maintained our usual wednesday "huddle" (rotating between research meetings, morbidity and mortality conference, attending meetings and high-risk case conferences). additionally, we have established a wednesday morning national educational series among several institutions, and a thursday evening meeting that is attended by over surgeons worldwide. these allow us to maintain our national and international platform, and garner information from other institutions that are at different stages of the pandemic. it is important to note that social distancing for healthcare workers also includes distancing within the home. we have recommended that clinicians who are redeployed pack a second set of clothes to change into after doffing the uniform they used to treat the covid- positive patients. they are recommended to then remove those clothes prior to entering their home, sometimes through an accessory entrance if possible, and place everything in a laundry bag to be immediately cleaned. they should then proceed immediately to the shower to decontaminate. it is recommended to use a different bathroom than other occupants in the household. if this is not possible, one should immediately clean the bathroom with disinfectant after use. surgical masks are donned in the home and social distancing during meals and other interactions should apply. if allowable, one should sleep in a separate part of the house or apartment. some clinicians prefer housing quarters away from the home although this has not been explicitly recommended by health authorities. each institution should attempt to provide resources for available housing. it is well documented that routine physical activity can have a profound impact on both overall health as well as mental wellbeing [ ] [ ] . this is particularly true when socially isolating and remaining less active at home. multiple phone and computer applications are available to help stimulate physical activity routines . it is advisable to decrease regular exercise routines to % of the prior level of fitness to help stimulate the immune system and avoid paradoxical immunosuppression . regular nutrition and hydration are also necessary for optimal performance. part of the rationale for recommending a shorter duration of shifts is to avoid dehydration or the repeated donning/doffing that would be required over the course of a -hour shift to maintain adequate hydration and nutrition. physicians and surgeons often work continuously without a break in crisis scenarios and busy wards, leading to depletion of glycogen stores and dehydration. if one must work longer shifts, administrators should be sure to have a safe space for doffing and storing ppe for hydration and snack breaks. additionally, supplying food can help to increase the likelihood that clinicians will eat during a long shift. while we are hopefully nearing the apex of the curve in new york city, we know from other countries that this pandemic and its devastating effects will continue to roll across the united states in the coming months. we wanted to write this paper to provide some basic guidance, tips and pearls that we have learned as the "tip of the spear" in our country's fight against the pandemic. we recognize that the above recommendations are the product of clinical expertise at a single institution with currently limited knowledge of the covid- pathogen. as such, treatment protocols, resource utilization and deployment strategies are likely to change as more is understood about this disease process and the unique challenges it places on every affected institution. looking ahead, we know life will forever be different. similar to the world wars and / , these events transform our very fabric of existence. as general mcchrystal stated in the foreword, in combating any enemy, an age-old axiom is to "improvise, adapt and overcome." indeed, the resiliency of the american spirit and those of our healthcare heroes will eventually overcome this invisible enemy. it will now be up to our country's leadership to prepare for the next catastrophe, pandemic, war or other challenge. we will be better prepared next time, and hope this experience serves to inform hospital systems across the united states and the rest of the world. as george santayana stated in , and winston churchill paraphrased in his speech in , "those who fail to learn from history are condemned to repeat it." early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia a new coronavirus associated with human respiratory disease in china clinical characteristics of coronavirus disease in china a pneumonia outbreak associated with a new coronavirus of probable bat origin who declares covid- a pandemic novel coronavirus and orthopaedic surgery: early experiences from singapore papa 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know aerosol and surface stability of sars-cov- as compared with sars-cov- new york state mandates an increase in hospital bed capacity clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study. the lancet ten tips for a crisis: lessons from a soldier psychological interventions in times of crisis mental health status of doctors and nurses during covid- epidemic in china. available at ssrn a meta-analysis of physical activity in the prevention of coronary heart disease the influence of physical activity on mental well-being. public health nutrition the best fitness apps exhaustive submaximal endurance and resistance exercises induce temporary immunosuppression via physical and oxidative stress key: cord- -q tjbwui authors: millard, william b. title: surgeproofing the hot zone: preparing for a second wave of covid- date: - - journal: ann emerg med doi: . /j.annemergmed. . . sha: doc_id: cord_uid: q tjbwui nan a s the front line of the american health care system's defense against the novel coronavirus sars-cov- q and the associated coronavirus disease (covid- ) , emergency departments (eds) have borne the brunt of the initial onslaught since the global pandemic reached the united states last winter. the very novelty of covid- , in multiple senses-immunologic novelty for a population lacking herd immunity, clinical novelty in its diversity of presentations, and sociocultural novelty in that it has appeared amid nationwide tumult and institutional distrust-makes it a perfect storm. it has caught much of the united states unprepared. yet despite the many uncertainties about covid- , emergency physicians have gained critical practical knowledge. when the second wave strikes, it is imperative to apply what they have learned from recent experience and from epidemiologic history. the concept of a second wave is a matter for debate because much of the country is by no means past the first one. (the "wave" metaphor itself can be misleading, said epidemiologist marc lipsitch, dphil, of harvard's t. h. chan school of public health in a new yorker interview, because of its implication that case and mortality figures ebb and flow naturally and symmetrically, rather than as consequences of policies, interventions, and behavioral decisions. the image of a forest fire, prone to sudden instability when sparks meet tinder, struck dr. lipsitch as more appropriate. ) at this writing, the national epicenter of covid- , the new york city metropolitan area, has succeeded in flattening its new-case and mortality curves since their spring peaks through lockdowns, social distancing, masking, and first-responder resilience. concern that businesses and activities may be reopening too quickly drives predictions that the fall and winter will see deadly resurgences. "i do think a second wave is coming; it's just a matter of when, and how big is that wave going to be," said nancy conroy, md, associate chief of service in the ed at new york university langone hospital-brooklyn and clinical associate professor at new york university grossman school of medicine. a focus on the epicenter alone can be misleading. "most of the country did not have the experience that new york, chicago, detroit, new orleans, [and] even seattle had," observed donald m. yealy, md, chair of the department of emergency medicine at the university of pittsburgh school of medicine. "much of the country looks more like western pennsylvania, where there was an increase in activity, but it was accommodated within the health care system." in some locations, however, that slower-breaking first wave, combined with uneven test availability, may have contributed to a false sense of security: areas where the populace has adopted preventive practices less rigorously have seen new cases begin to soar. the johns hopkins coronavirus research center's daily case report indicates the sharpest rises in arizona, texas, and florida at this writing, with several other sunbelt states' data also looking alarming. by publication, other locations may be the hottest of this disease's diverse hot zones. dr. yealy provides historical perspective. "the timing of the peak, the intensity and height of the peak, and then how long that stayed really vary," he noted. "that's been true of viral pandemics since the beginning of time. they do not enter every geographic location at the same time with the same intensity, and they respond differently for reasons that we don't really understand." diagnostic whack-a-mole p recautions, dr. yealy has found, do not require predictions. "i think you should be probabilistically aware but respond to the realities. i think fear is a great motivator for both patients and health care providers." the practical questions, he suggested, include "what's the infection going to look like? how many people are going to be sick enough to require hospital care, and maybe to have interventions to prevent bad outcomes? and will we be able to do all those things?" thomas q spiegel, md, ms, associate professor of emergency medicine at the university of chicago, described a common adaptation that aids both transmission control and triage: early in the pandemic, his ed separated its space, including waiting rooms, into zones. "we essentially have eds within any ed," dr. spiegel said. "we have [one for] influenza-like illness and a covidlike illness-most places, i think, refer to it as the hot zone-and then the cold zone, which is the non-[influenza-like] illnesses." covid- 's long asymptomatic or presymptomatic carrier state expands uncertainties and complicates triage. centers for disease control and prevention data from covid- antibody tests in patients undergoing routine screening for other purposes (eg, cholesterol testing) at sites around the country indicate that estimates based on seroprevalence and catchment-area populations far outstrip the known cases. "for every case reported," centers for disease control and prevention director robert redfield, md, told reporters, "there were actually other infections." new york university langone epidemiologist stephanie sterling, md, credits isolation measures with damping the initial surge in the northeast but warns against complacency. "the risk is much lower now, but it's going to creep up," she said. "as people start getting more comfortable being more social, especially in the fall when we have to start maybe coming indoors more, that's the biggest concern: that we've pushed the virus down to very low rates of transmission [but] we haven't gotten rid of it, and if we have a number of days where we are not respecting how bad this virus is, it's just going to come back and bite us in the butt." although the classic covid- clinical presentation involves fever and respiratory distress (sometimes upper, sometimes lower, and not always a conventional upper-to-lower progression), the virus has also produced atypical effects that are only beginning to be understood. new york university langone-brooklyn is a level i trauma center, dr. sterling noted, and "we saw a number of people coming in with falls-no other symptoms whatsoever-and then because we had the capacity at some point to test everyone coming into the hospital, we started seeing a lot of people [for whom] that was their presenting symptom for covid." these patients did not have fevers and upper respiratory infections that were missed on the initial history, she noted; "it really was 'i was fine and then just fell.'" c ertain precautions for either a resurgent or a continued wave are accepted universally. personal protective equipment (ppe) was in notoriously short supply in the early stage of the outbreak. ensuring adequate ppe and adapting facilities in ways that conserve this resource by reducing repeated donning and doffing will be essential to safeguard staff before waves of new cases again become overwhelming. dr. choe q returned from los angeles to the site of her residency at new york-presbyterian hospital when she heard about new york's spring outbreak. she currently practices bicoastally, maintaining voluntary affiliations with columbia and cornell, as well as ucla (both the quaternary hospital and a community clinic in downtown los angeles that serves an underserved population); she vividly recollects how practice atmospheres evolved since early reports arrived from wuhan and italy. "essentially, all the other patient populations were disappearing from the patient list," she said; patients would arrive "with oxygen saturations that were not sustainably low and were ultimately intubated and placed on ventilators, and i would hear these stories over and over again that to ventilated patients on breathing machines were in our ed, just coming in [in] droves, and the hospital continued to try to find room for them.at a faster pace than there were ventilators, as well as providers and space." work conditions could be primitive as well as stressful. at the height of the pandemic, she recalled, "the [centers for disease control and prevention] had made an announcement that bandannas or handkerchiefs could be [used] as a substitute for high-grade ppe, and there were pictures of people wearing trash bags as gowns." as a part-time mba student at ucla anderson school of management, dr. choe helped organize ppe drives and raise funds to help alleviate these shortages in clinics, hospitals, and communities around la. in new york, she has seen disturbing inequalities in supply distribution: "i think it should not have required a social media presence of health care workers, and for health care workers to get sick and themselves die from coronavirus, in order for hospitals to have received the standard equipment that they deserve." testing remains essential to covid- management, although serologic tests may not be all that informative until more is known about the duration of immunity. timing affects the accuracy of both serologic tests and polymerase chain reaction-based diagnostic tests. a cochrane library review of antibody-test studies chain reaction tests found falsenegative rates of % on the day of symptom onset, % on day , and % on day . waiting for test results as long as a week, dr. conroy noted, can make them clinically irrelevant-"a lot can change in to days"-and she believes rapid-turnaround tests will be indispensable when influenza and other seasonal viral illnesses begin to complicate the differential diagnosis. still, the false-negative rates remain a cause for concern. other pointers worth emulating are relatively low tech. positioning patients prone has improved outcomes, dr. spiegel noted, and the literature supports this simple intervention. , dr. conroy's ed had "teams that would go around the hospital on shifts to turn patients over to help recruit additional lung tissue, and we found that that was actually very beneficial." early concerns about ventilator shortages may have been limited to the hardest-hit cities. dr. yealy noted that "at the peak of the pandemic, we never used more than % of our icu or ventilator capacity specifically for covid- patients. that's in part because our experience was different than many places like new york or detroit or chicago, but we prepared and asked, 'how can we deploy resources? how can we make sure that anything that could be also used like a ventilator was available?' the other thing that changed is our knowledge about how to treat covid- evolved over months. so this is a virus no one knew anything about before december/january, and in the beginning, we thought that if you waited too long to begin ventilator therapy that people would do worse, and so in the first month of the experience, we had a very low threshold to begin people on mechanical ventilation. then we learned that maybe that wasn't the best answer, so we got better at it at the same time that things were beginning to peak." given the high mortality with mechanical ventilation, alternatives are attractive. dr. spiegel reported that noninvasive ventilation by high-flow nasal cannula outperforms ventilators, and "prevent the vent" has become his department's byword. "there is literature out there," he said, supporting the high-flow nasal cannula approach , despite concerns over aerosolization, droplet transmission, and viral exposure to staff. , his ed limits high-flow nasal cannula use to "rooms that have negative pressure and have an anteroom, so that we have an area to safely don and doff our ppe without spreading that virus." beginning with anterooms, the facilities group doubled this capacity within hours, along with adding negative-pressure rooms on floors. regarding space constraints making zone separation difficult, dr. spiegel pointed to outside-the-box improvisations. "waiting rooms in an outdoor setting would be ideal ventilationwise"; tents as a covid/ influenza-like illness waiting area combine shade and fresh air. some spaces can be repurposed: "we've converted our ambulance bay into one of our hot treatment zones, and then we set up tents for the ambulance arrivals out on the street, so basically the ambulances are pulling over to the curb, taking patients out, and then bringing them to us underneath canopies." administrative hallways have served as waiting rooms when air flow is appropriate. lower-volume, higher-acuity, systemic vulnerability q t elehealth, several commentators agree, is a timely technology for screening patients and making sure ed visits are essential ones. dr. spiegel's hospital is launching a telehealth service; dr. conroy's has a virtual urgent care system in place for face-to-face evaluation and consultation. dr. yealy noted that at his institution, a few months into their telehealth operation, "we had a decade of growth happen in weeks once covid- happened, because people.had few other real options outside of coming to the ed. the regular channels were off, and they had a lot of fear about it. our telehealth volumes, whether they're scheduled or unscheduled visits, went up multiple orders of magnitude, and it's come off from the peak, but it hasn't gone back to the pre-covid era, and i don't think it ever will." the pandemic is likely to transform patterns of resource use, admission, and other system variables in unforeseen ways. ed visits declined significantly throughout the health care system during the spring peak, [ ] [ ] [ ] and dr. spiegel cautioned against a response that might make sense managerially but not medically. "i think most eds did see a decline of volume, and then we had a corresponding increase in acuity, so as the volumes went down, the patients that were presenting seemed to be sicker," he observed. "in terms of being prepared, cutting staff and reducing shifts may seem like the obvious thing to do with the simple decrease of volume, but i think that eds need to take into consideration the acuity, because as that acuity (at least in our shop) increased, the workload didn't change significantly as you would have expected." volumes have begun returning to the university of chicago's ed. whether covid- will augment them with a second wave is uncertain, but seasonal respiratory problems are inevitable, with obvious consequences for the influenza-like illness/covid hot zone if the wave appears. "especially later this year, as influenza resurges, that's probably the worst-case scenario, having multiple highly contagious respiratory illnesses," dr. spiegel said. "we may have put our rifles on safety, but we're not putting them away right now." still, the suspicion that too many exhausted, frustrated people will rush back to places of assembly, imprudent, proximate, and unmasked-in other words, that deferred gratification, trust in the scientific process, and regard for the greater good are relatively scarce concepts in current american culture what activities are safe as the coronavirus continues to spread covid- : data preliminary estimate of excess mortality during the covid- outbreak new yorkers flattened the curve. now they're dropping their guard national center for immunization and respiratory diseases (ncird); division of viral diseases. commercial laboratory seroprevalence survey data actual coronavirus infections vastly undercounted, cdc data shows antibody tests for identification of current and past infection with sars-cov- variation in false-negative rate of reverse transcriptase polymerase chain reaction-based sars-cov- tests by time since exposure treatment of ards with prone positioning high-flow nasal cannula for covid- patients: low risk of bio-aerosol dispersion high flow nasal cannula (hfnc) use in covid- respiratory failure. society of critical care medicine covid- rapid resource center (online video) high-flow nasal cannula may be no safer than noninvasive positive pressure ventilation for covid- patients ventilation techniques and risk for transmission of coronavirus disease, including covid- : a living systematic review of multiple streams of evidence impact of the covid- pandemic on emergency department visits-united states admissions to veterans affairs hospitals for emergency conditions during the covid- pandemic potential indirect effects of the covid- pandemic on use of emergency departments for acute lifethreatening conditions-united states america fails the marshmallow test key: cord- -mmz vn q authors: price, sarah; spencer, anne; zhang, xiaohui; ball, susan; lyratzopoulos, georgios; mujica-mota, ruben; stapley, sal; ukoumunne, obioha c; hamilton, willie title: trends in time to cancer diagnosis around the period of changing national guidance on referral of symptomatic patients: a serial cross-sectional study using uk electronic healthcare records from – date: - - journal: cancer epidemiol doi: . /j.canep. . sha: doc_id: cord_uid: mmz vn q background: uk primary-care referral guidance describes the signs, symptoms, and test results (“features”) of undiagnosed cancer. guidance revision in liberalised investigation by introducing more low-risk features. we studied adults with cancer whose features were in the guidance (“old-nice”) or were introduced in the revision (“new-nice”). we compared time to diagnosis between the groups, and its trend over — . methods: clinical practice research datalink records were analysed for adults with incident myeloma, breast, bladder, colorectal, lung, oesophageal, ovarian, pancreatic, prostate, stomach or uterine cancers in / / – / / . cancer-specific features in the year before diagnosis were used to create new-nice and old-nice groups. diagnostic interval was time between the index feature and diagnosis. semiparametric varying-coefficient analyses compared diagnostic intervals between new-nice and old-nice groups over / / – / / . results: over all cancers (n = , ), median (interquartile range) old-nice diagnostic interval rose over – , from ( – ) to ( – ) days, with increases in breast ( vs days), lung ( vs days), ovarian ( · vs days), prostate ( vs days) and stomach ( · vs days) cancers. median new-nice values were consistently longer ( , – in vs , – days in ) than old-nice values over all cancers. after guidance revision, new-nice diagnostic intervals became shorter than old-nice values for colorectal cancer. conclusions: despite improvements for colorectal cancer, scope remains to reduce diagnostic intervals for most cancers. liberalised investigation requires protecting and enhancing cancer-diagnostic services to avoid their becoming a rate-limiting step in the diagnostic pathway. early cancer detection is central to improving outcomes [ ] . most early-detection strategies focus on the timely recognition and investigation of people likely to have undiagnosed cancer [ ] [ ] [ ] . as screening detects < % of cancer [ ] , uk strategies focus on promptly recognising the symptoms, signs or test results associated with undiagnosed cancer ("features of possible cancer", or simply "features") [ ] . in , uk suspected-cancer guidance was published, listing features warranting cancer testing or investigation [ ] . the guidance was revised in for ovarian cancer [ ] , and in for remaining cancers [ ] . the aim was to expedite cancer diagnosis by lowering the risk of undiagnosed cancer warranting clinical action from ≥ % to % [ ] , which was achieved by introducing more vague features into the guidance [ , ] . the revised guidance is officially applicable in england, and endorsed in wales and northern ireland [ ] . our objective was to explore the timeliness of cancer diagnosis in england, wales and northern ireland in - for common internal cancers. we compared time from first feature to diagnosis between two groups: "old-nice" (with features of possible cancer in the original guidance) and "new-nice" (only participants with features introduced during guidance revision). we hypothesised that times to diagnosis would be longer for new-nice than for old-nice participants, because diagnosing cancer is more challenging and may take longer when symptoms are vague [ , [ ] [ ] [ ] [ ] . we also hypothesised that the difference in time to diagnosis between new-nice and old-nice groups would reduce over time, as evidence on vague cancer features emerged and was translated into practice by guidance revision [ , ] . this serial, cross-sectional, primary-care study used uk clinical practice research datalink (cprd gold) with linked national cancer registration and analysis service (ncras, set ) data. cprd gold comprises prospective, coded, and anonymised medical records from > uk general practices, with having ncras linkage [ ] . the study examined participants in the year before their cancer diagnosis between and . inclusion criteria: • scotland, where separate guidance applies [ ] . • multiple primary cancers. • cancer typical of the opposite sex; e.g. male breast cancer. • screen-detected cancer, identified from ncras or by cprd screening codes in the year before diagnosis. • no primary care attendance or no recorded feature of the participant's cancer in the year before diagnosis. . . . features of possible cancer cprd codes for features of possible cancer were collated [ ] , based on the symptoms, signs or blood test results in the original or revised guidance (table ) [ , , ] . occurrences of these codes, restricted to the relevant cancer site, identified participants presenting with these features in the year before diagnosis. separate generic "suspected-cancer" codes were identified to explore for changing recording practices. the cancer diagnosis date was the earliest cprd or ncras diagnostic code. the first recorded feature of possible cancer (index feature) was identified, along with the index date. our outcome variable was "diagnostic interval": days from index date to diagnosis [ ] . participants were grouped by their index feature(s) (fig. , table ): • old-nice: participants with ≥ index feature from the guidance [ ] . • new-nice: limited to participants who only had index feature(s) introduced during guidance revision [ , ] . participants whose only index feature was a generic "suspectedcancer" code were omitted from analyses. age and sex were identified from the cprd year of birth, assigning a birthday of st july. simple descriptive statistics summarised age (mean and standard deviation), sex (male, n, %), nice grouping (new-nice group, n, %), and the index feature(s) (n, % of all index features). we summarised diagnostic interval using mean (standard deviation) and the th, th, th, and th centiles. diagnostic interval has a skewed distribution and was log-transformed for analyses [ ] . semiparametric varying-coefficient methods estimated coefficients representing the percentage difference in mean log-transformed diagnostic interval between new-nice and old-nice groups (see accompanying methodological paper [ ] ). a coefficient of represents no difference between the nice groups. positive coefficients indicate that diagnostic intervals are longer for the new-nice than the old-nice group; negative coefficients, that they are shorter. the coefficients are estimated on a daily basis, so cannot be reported using a single summary statistic, and are plotted (with % confidence intervals, using bootstrapping, n = replications [ ] ) to allow visualisation over - . the models adjusted for age and sex. analyses examined each cancer site separately, sample size permitting (package "np" in r) [ ] . numbers of potential inclusions (individual diagnoses), with cancer registry linkage, and exclusions, to give final sample sizes by cancer site. the final sample is described in terms of size (n), age (mean, sd), number (%) who are male, and number (%) with an index cancer feature introduced during guidance revision. for the descriptive statistics, we included all cprd participants meeting our inclusion criteria. semiparametric varying-coefficient analyses were limited to cancer sites with participant numbers providing ≥ % power at the % level to detect a -day difference in diagnostic interval between new-nice and old-nice groups. assuming mean diagnostic intervals of and days, respectively, for the old-nice and new-nice groups, a common standard deviation of days and % of participants classified as new-nice requires total participants. an effect size of days matches the two-week-wait target for urgent investigation. we assessed uncertainty in the estimates by confidence interval width. to explore for potential bias associated with changing coding practice, we identified, for annual cohorts: (a) the percentages of participants excluded for having no coded features or only suspected-cancer codes; (b) the proportions of old-nice and new-nice participants; (c) demographic characteristics of participants excluded because they lacked coded features. the cprd provided , participants, of whom , ( ⋅ %) were excluded, leaving , ( ⋅ %) entering the analyses, from practices, of which ( ⋅ %) had ncras linkage ( table ). the main reasons for exclusion were lack of recorded features (n = , ), scottish residence (n = , ) and detection following screening (n = ) (fig. ) . the sex distributions indicate male dominance in bladder ( / , ⋅ %), oesophageal ( / , ⋅ %) and stomach ( / , ⋅ %) cancers ( table ). the overall mean (sd) age at diagnosis (n = , ) was ⋅ years ( ⋅ ), ranging from ⋅ years ( ⋅ ) for breast to ⋅ years ( ⋅ ) for stomach (table ) . the percentage of participants whose index feature was introduced during guidance revision (new-nice group) varied by cancer, ranging from / ( ⋅ %) for myeloma to / , ( ⋅ %) for breast. more even distributions were observed for colorectal ( / , , ⋅ %), lung ( / , , ⋅ %), ovarian ( / , ⋅ %), and uterine ( / , ⋅ %) cancers (table ). ( / , ⋅ %). postmenopausal bleeding accounted for nearly half of all index features of uterine cancer ( / , ⋅ %), with lower frequencies for high blood glucose ( / , ⋅ %) and low haemoglobin ( / , ⋅ %). overall, the median diagnostic interval was days (interquartile range (iqr) - , n = , ). by cancer site, the shortest diagnostic interval was in breast (median, iqr: , - days, n = , ) and the longest in lung (median, iqr: , - days, n = , ) ( table ) . median (interquartile range) diagnostic intervals by year and by nice grouping are plotted in fig. fig. ). median diagnostic intervals were longer for new-nice than for old-nice participants for colorectal ( vs days), oesophageal ( vs days), and lung ( ⋅ vs days) cancers; however, this difference tended to decrease or disappear over time (fig. ) . in ovarian cancer, diagnostic intervals were shorter in the new-nice than in the old-nice group overall ( vs days), notably in - (fig. ) . for bladder, colorectal, oesophageal, pancreatic and uterine cancers, median old-nice diagnostic intervals remained constant over - . they were longer in compared with for breast ( vs days), lung ( vs days), ovarian ( vs ⋅ days), prostate ( vs days) and stomach ( vs ⋅ days) cancers (fig. ) . semiparametric varying-coefficient analyses were powered for bladder, breast, colorectal, lung, prostate and uterine cancers. the percentage differences (with % confidence intervals) in mean logtransformed diagnostic interval between new-nice and old-nice groups over time are plotted in fig. . after guidance revision on rd june , new-nice diagnostic intervals tended to shorten relative to those of the old-nice group in prostate (fig. e) and uterine (fig. f) cancers (note the downward trajectory towards the horizontal dashed line). for colorectal cancer, the difference in diagnostic interval between the new-nice and old-nice groups reduced over time. after guidance revision, new-nice diagnostic intervals were shorter than old-nice intervals, as indicated by the trend dropping below the horizontal dashed line (fig. c) . for lung cancer, new-nice were longer than old-nice diagnostic intervals in the years - . in - , there was no difference between the groups. in (post guidance revision), new-nice diagnostic intervals shortened relative to old-nice diagnostic intervals, but this was not sustained into - (fig. d) . the proportions of eligible participants excluded for lack of coded features increased over time for bladder, colorectal, lung, oesophageal, ovarian, pancreatic, stomach, and uterine cancers. this coincided with increased use of suspected-cancer codes (fig. s ) . the demographic details of excluded and included participants were similar (table s and table ). the proportions of old-nice and new-nice participants were largely similar across time within cancer sites (fig. s ). this study examined diagnostic intervals for cancers in england, table diagnostic interval ( th, th, th, and th centiles, mean and standard deviation) by cancer site. wales and northern ireland over - , a period including major revision of national suspected-cancer referral guidance. as hypothesised, times to diagnosis were generally longer for "new-nice" participants (with index feature(s) of cancer introduced during guidance revision) than for "old-nice" participants (with feature(s) in the original guidance). importantly, for colorectal cancer, new-nice diagnostic intervals were shorter than old-nice diagnostic intervals after guidance revision. the gap between new-and old-nice groups decreased for prostate and uterine cancers over time, consistent with decreasing new-nice diagnostic intervals aided by increasing old-nice diagnostic intervals for prostate cancer. the revised national guidance and gp responses to its preceding evidence base may have contributed to these changes, along with other early-diagnosis initiatives. in conclusion, scope remains to reduce time to diagnosis for symptomatic cancers in england, wales and northern ireland. a considerable strength is the study's primary-care setting, where suspected-cancer guidance is implemented. the cprd is the largest primary-care database worldwide and is recognised for its high-quality data [ ] . we used established methods for case identification [ ] , with validation of cancer diagnosis by ncras where linkage was available. ncras data completeness improved in [ ] . pre- studies report a concordance rate of ⋅ % between cprd and cancer registry information [ ] . the cprd diagnosis date was a median of days (interquartile range - to days) later than the registry date pre- for colorectal, lung, gastrointestinal, and urological cancers [ ] . thus pre- diagnostic intervals may be overestimated compared with post- values. reassuringly, no step-change in newor old-nice diagnostic intervals were observed around , suggesting that any associated bias is small. we studied diagnostic interval rather than the primary care (time from index date to referral) or secondary care (time from referral to treatment) interval to avoid restricting analyses to participants referred to secondary care [ ] . a limitation was the inability to analyse diagnostic intervals separately for participants referred via the two-week-wait pathway [ ] because robust data sources for identifying them were unavailable to us. we found conflicting evidence of changes in gp recording practice over time. the proportion excluded for lack of coded features increased over time for some cancers, often coinciding with increased use of "suspected-cancer" codes. the proportions of old-and new-nice groups over time were constant and the similar demographic details for included and excluded participants suggests no marked selection bias. we excluded approximately % of participants for lack of coded features, a proportion consistent with evidence that coded cprd data identifies % of visible haematuria or jaundice events, and - % of abdominal pain in patients with pancreatic or bladder cancers [ ] . of participants without recorded features, some will have presented at emergency departments without prior primary-care consultations [ , , ] , some will had the information recorded in "free text" [ ] , and others may have presented with features outside nice guidance. such features were deliberately omitted from our study, as irrelevant to our focus on guidance revision. our analytical method allowed us to explore trends in the difference in diagnostic interval between groups aligned by their index feature(s) to the revised (new-nice) or original (old-nice) guidance [ ] . the method was derived to explore the time-varying and gradual impact of emerging clinical evidence that is legitimised into clinical practice by official guidance revision and implementation [ ] . our findings build on previous analysis of the original nice guideline's impact on diagnostic interval [ ] . mean diagnostic interval for uk cancers reduced between - and - by ⋅ days ( % ci: ⋅ - ⋅ days) from an initial value of ⋅ days. similar to our study, median diagnostic intervals were shortest for cancers commonly presenting with lumps/masses (e.g. days for breast) and longest for cancers often presenting with symptoms shared with other diseases (e.g. days in lung cancer) [ ] . our estimates of diagnostic interval for colorectal cancer are similar to those obtained by the international cancer benchmarking partnership using different data sources [ ] . our findings are consistent with the taxonomy of cancer symptom "signatures" and diagnostic difficulty [ ] . breast cancer had a narrow signature of a single alarm feature (breast lump) highly predictive of undiagnosed cancer plus the shortest diagnostic interval. in contrast, lung cancer had a very broad signature and the longest diagnostic interval. jensen et al. [ ] investigated the impact of implementing a standardised cancer patient pathway in denmark in - . post-implementation diagnostic intervals were ( ) ( ) ( ) ( ) ( ) ( ) days shorter than peri-implementation values for the % of patients actually referred via a cancer pathway, but were ( - ) days longer for the % of patients diagnosed via other routes. the authors concluded that the cancer pathways expedited diagnosis for a minority of patients. the relationship between diagnostic interval and mortality (and stage) is u-shaped, reflecting confounding by indication [ ] [ ] [ ] . patients with advanced tumours generally receive an expedited diagnosis (possibly as an emergency) and have poor outcomes because of their high inherent mortality: the so-called "sick-quick". conversely, patients presenting with vague symptoms usually have longer diagnostic intervals, and higher mortalitythought to reflect the impact of diagnostic delay, particularly between referral and diagnosis [ ] [ ] [ ] [ ] . the revised guidance aimed to benefit patients by legitimising doctors to investigate at a lower risk of undiagnosed cancer. this change can reduce both diagnostic delay and emergency presentation. in this study, for colorectal cancer, new-nice diagnostic intervals reduced relative to old-nice interval after guidance revision. this is consistent with general practitioners acting on the vague ("new-nice") features introduced during guidance revision. indeed, the proportion diagnosed via the urgent cancer referral pathway increased from % ( %ci %- %) in to % ( %- %) in , spanning the period of guidance revision [ ] . our findings of increasing old-nice diagnostic intervals over time may reflect growing strain on nhs diagnostic-endoscopy and imaging services [ ], as demand for all indications (not just cancer) rises [ ] , particularly if ct-based targeted screening for lung cancer is introduced [ ] . in , inadequate diagnostic capacity was considered a rate-limiting step in the diagnostic pathway [ ] , and a negative impact of covid- on diagnostic services is already becoming apparent [ ] . we conclude that scope remains to reduce time to cancer diagnosis. the revised colorectal cancer diagnostic guidance may be exerting a downward pressure on time to diagnosis of this cancer, through impacts on the vague features of cancer introduced during guidance revision. future studies using causal analysis should examine the impact of guidance revision on staging at diagnosis and survival for all cancers, and the possible downstream effects on investigative services. policymakers are urged to enhance cancer diagnostic services so that they do not pose a rate-limiting step in the diagnostic pathway, and to protect them from the pressures of covid- . this study was funded by cancer research uk [c /a ], who were not involved in any aspect of the conduct of the study, in writing the manuscript or in the decision to submit for publication. this research is also linked to the cantest collaborative, which is funded by cancer research uk [c /a ], of which wh is co-director, gl is associate director, as is senior faculty, and sp is an affiliated research wh was clinical lead of the guideline development group which formulated the revised nice suspected-cancer guidelines (ng ). this paper is written in a personal capacity and is not to be interpreted as representing the views of the group or of nice. the remaining authors report no declarations of interest. achieving world-class cancer outcomes: taking the strategy forward suspected cancer: recognition and referral cancer patient pathways in denmark as a joint effort between bureaucrats, health professionals and politicians-a national danish project the national cancer program in sweden: introducing standardized care pathways in a decentralized system routes to diagnosis the expanding role of primary care in cancer control national institute for health and clinical excellence, referral guidelines for 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implementation of cancer patient pathways -a gp survey and registry based comparison of three cohorts of cancer patients is omission of free text records a possible source of data loss and bias in clinical practice research datalink studies? a case-control study emergency diagnosis of cancer and previous general practice consultations: insights from linked patient survey data does emergency presentation of cancer represent poor performance in primary care? insights from a novel analysis of linked primary and secondary care data diagnostic routes and time intervals for patients with colorectal cancer in international jurisdictions; findings from a cross-sectional study from the international cancer benchmarking partnership (icbp) guideline-concordant timely lung cancer care and prognosis among elderly patients in the united states: a population-based study diagnostic interval and mortality in colorectal cancer: u-shaped association demonstrated for three different datasets variation in 'fast-track' referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from patients with cancers of different sites advanced-stage cancer and time to diagnosis: an international cancer benchmarking partnership (icbp) cross-sectional study national cancer registration and analysis service: routes to diagnosis scoping the future: an evaluation of endoscopy capacity across the nhs in england targeted screening for lung cancer with low radiation dose computed tomography unfinished business: an assessment of the national approach to improving cancer services in england cancer diagnosis and treatment in the covid- era supplementary material related to this article can be found, in the online version, at doi:https://doi.org/ . /j.canep. . . key: cord- -wjdmzmdg authors: bashir, muhammad farhan; ma, benjiang; bilal; komal, bushra; bashir, muhammad adnan; tan, duojiao; bashir, madiha title: correlation between climate indicators and covid- pandemic in new york, usa date: - - journal: sci total environ doi: . /j.scitotenv. . sha: doc_id: cord_uid: wjdmzmdg this study analyzed the association between covid- and climate indicators in new york city, usa. we used secondary published data from new york city health services and national weather service, usa. the climate indicators included in the study are average temperature, minimum temperature, maximum temperature, rainfall, average humidity, wind speed, and air quality. kendall and spearman rank correlation tests were chosen for data analysis. we find that average temperature, minimum temperature, and air quality were significantly associated with the covid- pandemic. the findings of this study will help world health organization and health regulators such as center for disease control (cdc) to combat covid- in new york and the rest of the world. • the study examines the impact of climate indicators on covid- epidemic in new york city. • average temperature, minimum temperature and air quality have significant correlation with covid- epidemic. • currently there is no scientific evidence that warm weather would suppress covid- epidemic. a b s t r a c t a r t i c l e i n f o on december , , the world health organization (who) reportedly received information about an epidemic with unidentified etiology (deepak et al., ) from wuhan, hubei, china (zhu et al., ) . on february , , this epidemic was officially named as covid- and was acknowledged as an infectious disease resulting in public health emergency, as it quickly spread within china and to further countries is situated geographically between . °n and − . °e (anderson et al., ) . clinical studies relating to covid- reported that most patients suffer from difficulty in breathing and pneumonia (holshue et al., ; perlman, ) . symptoms reported in clinical treatments were similar to other coronavirus illnesses such as mers and sars e.g. cough, fever, and difficulty in breathing due to respiratory disorder, and in worst-case scenario covid- causes kidney failure, pneumonia, and even death . in the usa, the first covid- patient was reported in the washington state on january , , and coronavirus quickly spread throughout the country as the usa became the epicenter with most deaths and the most number of patients or cases which are seen on map in fig. . and after wisconsin reported its first death on april , , all states had at least one casualty from covid- in the usa. as of april , new york ( , ) , florida ( , ) and new jersey ( , ) are worst-hit states in america. new york state quickly became epicenter within the usa with the majority of cases and deaths reported in new york city, which reported its first case on march , , and after initial days saw a rapid rise in the number of patients and deaths from march , , onwards. similar quick spread of covid- in italy, france, and south korea, led to who declaring it as a pandemic (cucinotta and vanelli, ) . current studies have shown that the transmission route of covid- is bat-human, with intermediate host yet to be identified; it was transmitted mainly by respiratory droplets, as well as human-human transmission (ge et al., ; huang et al., ) . climate conditions are classified as top predictors of coronavirus illnesses (dalziel et al., ) as wind speed, humidity, temperature and wind speed are critical in the transmission of infectious diseases (yuan et al., ) . bull ( ) reported that pneumonia's mortality rate is highly correlated with weather changes. new york city is the capital of new york state and is described as media, cultural and financial hub of the world. new york is one of the densely populated cities in the usa with . million people residing within . squares miles and is situated geographically between . °n and − . °e. dataset for covid- is taken from march , -april , , from covid- data archive from the new york city health department. and data for climate indicators was taken from national weather service, usa. dataset for the climate indicators includes temperature, humidity, wind speed, air quality, and rainfall. as the data was not normally distributed therefore kendall and spearman rank correlation tests were utilized to examine the correlation between variables. fig. observes a sharp increase, both in daily new cases and total confirmed cases for new york city from march , , onwards. the first week beginning from march , to march , , confirmed cases are , which rose to until the second week on march , , , until the end of third week, , until the fourth week, , until the fifth week on april , and , until april , . fig. shows the maximum, minimum, and average temperature. lowest maximum temperature of °f (highest maximum °f), lowest average temperature was . °f (maximum average . °f) and the minimum lowest temperature was °f (highest lowest °f), average lowest wind speed . mph (maximum average . mph), average lowest humidity . % (highest average humidity . %) and average lowest rainfall mm (average highest rain fall is . mm) are the statistical indicators of new york city. table indicates empirical estimations of seven weather indicators. for kendal correlation test minimum temperature and average air quality are significant for new cases, and average temperature, minimum temperature, and average air quality are significant for total cases and average temperature and air quality are significant for mortality among new york citizens. for the spearman test, average temperature and average air quality are significant for new cases and average temperature and average air quality are significant for the total number of cases, also average temperature and air quality are significant for mortality. for the current research project, the occurrence of covid- in new york city is analyzed by climate change patterns. our findings estimate that minimum temperature and average temperature are correlated with the spread of covid- in new york city. previous studies of tan et al. ( ) and vandini et al. ( ) support our findings. shi et al. ( ) also researched climate indicators and stated that temperature serves as a driver for the covid- . as a cultural and financial capital of the world, new york city also oversees high mobility from local as well as constituents from other major places to seek employment and business opportunities. humidity is another contributor for the spread of covid- as it contributed in the rapid transmission within new york city and empirical estimations of this study will be useful in the outcome of efforts to suppress covid- . according to official census data, new york city is resident to . million people with population increasing at . % per year and , residents living per square mile. the reason for such a dense population is the average life expectancy of new york residents, which is . years, this is . years longer than the national average of life expectancy in america. such statistics make new york an ideal epicenter for the spread of infectious diseases (zu et al., ) . humidity and temperature also play significant role in the seasonal spread of coronaviruses (sajadi et al., ) . wang et al. ( ) also reported similar findings for the case of china. covid- outbreak from wuhan showed a strong association between disease spread and weather conditions, with predictions that warm weather will play an important role in suppressing the virus. other meteorological indicators such as wind speed, air quality, and humidity also affect the spread of infectious diseases. furthermore, air temperature also contributes towards the transmission of the virus . ma et al. ( ) suggested that humidity and temperature will play an important role in mortality rate from covid- as climate indicators and temperature correlate with the spread of covid- (poole, ) . this study, despite strong evidence of climate indicators' association with covid- , provides the following limitations. first, more variables are needed to conduct a comprehensive study as covid- is an infectious disease and it is affected by many variables such as social distancing, people's endurance and availability of health facilities. second, data about personal hygiene indicators such as hand wash needs to be explored in further studies. climate indicators are integral in the fight against covid- in new york. this study finds that average temperature, minimum temperature, and air quality are significant correlated with covid- pandemic and will be useful in suppressing covid- . also, significance of air quality implies that green environment policies should be promoted as it would reduce the spread of infectious diseases such as covid- . current study is of exploratory nature and in order to conduct a comprehensive investigation, future research direction should examine daily carbon emission data as current lockdown measures have greatly reduced carbon emissions. another research direction is to include regional and cross-country investigations for most affected countries to provide better insight for the fight against covid- . we acknowledge the financial support by the ministry of education-china mobile joint laboratory grant number: mhl . authors would also like to acknowledge the editors and two anonymous reviewers, who contributed immensely in improving the quality of this publication. how will country-based mitigation measures influence the course of the covid- epidemic? the weather and deaths from pneumonia roles of meteorological conditions in covid- transmission on a worldwide scale who declares covid- a pandemic urbanization and humidity shape the intensity of influenza epidemics in u covid- for the cardiologist: a current review of the virology, clinical epidemiology, cardiac and other clinical manifestations and potential therapeutic strategies isolation and characterization of a bat sars-like coronavirus that uses the ace receptor first case of novel coronavirus in the united states clinical features of patients infected with novel coronavirus in wuhan effects of temperature variation and humidity on the mortality of covid- in wuhan another decade, another coronavirus seasonal influences on the spread of sars-cov- (covid ), causality, and forecastabililty ( - - ) temperature and latitude analysis to predict potential spread and seasonality for covid- the impact of temperature and absolute humidity on the coronavirus disease (covid- ) outbreak evidence from china an initial investigation of the association between the sars outbreak and weather: with the view of the environmental temperature and its variation respiratory syncytial virus infection in infants and correlation with meteorological factors and air pollutants unique epidemiological and clinical features of the emerging novel coronavirus pneumonia (covid- ) implicate special control measures a climatologic investigation of the sars-cov outbreak in beijing a novel coronavirus from patients with pneumonia in china coronavirus disease (covid- ): a perspective from china. radiology key: cord- -e md ein authors: mcleod, melissa; gurney, jason; harris, ricci; cormack, donna; king, paula title: covid‐ : we must not forget about indigenous health and equity date: - - journal: aust n z j public health doi: . / - . sha: doc_id: cord_uid: e md ein nan a s new zealand's cases of covid- rapidly rose, a national state of emergency was declared and the country placed in shutdown in an effort to achieve disease elimination. however, a looming crisis of māori (indigenous peoples of new zealand) health and equity appeared to have had little attention from decisionmakers should our elimination strategy fail. there is major concern among those working in māori health about the disproportionately negative impact a covid- pandemic is likely to have on māori communities in the event of widespread illness (www.uruta. maori.nz) -concerns that are relevant to indigenous communities globally. in this paper we discuss risk to māori and the need to consider māori health equity in all levels of decision-making and in all strategies aimed at mitigating the impact of an overwhelming covid- outbreak. the themes within this call to action are immediately transferable to other future pandemic crises and to the underlying and longstanding crisis of embedded ethnic health inequities for indigenous peoples. history warns us of the price of assuming that diseases such as covid- will impact ethnic groups evenly. the death rate following the influenza pandemic was seven times higher for māori compared to european ethnic groups. more recently during the h n influenza pandemic, disease rates were twice as high for māori compared to european/other, while māori were three times as likely to be hospitalised with the disease and nearly three times as likely to die. inequities in disease rates and mortality during the h n influenza pandemic were seen for indigenous populations in australia and canada. , these inequitable outcomes, in part, reflect differences between indigenous and non-indigenous populations in factors that increase communicability of infectious diseases. in new zealand, such factors include social deprivation, the quality of housing, fuel and heating, poverty and household crowding. [ ] [ ] [ ] the latter is crucial with respect to disease transmission among māori: one in every five māori live in overcrowded housing, compared to only one in nz european/ pākehā. combined, these factors manifest in substantial inequities in rates of most infectious diseases, including influenza, meningococcal disease, tuberculosis and the sequelae of streptococcal infection such as rheumatic fever. differences in factors relating to living conditions and crowding are poignant in the context of covid- . in italy, it has been hypothesised that intergenerational interactions and co-residence may have contributed to the rapid spread of sars-cov- . evidence from china suggests that the vast majority of transmission has occurred through families within households ( - % of cases). in singapore, outbreaks occurred among migrant workers living in overcrowded conditions with limited access to sanitation, resources and power to complain. in the new zealand context, this means that because of differences in living conditions, māori will be more likely to be exposed to sars-cov- than nz european/pākehā. for example, universal recommendations of home-isolation for mild cases may well lead to differential household transmission among families living in more crowded conditions, with higher risk for those in multi-generational households. internationally, racial/ethnic inequities in rates of infection have been identified. higher infection rates have been shown for indigenous communities, including for example, native hawaiian and pacific peoples in some states of the us and the navajo nation. , the health impact of covid- will be greater for māori the severity of covid- illness -and subsequent risk of death -is increased among those with underlying health conditions such as cardiovascular, cancer, pulmonary, renal and endocrine comorbidity. [ ] [ ] [ ] it follows that those population groups with a greater likelihood of living with these conditions stand to experience the greatest impact of covid- on health and mortality. we, as māori, are substantially more likely to have all comorbidities relevant to covid- ( figure ) and thus will experience a significant disproportionate burden of serious covid- outcomes compared to european ethnic groups. in addition to a greater overall burden of relevant comorbidities, the age at which these comorbidities occur is also different for māori ( figure ). without exception, these important chronic conditions occur earlier in life for māori: we get sicker, younger. this is highly relevant to discussions of age cut-offs when prioritising health care (see section below). a little-understood factor also at play is the impact on covid- outcomes where several of these relevant conditions are occurring at once. if one of these relevant conditions can impact outcomes, it is likely that multiple conditions will have a compounding effect -possibly additive, but potentially multiplicative. crucially, māori are much more likely to have multimorbidity than those from european ethnic groups ( figure ). the reported case fatality rates from covid- show a strong gradient by age, with those aged over years demonstrating the highest rates. it may therefore be assumed that indigenous populations, by virtue of our younger age structure, are role in the creation and maintenance of inequities in health for indigenous populations. it has been estimated that a quarter of the absolute difference between māori and non-māori in all-cause mortality was the result of conditions considered amenable to healthcare. existing inequities in healthcare access may lead to differences in covid- detection. new zealand is currently seeing very small numbers of covid- cases with the focus currently on early detection and rapid management of cases and contacts. , however, potential inequities in access to testing could lead to a higher risk of undetected cases as demonstrated in a recent modelling paper. the authors highlight the particular risk for māori and pacific communities where there are known inequities in access to primary care. existing inequities in healthcare access will be amplified when the system is put under pressure. in new zealand, despite a wide package of publicly-funded secondary and tertiary healthcare, and primary care being subsidised by the government, there are significant ethnic inequities in access to healthcare. the greatest identified barrier to healthcare is financial. māori report higher rates than non-māori of unmet need for healthcare, including unmet need for gp and afterhours care and unfilled prescriptions. māori also experience greater rates of hospitalisation for conditions that are either avoidable (through health and injury prevention strategies) or amenable (through appropriate healthcare). there is also evidence across a range of diseases of a lower quality of care being provided to māori compared with non-māori. in addition, institutionalised racism impacts māori health and inequities through the underlying values and structuring of our health system, figure : age-specific rates of (for example) congestive heart failure (left) and chronic pulmonary disease (right), for māori and european ethnic groups. figure : age-specific rates of (for example) congestive heart failure (left) and chronic pulmonary disease (right), for māori and european ethnic groups. age-specific rates: chronic pulmonary disease māori european relatively protected from high case fatality from covid- , however, such an assumption is a mistake. age is more than just a number. while there is no denying that age is an important predictor of outcomes for those diagnosed with covid- , it is unclear as to the mechanism by which age acts as a risk factor. if older age is a risk factor because those in older age groups have a higher burden of health conditions that increase risk (such as cardiovascular and respiratory disease), age will not be protective for younger indigenous populations. as discussed above, the rates of many health conditions for māori are similar to nz european rates - years earlier, which contributes to the lower life expectancy and healthy life expectancy of indigenous populations compared to our non-indigenous counterparts. if age is a risk factor independent of comorbid conditions, it may still operate differently for māori with evidence of processes of accelerated aging at the cellular level in those more likely to experience racism. strong public messaging of age as the primary risk factor does not allow indigenous populations to adequately prepare and respond. initial evidence of the relative importance of age versus comorbidity for covid- severity was unclear. , more recently, a large uk study showed that increased age and comorbidity were independently associated with risk of hospital death from covid- , as was non-white ethnicity. more appropriate public messaging would identify indigenous populations as at increased risk of severe impacts, and messages should be extended to include younger indigenous populations. differential access to health care as a result of colonisation and racism plays an important while individual level racism from health professionals is disproportionately reported by māori, with evidence of health provider implicit and explicit racial/ethnic bias against māori. even where containment strategies are implemented, health services may be overloaded. without careful planning, the reductions in access and quality of care over this time will differentially impact indigenous populations because the 'usual' barriers to care will be amplified -for example, through simultaneous increased unemployment and financial hardship. existing health provider racism is more likely to be activated in pressured situations, and tools used to decide on limited healthcare have the potential to discriminate against māori and other groups marginalised by oppressive systems if equity is not carefully considered and embedded throughout, and if they are developed without partnership with the groups most likely to be impacted. it is unclear how other shifts in healthcare service provision during the pandemic may impact on inequities in healthcare access for māori, such as the move to provide primary care through telehealth and further primary care subsidies. for example, have these taken into account differing access to technology and appropriate communication needs? when new strategies are developed, it is important that these centre māori health and equity and are monitored in real time. reductions in healthcare access will differentially impact on indigenous populations for non-covid- outcomes for which we already have inequities. there is evidence from previous influenza pandemics of inequitable increases in all-cause mortality driven by deaths from influenza but also from an increase in other health events, in part due to reductions in access to care. we have focused on the implications of increased disease transmission, risk of severe disease and healthcare for māori in this report. however, a covid- epidemic and the actions to eliminate or mitigate it, have far-reaching social and economic consequences that are likely to disproportionately impact māori whānau and communities and exacerbate social and health inequities. health and welfare implications related to multiple issues such as disability, care and protection, mental health, addiction, prison health, poverty, housing and houselessness, and family violence, will all differentially affect māori. as māori researchers and health professionals, we are deeply concerned about the potential impact of covid- on māori communities. similar concerns have been expressed by other indigenous nations. , we are also concerned that there appears to be limited focus on māori health equity in the current health system and whole-of-government planning. māori communities, health workers and leaders are taking action to protect māori health and wellbeing (for example, www. uruta.maori.nz). in new zealand, the treaty of waitangi forms the foundation of the contractual relationship between māori and the british crown (represented by the state). we call for the state as treaty partner to uphold its treaty obligations and māori indigenous rights contained within the united nations declaration on the rights of indigenous peoples by acting to protect māori health and wellbeing. in partnership with māori, the state must consider māori health and equity in all actions aimed at combating and responding to a covid- pandemic, both now and beyond. in addition, real-time modelling, monitoring and rapid analysis of data using high quality ethnicity data underpinned by principles of indigenous data sovereignty, is required across multiple levels including case numbers and rates, transmission, severity and access to and quality of care (including the performance of public health responses), to inform and assess intervention strategies for māori. if māori health, and indigenous health more globally, is not given the necessary attention required now, history will repeat itself. figure : age-standardised rate ratios, comparing m multimorbidity score between māori and europeans. categories are based on multimorbidity scores, which are calculated for each patient as the weighted sum of individual morbidities. increasing score (and category) relates to increasing multimorbidity burden. age-standardised rate ratios, comparing m multimorbidity score between māori and europeans. categories are based on multimorbidity scores, which are calculated for each patient as the weighted sum of individual morbidities. increasing score (and category) relates to increasing multimorbidity burden. wellington (nz): nz government the influenza pandemic in new zealand. christchurch (nz) pandemic influenza a(h n ) in new zealand: the experience from differential mortality rates by ethnicity in influenza pandemics over a century disproportionate impact of pandemic (h n ) influenza on indigenous people in the top end of australia's northern territory incidence of hospital admissions and severe outcomes during the first and second waves of pandemic (h n ) critically ill patients with influenza a(h n ) infection in canada analysis of household crowding based on census data. wellington (nz): ministry of health a stocktake of new zealand' s housing. wellington (nz): new zealand centre for sustainable cities more than in māori and pacific people live in a damp house modelled seasonal influenza mortality shows marked differences in risk by age, sex, ethnicity and socioeconomic position in new zealand a -year serogroup b meningococcal disease epidemic in new zealand: descriptive epidemiology tuberculosis associated with household crowding in a developed country estimating the risk of acute rheumatic fever in new zealand by age, ethnicity and deprivation demographic science aids in understanding the spread and fatality rates of covid- report of the who-china joint mission on coronavirus disease geneva (che): who covid- : study shows workers worried about accommodation, access to sanitation, and wages how we are uniting: stay home. wellington (nz) this time must be different: disparities during the covid- pandemic covid- special column: covid- hits native hawaiian and pacific islander communities the hardest covid- and indigenous peoples: an imperative for action clinical characteristics of hospitalized patients with novel coronavirusinfected pneumonia in wuhan epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study cancer patients in sars-cov- infection: a nationwide analysis in china estimated inequities in covid- infection fatality rates by ethnicity for aotearoa new zealand the impact of multimorbidity on adult physical and mental health in low-and middle-income countries: what does the study on global ageing and adult health (sage) reveal? development and validation of the m index for measuring multimorbidity load for risk of mortality case-fatality rate and characteristics of patients dying in relation to covid- in italy new zealand ministry of health. mortality and demographic data health loss in new zealand: a report from the new zealand burden of diseases, injuries and risk factors study racial discrimination and telomere shortening among african americans: the coronary artery risk development in young adults (cardia) study covid- : the relationship between age, comorbidity, and disease severity -a rapid review. oslo (nor): norwegian institute of public health covid- : risk factors for severe disease and death opensafely: factors associated with covid- -related hospital death in the linked electronic health records of million adult nhs patients the answer to indigenous vulnerability to coronavirus: a more equitable public health agenda. the conversation how much does health care contribute to health gain and to health inequality? trends in amenable mortality in new zealand covid- dashboard covid- testing in alert levels and to support new zealand's elimination strategy. wellington (nz): new zealand ministry of health auckland (nz): te pūnaha matatini university of auckland centre of research excellence barriers to and delays in accessing breast cancer care among new zealand women: disparities by ethnicity new zealand health survey: annual update of key findings / . wellington (nz): ministry of health tatau kahukura: māori health chart book health quality and safety commission. a window on the quality of aotearoa new zealand's health care hauora: report on stage one of the health services and outcomes kaupapa inquiry -wai experience of racism and associations with unmet need and healthcare satisfaction: the / adult new zealand health survey ethnic bias amongst medical students in aotearoa/new zealand: findings from the bias and decision making in medicine (bdmm) study impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand under the radar: how unexamined biases in decision-making processes in clinical interactions can contribute to health care disparities too many patients…a framework to guide statewide allocation of scarce mechanical ventilation during disasters all-cause mortality during first wave of pandemic (h n ) united nations declaration on the rights of indigenous peoples te mana raraunga: māori data sovereignty network. principles of māori data sovereignty te mana raraunga we would like to acknowledge members of te rōpū whakakaupapa urutā (national māori pandemic group) for reviewing an earlier version of the paper -professor key: cord- - rsrx m authors: shulman, stanford t title: the history of pediatric infectious diseases date: journal: pediatr res doi: . / .pdr. . . sha: doc_id: cord_uid: rsrx m the history of pediatric infectious diseases closely parallels the history of pediatrics at least until the last century, because historically infections comprised the major causes of childhood morbidity and mortality, as they still do in the developing world. this history reviews developments in the field through the centuries and is writen so that it does not overlap the contribution to this series by baker and katz entitled ‘childhood vaccine development in the united states.' remarkable descriptions of selected pediatric infections existed long before the invention of printing, and early pediatric texts included many chapters devoted to various infections. coincident with the establishment of pediatric organizations in america in the late (th) and early (th) centuries, major attention was focused on diphtheria, infant diarrheal illnesses, tuberculosis, streptococcal infections and their complications, and other pediatric infections, and substantial progress was made. the american pediatric society ( ), the american academy of pediatrics ( ), the society for pediatric research ( ), and the american board of pediatrics ( ) all contributed to the evolution of the discipline of pediatric infectious disease, and numerous leaders of these organizations had significant infectious diseases interests. the establishment of the pediatric infectious diseases society, the pediatric infectious diseases sub-board, and an accreditation process for training programs, as well as sub-specialty textbooks and journal, further validated the development of this specialty, particularly in north america. the many remaining challenges related to infectious diseases in children (including hiv, emerging infections, antimicrobial resistance, opportunistic infections, and infections in the developing world) insure the future of the specialty. the genomic era of medicine and the tools of molecular biology will lead to new insights into pathogenesis, diagnosis, and treatment of infections. pediatric infectious diseases physicians can celebrate the past triumphs of the discipline and future achievements, all contributing to improved health for children. noted the complications of these illnesses; and the th century works of the prominent arab physician avicenna (ibn sina), who wrote on children's illnesses including tetanus, cough and catarrh, aphthae, ear drainage, seiriasis, fevers, pustules, throat inflammation, worms and diarrhea (flux) ( , ) . for the next almost y, there were virtually no pediatric writings. the invention of printing in the mid- th century revived learning, and the first printed work on diseases of children was published in by the italian paolo bagellardo, including chapters on many common infections, including tinea capitis, otorrhea, ear abscess, cough, rheumatism and diarrhea ( ) . two other similar books followed, that of metlinger (german) in and of roelans (belgian) in . eucharius roesslin (german) opened the th century of pediatric texts with a text on midwifery and pediatrics, with reviews of the most common ailments of children, including many infections, of course ( ) . the book by leonellus faventinus de victoriis (italian) was published posthumously in and included a chapter on aphthae and another on measles and smallpox. the first english-language pediatric book was published in by thomas phaer, "the boke of chyldren" and included chapters on aposteme of the brayne (meningitis), scalles of the heed, styfnesse of the lymmes, bloodshoten eyes [kawasaki disease?], diseases in the eares, canker in the mouth, quynsye or swelling of throte, coughe, feblenesse of the stomacke and vomiting, fluxe of the belly (diarrhea), wormes, small pockes and measels, fevers, and consumpcion ( , ) . in giovanne p. ingrassias (italian) differentiated scarlet fever (rossalia) from measles ( ) . hieronymus mercurialis (italian) in published a pediatric text that mentioned the king's evil (scrofulous glands) and included chapters on worms ( ) . at the end of the th century, understanding of disease in children had barely advanced beyond the theories and observations of the greeks and romans, restated by the arab physicians, and clinical observation seemed of little value. significant advances, however, were made during the th century. the works of guillaume de baillou (french) published in were important for the first detailed description of whooping cough as a distinct entity, as he described an epidemic in , as well as rubeola and scarlet fever. several important descriptions of diphtheria (morbo strangulatorio, angina puerorum) were made, with its epidemic nature highlighted by johannes sgambatus (italian) in , its pathologic anatomy in by thomas bartholin (danish), who also commented on its contagious nature ( ) , and its method of killing children (paedanchone or child-throttling) by marcus a. severinus (italian) in . the second english language pediatric book, published by robert pemell in , included chapters on lice, scab and itch, ulcers and sores in the head, pain and inflammation of the ears, oral ulcers, feavers, small pox and measels, rheums and cough, flux, worms, inflammation of the naval, and saint anthonie's fire (erysipelas or ergotism) ( , ) . the third english book appeared in , written by j. starsmare and included much the same topics but making the first mention in english of scrofula. franciscus sylvius de le boe (dutch) was a careful clinician and anatomist who published a book on diseases of infants in that included the usual topics. sylvius is remembered best for the aqueduct of sylvius and the sylvian fissure. thomas sydenham, the most respected english physician of the th century, deserves mention here for his careful description of chorea ( ), his very detailed description of measles ( ), and his account of scarlet fever ( ), which surprisingly failed to mention pharyngitis. thomas willis, who described the circle of willis, wrote a careful account of pertussis (chincough) in and said, "the plan of treatment which is usual in other varieties of cough is seldom of any use in this, which is the reason why old women and gypsies are consulted more often than doctors" ( ) . near the end of the th century a small book on diseases of infants was published in london in by walter harris and became very popular, with editions over years. harris also wrote an essay on venereal diseases, a treatise on plague, and in strongly advocated inoculation against smallpox ( ). his comments about summer diarrhea of infants are described below. in summary, the th century was associated with a rebirth of medicine, and for the first time since hippocrates clinical observations became important. anatomists laid a foundation for morbid anatomy/pathology, and there was initial rejection of some of the ancient theories of disease ( ) . in the field of pediatric infectious diseases there was slow progress, but chorea, scarlet fever, scrofula, and pertussis had been recognized clearly as specific diseases. the history of pediatric infectious diseases (but not the medical specialty) in america predates the establishment of the united states. colonial children were afflicted by many epidemic contagious diseases, and a number of very graphic descriptions have been recorded, many referred to in thomas e. cone's history of american pediatrics ( ) . smallpox that affected children was described in on the talbot, a ship en route from gravesend, england, to new england. during the voyage, the reverend higginson wrote an account of his children who became ill with smallpox, including his young daughter who died at sea. epidemics of smallpox, endemic in england through the th century, were described in massachusetts in and again in , when about one-fifth of boston's population succumbed to this scourge ( ) . the first american medical publication, a broadside on smallpox that discussed diagnosis and therapy, was written in by the pastor-physician reverend thomas thacher ( - ) of boston, who practiced part-time pediatrics ( ) . measles was recorded in boston and connecticut in - and again in - , with many children afflicted but apparently relatively few deaths. diphtheria, which was often confused clinically with scarlet fever, was associated with great mortality. the first recorded north american epidemic of diphtheria occurred in in roxbury, ma, with subsequent probable outbreaks documented in in virginia and in new london, ct. scarlet fever, often mistaken for both measles and diphtheria, was first reported in the colonies by shulman both john marshall and cotton mather, who wrote of an epidemic in boston from september to december, . the next epidemic in new england did not occur until . whooping cough caused an extensive epidemic in in young children, but there are no records of subsequent epidemics until ( ) . summer diarrhea in infants was a very serious problem, with very high mortality rates. in england, walter harris ( - ), one of the earliest great "pediatrists" wrote in "from the middle of july to about the middle of september, the epidemical gripes of children are so rife every year, that more of them usually die in one month, than in three or four at any other time. . ." ( ) in the colonies, john josselyn in and john marshall around wrote about children dying of bloody flux (dysentery) and fever ( ) . the pace of progress regarding infectious diseases of children accelerated during the th century, particularly with respect to prevention of smallpox by inoculation or variolation. smallpox was an almost inevitable illness of childhood and was one of the most common causes of death because of its high mortality rate. it was reported, for example, to kill % of swedish children yearly. inoculation with matter from a smallpox subject was introduced into western europe from constantinople around , with limited mortality from the procedure and resulting immunity ( ). other advances were being made as well. richard wiseman (english) , surgeon to king charles ii, wrote extensively about the king's evil (scrofula) and mesenteric adenitis. jean astruc (french) in published an english edition of his lectures on diseases of children that included pertussis, infant diarrhea, worms, purulent lung disease, and scrofula. astruc was among the first to emphasize the importance of a thorough and methodical clinical exam of children. john fothergill (english) in published an important work on ulcerative pharyngitis, with descriptions of diphtheria and scarlet fever ( ). the mid- th century saw the identification of varicella as a disease distinct from smallpox. françois boissier de sauvages (french) in a book on diseases of children described what he thought was a variety of smallpox that he termed "la vérole volante" or the fleeting variola (smallpox). the description is of varicella, which was very clearly distinguished as a separate illness by william heberden the elder (english) in ( ) ( ) ( ) . nils rosen von rosenstein (swedish) published a very important pediatric work in , which was the most progressive and scientific book on pediatrics up to that time ( ). it included a detailed description of a epidemic of scarlet fever, varieties of infant diarrhea (obviously he was a splitter rather than a lumper), and also described varicella but considered it "the chrystalline or watery smallpox" ( ). he described postscarletina dropsy with bloody urine (poststreptococcal nephritis) and had sufficient insight about pertussis to state that "the true cause of this disease must be some heterogeneous matter or seed which has a multiplicative power as is the case with smallpox. . . we find that it is communicated by infection and that a part of it is attracted by the breath down into the lungs." robert whytt (scottish) in published what some consider the finest clinical description of any disease to that time in his "observations on the dropsy in the brain," tuberculous meningitis, in which he detailed the three clinical stages of this disease as well as the autopsy findings ( ) . around this time hugh smith (english) importantly focused public attention upon the staggeringly high mortality rates among children. he showed that from to about two-thirds of children born in london died before the age of five years and that about % of the deaths occurred before two years of age ( , ) . at this time george armstrong founded the first dispensary for children in , which ultimately led to the establishment of children's hospitals. he published a work on the diseases most fatal to infants in , and he wrote in detail about the treatment of the chin-cough (pertussis). michael underwood (english) was probably the most advanced th century writer on the diseases of children ( ) . his treatise, first published in , was reprinted in editions until . he provided the first description of sclerema and poliomyelitis and wrote about coryza maligna, which was either congenital lues or nasal diphtheria. joseph clarke (irish) in described an outbreak of fatal "nine-day fits" among neonates (neonatal tetanus) at the lying-in hospital of dublin. hyacinthus andreas (spanish) had published an account of this condition at the end of the th century ( ). it was in that edward jenner published his report of years of observation and experimentation with the variolae vaccinae, or cowpox, to prevent smallpox. this proved much safer than the procedure of inoculation with smallpox matter (variolation) used earlier in the th century, as described above. at the end of the th century, pediatrics was characterized by increased awareness of the value of children's lives, the beginning of institutions to provide medical care for children and the beginning of instruction of medical students in children's diseases. additional important pediatric infectious diseases had been described, including tuberculous meningitis, varicella, neonatal tetanus, and poststreptococcal nephritis ( ). jenner's studies provided the means to prevent the great morbidity and mortality related to the dreaded smallpox. epidemic diseases were better described during the th century in colonial america compared with the earlier period, and there was clear recognition of the impact of smallpox, diphtheria, scarlet fever, measles, influenza, tuberculosis and whooping cough, particularly upon children. a very severe new england epidemic of diphtheria in - killed more than individuals, mostly children, and was later called "the most horrible epidemic of a children's disease in american history" ( ) . early accounts by jabez fitch ( ) of new hampshire and jonathan dickinson ( ) described these events ( ) . samuel bard ( ) . this work about diphtheria emphasized its infective etiology, "drawn in by the breath of a healthy child," and urged prevention by immediate removal of the young children in the family as soon as a first case appeared in a household. in william douglass ( - of boston provided what is considered the earliest complete description of scarlet fever, terming it angina ulcusculosa ( ) . in , dr. benjamin rush ( - ) described a widespread epidemic of scarlet fever ("scarlatina anginosa") occurring in philadelphia in and , while pertussis was described in detail in by lionel chalmers ( chalmers ( - in an account of the weather and diseases of south carolina ( ) . dysentery ("bloody flux") was emphasized as a serious and very common problem of children particularly in summer when benjamin rush wrote in detail about "cholera infantum" (and coined the term) in ( ) . rush was the most influential american physician of his day and a signer of the declaration of independence, and he lectured and published regarding pediatric disorders, including cholera infantum and diphtheria ( ) . cholera infantum, or summer diarrhea, appeared each year in epidemic form and emerged later as a particularly important problem for young children, as more crowded urban areas developed. in rush also described a major epidemic of yellow fever in philadelphia which killed about one-eighth of the population ( ) . particularly severe epidemics of measles were noted in , , , , and . more than children in charleston, sc died in the epidemic alone ( ) . cotton mather's diary in recorded the death of his wife, the maid, his neonatal twins, and another child in his family within a -d period ( ) . this serves as a striking reminder about this now-preventable illness. other primarily pediatric illnesses including thrush, mumps, tinea capitis, and worm infestations also were clearly described in the colonies of the th century ( ) . in contrast to europe, where smallpox was an endemic illness of childhood, in the colonies smallpox occurred in large epidemics with about -year periodicity and affected children as well as older susceptible individuals. this became an important issue during the revolutionary war, when the troops of the continental army (but not the british forces) were ravaged by smallpox until general george washington at valley forge decided to inoculate all susceptible troops. this act probably saved the war effort ( ) . from to about , the major causes of death in children were tuberculosis, diarrhea of infancy, bacillary dysentery, typhoid fever, and the highly contagious diseases of childhood, especially scarlet fever, diphtheria, and lobar pneumonia ( ). significant fluctuations occurred. for example, for the first three decades of the th century, the severity of scarlet fever was less than observed previously but then around increased dramatically. by scarlet fever had become the leading cause of death among the infectious diseases of childhood in the u.s., great britain, and europe ( ) . changes in the virulence of prevalent group a streptococcal strains would seem most likely responsible for such fluctuations, as seen in new york city, for example, where only scarlet fever deaths were recorded from - , but deaths by ( ) . reports about other pediatric infections also exist. in nathan smith of lebanon, nh, founder of dartmouth medical school, successfully treated joseph smith ( - ), an unrelated -year-old boy, for osteomyelitis, removing bone from the left lower leg but avoiding amputation. long-term drainage apparently occurred with discharge of additional pieces of bone, and crutches were used by the child for more than three years. joseph smith, who retained a slight limp, later founded the mormon church ( ) . for a period of about years, from - , eli ives, the first u.s. medical school faculty appointee in pediatrics, lectured yale medical students on the diseases of children. the surviving lecture notes show that these lectures included a number of infectious diseases topics as they impacted children ( ) . also in the first half of the th century, william potts dewees ( ), george logan ( ), and john eberle ( ) each published very early pediatric texts, each of which included sections on the infectious illnesses of children. dewees of philadelphia was an adjunct professor of midwifery, and his text, the first truly comprehensive american pediatrics book, has more than pages devoted to infections, including not only epidemic illnesses but also abscesses of the hip joint and ear, worms, and whitlow (paronychia) ( ) . epidemic spotted fever, or cerebrospinal meningitis, was described in detail by elisha north ( - ), who reported the connecticut outbreak of meningococcal infection ( ) . in william wood gerhard ( - ) provided the first american description of tuberculous meningitis (actually describing children he saw in paris), and in and he distinguished typhus from typhoid in children at the pennsylvania hospital. gerhard also in was perhaps the first to record percussion and auscultation findings in pediatric pulmonary diseases ( ) . his parisian training clearly exposed him to laennec's critically important invention, the stethoscope ( ). very substantial advances were made in european pediatrics, particularly with respect to infectious diseases, throughout the th century. john cheyne (scottish, irish) published a number of important works, including "the pathology of the membranes of the larynx and bronchia" in , a description of the - dublin fever epidemic, and three studies of cynanche trachealis (croup), and described cheyne-stokes respirations ( ). pierre bretonneau (french) described the contagious nature of typhoid fever ( - ) and of diphtheria ( ). he performed the first successful tracheostomy for diphtheria on july , , on a child, elizabeth de puységur ( ). in he distinguished typhoid from typhus clinically. the most important pediatric text of the early th century was by charles-michel billard (french). this work built upon that of bichat and laennec, who provided the initial scientific basis of shulman medicine, and classified pediatric disorders (including infectious diseases) based not upon symptoms but upon pathologic lesions, i.e. upon autopsy findings ( ) . armand trousseau (french) performed the first tracheostomy in paris ( ), described laryngeal tuberculosis, cutaneous and mucosal diphtheria, pediatric cholera, and he originated the technique of thoracentesis in pleurisy. frédéric rilliet (swiss) wrote on typhoid in children ( ), epidemic measles ( ), mumps ( ), and cholera ( ). his text ( - ) with antoine-charles-ernest barthez (french) included classic descriptions of tuberculosis of the bronchial glands, bronchopneumonia, and chronic pleurisy. charles west (british) ( - ) was considered the greatest english "pediatrist" of the second half of the th century. in he established the children's hospital in great ormand street, london. his pediatric text of , which went through seven editions and numerous translations, included outstanding descriptions of infantile tuberculosis and poliomyelitis and emphasized the importance of breast feeding in the prevention of infantile diarrhea. johann rehn (german) studied epidemic jaundice (infectious hepatitis) in children ( ), while his countryman eduard heinrich henoch, a pupil of schönlein, described abdominal purpura (henoch-schönlein purpura) in . nil f. filatoff (or filatow) (russian) published a series of lectures on the infectious diseases of children ( - ), in which he described "scarlatinal rubella" termed "fourth disease" or filatoff-dukes disease ( ). marie-jules parrot (french) described the pseudoparalysis of congenital syphilis ( ) that still bears his name ( ) . jacques-joseph grancher (french) wrote extensively on tuberculosis ( - ) and pioneered isolation and antisepsis (infection control) at the hôpital des enfants malades, paris ( - ), housing infectious patients in wire cages and using surgical gowns for staff ( ) . bernard-jean-antonin marfan (french) wrote important works on pediatric typhoid ( ), peritonitis ( ), congenital infections ( ), infantile gastroenteritis ( ) and diphtheria ( ) . friedrich bezold (german) in provided the first clear description of mastoiditis ( ) . henry ashby (british) was a pediatrician and public health officer who led the movement in britain to advocate for a pure milk supply during the s and early s. sir arthur newsholme (british) in the late th century and early th century provided extremely important data related to changes in infant, child, and maternal mortality primarily due to infectious diseases, particularly rheumatic fever ( ), epidemic diphtheria ( ) , and tuberculosis ( ) ( ). before , there was no organized group of physicians for children in the u.s. and, of course, no specific subspecialty fields within health care for children. the section of diseases of children of the american medical association was organized in at a meeting of the ama in richmond, va, with abraham jacobi chosen as president and thomas morgan rotch as secretary ( , ( , ) . he was the first to teach medicine at the bedside ( ). jacobi is often called the "father of american pediatrics" and wrote extensively on a variety of pediatric problems, with his most frequent subjects related to infectious diseases, notably diphtheria. he advocated the use of boiled milk for infants (for nutritional reasons as well as to prevent the gastroenteritides). the inaugural issue of the ama's american journal of obstetrics and diseases of women and children in , the first partially pediatric journal in the u.s., included an article on croup by jacobi. jacobi was an ardent social and political activist, striving to improve the circumstances of children. because the ama group began to flounder and the membership of the obstetrics and gynecology sections refused to allow pediatrics to form a separate section, a new group, the american pediatric society, the parent of organized pediatrics in the u.s., held an organizational meeting on september - , , at the arlington hotel in washington d.c., with physicians present ( , ) . credit for forming the group is given to job lewis smith ( - ) of bellevue medical school and william booker ( - ) of baltimore, the first clinical professor of the diseases of children at johns hopkins. jacobi was elected the first president, and there were founding members, predominantly from the northeast, including william osler, who later served as the fourth aps president ( ) . four papers were scheduled to be presented (although it is not clear from the minutes that any of them in fact was presented), including "treatment of whooping cough by antipyrin" by l. emmett holt, sr., of new york ( ) . holt was professor of pediatrics at the new york polyclinic hospital and attending physician at babies hospital in new york. he was a founder of the american pediatric society and served as president in and then again in . holt's presidential address in recapped his personal experiences with new york city children's hospitals, pointing out the discouraging % mortality for hospitalized infants and the very frequent nosocomial infections that occurred. he advocated care in the country, away from the crowded cities, during the summer months ( ) . this theme was echoed by henry koplik of new york, aps president in , who reported the continued problem of summer diarrhea and recommended ambulatory care and a "colony or camping system" with care provided by live-in mothers ( ) . although it had improved somewhat compared with colonial times, the plight of children at the time of the founding of the american pediatric society in continued to be hazardous. coincident with the industrial revolution, mortality rates had climbed substantially from early in the th century to the later years of the th century as major crowded urban areas developed. life expectancy around was less than years, infant mortality approached per births, and neonatal mortality was about per births ( , , ) . the infant mortality rate in in new york city, a particularly crowded urban area, was history of pediatric infectious diseases as high as per live-born infants, primarily related to various infectious processes. infectious diseases such as diarrhea, diphtheria, scarlet fever and tuberculosis dominated as the major causes of morbidity and mortality among children, and they had yet to be impacted by the just-emerging scientific base of medicine. the science of bacteriology, founded on the landmark discoveries of louis pasteur in paris, robert koch in berlin, and others in the early s, had not yet impacted child health. roentgen had not yet discovered x-rays. biochemical analyses were not available for infants and children. inadequate sanitation, impure water and unsafe milk supplies all contributed very significantly to the spread of infectious diseases among infants and children, and particularly to those living in the very crowded circumstances that promote transmission. the early years of organized u.s. pediatrics were marked by a number of landmark advances in the diagnosis and treatment of infectious diseases of children, with substantial reduction in infant mortality rates, to / live births in new york city in , with rates as low as in chicago and as high as in biddeford, me ( ). the importance of infectious diseases to the relatively small number of founding members of the american pediatric society, a group of distinguished physicians who devoted much or all of their effort to the improvement of the health of children, is reflected by analysis of the topics of the papers presented at the early annual scientific meetings of aps. the first scientific meeting of the aps held in washington on september , , and the next day in the then-new johns hopkins hospital included many presentations devoted to classic infectious diseases. these included two papers devoted to diphtheria, two elaborate bacteriologic studies of the stools in infant diarrhea (booker isolated bacterial varieties and jeffries different organisms), a paper on malaria in new york city, two papers related to infant feeding and prevention of infant diarrhea, and assorted case reports ( , ) . at least of the papers delivered at the first five annual scientific meetings ( - ) directly addressed infectious diseases topics, including diphtheria ( ), diarrhea ( ), scarlet fever and rheumatic fever ( ), tuberculosis ( ), pneumonia and empyema ( ), typhoid fever ( ), pertussis ( ), lues ( ), vulvo-vaginitis ( ), malaria ( ), and miscellaneous infections ( ) ( ). this dominance of the scientific agenda by infectious diseases topics attests to their extreme importance as the major causes of morbidity and mortality in childhood at the end of the th century. hippocrates had recognized the unfavorable implications of a sort of spiderweb (or membrane) in patients with tonsillar ulcers ( ) , and both bard's contribution and the introduction of tracheostomy for laryngeal diphtheria in france in the s have been noted (vide supra). diphtheria was of particular concern at the early american pediatric society meetings, as the laryngeal form of the disease in that era was almost invariably fatal, despite the use of tracheostomy. the few years just before the founding of the aps and the early years of the organization represented a period of landmark advances in understanding the etiology of this illness and in the development of markedly improved treatment modalities. in friedrich loeffler proved that a specific bacterium was the etiologic agent of diphtheria. the introduction of the o'dwyer intubation tube in received great attention because for the first time it enabled successful treatment of the suffocation that was associated with laryngeal diphtheria ( ) . joseph o'dwyer ( - ), attending physician at the new york foundling hospital, a facility for unwanted children, was a founder of american pediatric society, and he served as president of aps in ( ) . o'dwyer's presidential address reviewed his invention and experience with the intubation tube ( , ) . at the th annual scientific meeting of the aps in , papers from four groups regarding the dramatic, even revolutionary, effects of diphtheria antitoxin for therapy and prevention were presented. this led to the adoption of a formal resolution: "resolved, that, in the opinion of the society, the evidence thus far produced regarding the effects of diphtheria antitoxin, justifies its further and extensive trial" ( , ) . a committee was apparently appointed, as the annual meeting included a report from the american pediatric society's collective investigation of the antitoxin treatment of diphtheria in private practice, chaired by l. emmett holt. this confirmed the spectacular results of the french report by roux, martin, and chaillou from the pasteur institute in paris. the meeting received a report from the committee on collective investigation of the antitoxin treatment of laryngeal diphtheria in private practice, chaired by william p. northrup ( ) . these clinical studies of diphtheria equine antitoxin represented the first pediatric investigations in the u.s. of a national scope. the four committee members analyzed cases of laryngeal diphtheria treated with antitoxin who were submitted by aps members and concluded that antitoxin lowered the necessity for intubation from % to % and the mortality rate from % to % in this severest form of diphtheria ( ) . the schick test to assess susceptibility to diphtheria was introduced by bela schick in . emil von behring of germany, who initially discovered diphtheria toxin and developed the diphtheria antitoxin that was of such great interest and importance, was awarded the first nobel prize in medicine in for this work. tuberculosis and meningitis. tuberculosis was another very common and serious problem of childhood, and william osler was very actively involved in its study before moving to oxford, england, in to become the regius professor. osler's commitment to pediatrics is apparent from his frequent participation in the aps meetings to discuss tuberculosis, pertussis, chorea and carditis, croup, peritonitis and other topics, as well as from the % of his writings which are on pediatric subjects. he was particularly interested in tuberculosis of childhood and presented a paper at the third aps meeting in on pulmonary tuberculosis in children, in which he divided it into acute, subacute, and chronic or protracted forms ( , ) , and another in that included autopsy findings ( ) . papers on childhood tuberculosis were presented at virtually all of the aps scientific meetings during the early decades. shulman particularly noteworthy milestones included walter carr's presidential address that reported a % decline in extrapulmonary tuberculosis, the report by the parisian armand-de lille of the diagnostic value of gastric aspirates in infants, the report by bela schick and colleagues on the bcg vaccination introduced three years earlier in france, detroit's joseph johnston's discussion in of the evolution of pediatric tb to the adult type by endogenous reactivation, and the exciting initial report in by john lyttle and colleagues from los angeles of the recovery of a patient with miliary tb after streptomycin treatment ( ) . meningitis, including the invariably fatal tuberculous meningitis, was also a common affliction of children in the late th century. abraham jacobi wrote about meningitis that the u.s. "more than any other country has been invaded by this plague" ( ) . at the meeting of aps, august caillé ( - ) presented a paper on "tapping the vertebral canal in the lumbar region" and the following year a paper on "local treatment for tubercular meningitis" ( ). these were the first reports to the aps of diagnostic lumbar puncture, after it had been introduced by quincke in as a treatment modality ( , ) . two additional papers presented in discussed lumbar puncture in the subarachnoid space, which provided a scientific basis for studying meningitis, with measurement of sugar and protein, and a potential route of administering therapy, such as it was in the late th and early th centuries ( ). summer diarrhea and the milk supply. in addition to the introduction of intubation techniques and diphtheria antitoxin, an exceptionally important advance during the late th century and early th century was the result of efforts by concerned pediatricians and others to secure a safe and sanitary milk supply for infants ( ) . nonbreast-fed infants experienced particularly high mortality rates, because much of the cow milk supply was "swill milk," which came from cows fed only distiller's mash, housed in incredibly filthy conditions, without fresh air, exercise or hay, many of which were also infected by bovine tuberculosis ( , , , ) . job lewis smith, who was one of the first to differentiate rubella from rubeola and wrote several papers on neonatal tetanus, served as the second aps president in , years after he had written in his textbook that more than half of new york's infants who were spoon-fed (i.e. not nursed or wetnursed) in the summer, died before fall ( ) . he strongly urged milk sterilization and wrote and spoke about the dangers of artificial infant feeding. bacteriologic studies of milk began to establish a scientific basis for the association of impure milk with infant diarrheal illnesses, including the work of the pediatrician escherich in , shiga in , and flexner in . the genera escherichia and shigella (as well as the species shigella flexneri) honor these pioneer bacteriologists. william d. booker's major area of interest was summer diarrhea of infancy. he presented a paper at the first aps scientific meeting in on that topic ( ), and he devoted his presidential address in to the early history of summer diarrhea in america from colonial times ( ) . the problem of summer diarrhea and its increasingly clear relationship to contaminated milk in the urban poor was highlighted by the report of infant deaths per week in new york city during the hot weather summer months that were associated particularly with bottle feeding ( ) . considerable attention of organized pediatrics was focused on this issue, particularly by henry l. coit ( - ) , smith, rotch, isaac abt, schick, and others, who advocated movement toward certified safe milk ( , ) . coit began as early as to work tirelessly to ensure a safe milk supply for infants, after the death of his young son, by educating the public, lawmakers, and the medical community ( ) . he coined the term "certified milk" and established the first medical milk commission in new jersey ( ). henry koplik (president of aps in ) established the first american clean milk depot in new york in (called gouttes de lait), and thomas morgan rotch (a founder of aps and president in ) organized the walker-gordon farms that led to the first milk laboratory for preparing safe milk formulas. pasteurization of milk by heating was introduced in europe before (and had been used for wine since !), and it was promoted particularly by jacobi in the u.s. during the s for its ability to prevent milk-borne infections. many other academics preferred certification as an alternative to pasteurization, fearing that the latter would alter the chemical composition of milk and promote gastroenteritis. this proved wrong ( ) . jacobi collaborated with the philanthropist nathan straus to establish pasteurization plants and milk stations for poor infants in new york beginning in . a reduction in infant mortality of % was observed in just one year in the foundling hospital on randall's island after a pasteurization plant was established there by straus ( , ). however, it was not until that chicago became the first city in the world to require pasteurization of milk, with many cities following thereafter ( ) . controversy in this area was apparent early on, best exemplified perhaps by the resignation from the aps in of arthur v. meigs of philadelphia, who argued vehemently against milk sterilization and who continued to reject the germ theory of disease until his death in ( , ) . thomas m. rotch ( - ) was america's first full professor of pediatrics, appointed at harvard in . rotch published a major textbook of pediatrics in as well as early reports of the value of the roentgen ray in pediatrics, in addition to his detailed studies of milk. although extremely focused on the biochemical composition of milk, calculating in minute detail the precise amounts of protein, fat and sugar content of milk for infants, he also recognized the importance of a safe milk supply and worked to achieve that goal. the improved milk supply was complemented by studies, primarily at johns hopkins, by holt, james gamble, w. mckim marriott, john howland, and others, that led to understanding the roles of acidosis and dehydration in contributing to the mortality of infants and children with acute diarrhea. this led directly to effective rehydration and correction of electrolyte imbalances in such children with improved outcomes ( ) . scarlet fever. in the latter decades of the th century, case-fatality rates for scarlet fever were very high, particularly in the youngest children. holt's textbook, the diseases of infancy and childhood, indicated the case-fatality rate to be as high as % in those under one year and % to % in those under three years ( ) . wide year-year fluctuations were some- history of pediatric infectious diseases times observed, with annual death rates during the decade of the 's, for example, from as low as / , to a high of / , population. representative case-fatality rates during the latter years of the th century were . % in new york in , % in - in providence, ri, and . % in philadelphia in ( . % for those - years old) ( ) . in addition to person-person spread of streptococcal infections including scarlet fever, contaminated milk was also shown to produce explosive epidemics of very acute streptococcal pharyngitis with high mortality. this provided an additional reason to support pasteurization of milk ( ) . by the close of the th century, scarlet fever had overtaken diphtheria as a cause of death, occurring with great frequency and often with high case-fatality rates. the pediatric text of louis starr ( - ) described scarlet fever as the most widely disseminated of the childhood exanthems and "the most dreaded of all the diseases of children." ( ) poliomyelitis. poliomyelitis, which was initially described in underwood's first edition in , was brought to general medical attention by jacob von heine (german). von heine was a pioneer of orthopedics who published a classic monograph on infantile paralysis and its resultant deformities in , and he recognized the spinal cord localization of the pathology ( ). the classic french pediatric text of rilliet and barthez ( - ) provided an early account of polio, and guillaume-benjamin-amand duchenne (french) localized the lesion in polio to the anterior horn cells in ( ) . later in the th century, oscar medin (swedish) first noted the epidemic character of polio when he observed an outbreak of cases in stockholm in ( ) . in a larger epidemic of cases occurred in rutland county, vt ( ). from the turn of the century until about , the pediatric community focused particularly upon major public health and welfare issues that adversely affected children, working particularly hard to improve the milk supply. walter l. carr's presidential address to the aps very clearly spelled out the impressive improvements in the health of children that had occurred during the early years of the th century ( ) . infant mortality in greater new york city declined % from / live births in to in . as a consequence of the efforts to improve the milk supply, diarrheal deaths had declined %. mortality from measles, scarlet fever, pertussis, and diphtheria had declined %, while that from acute respiratory disease including pneumonia fell % ( ) . during the period from to , the etiologic agents of more than infectious diseases were identified ( ) . as microbiologic advances were made, american pediatric society meetings continued to include many papers related to epidemic infectious diseases including summer diarrhea, poliomyelitis, typhoid fever, gonococcal infection, and meningococcal meningitis. increasingly large u.s. poliomyelitis epidemics occurred, primarily affecting children, for example in new york city in , with almost cases and up to % mortality ( ) . this peaked in a epidemic in the northeast with almost , cases and , deaths, many in the new york city area, leading to massive public anxiety and aggres-sive public health measures including quarantine and travel restrictions ( ) . progress in understanding the etiology and pathogenesis of polio was made early in the th century. in vienna in landsteiner and popper transmitted polio to monkeys by intraperitoneal injection of spinal cord material from a child who died early in the course of polio. also in simon flexner (of shigella flexneri fame) and paul lewis in new york extended those studies to show transmission to monkeys also after s.c., i.v., or intracerebral routes of inoculation and produced disease using filtrates of nasopharyngeal washes from polio patients ( ) . additional flexner studies from - showed that sera from monkeys that recovered neutralized the infectivity of polio material, that intrathecal injection of convalescent sera within h of inoculation prevented paralysis, that recovered monkeys were protected against subsequent inoculation, and that recovered human patient sera contained antibodies to the infectious agent ( ) . great effort was devoted by several groups to use intrathecal administration of convalescent polio sera to treat children with acute poliomyelitis but this proved unhelpful ( ) . the development of the iron lung by philip drinker in the late s was a noteworthy therapeutic advance for affected patients. during the period from to , the application of serum therapy to the management of diphtheria, meningococcal and streptococcal infections served as topics for many aps presentations ( ). jacobi's second aps presidential address, in , was entitled "the tonsil as a portal for microbic and toxic invasion," while that of j. l. morse in reviewed the high mortality of pertussis, especially in infants, and proposed stringent isolation ( ) . specific therapy for congenital syphilis with salvarsan, introduced by ehrlich two years earlier, was reported by lafétra in , with dramatic benefit ( ) . in his aps presidential address in , l. emmett holt summarized the dramatic improvement in mortality in those less than five years old from infectious diseases in manhattan and the bronx from - to - , with approximately an % decline in diarrheal deaths, diphtheria and croup, and % for pneumonia ( ) . over the next decades (~ - ), academic pediatricians and their research were focused particularly upon nutrition and the biochemistry of health and disease, which during this time somewhat eclipsed infectious disease concerns ( ) . nevertheless, syphilis, tuberculosis, pertussis, measles, rheumatic fever, streptococcal infections, polio, and meningitis continued to interest those caring for children, as reflected by papers presented at the annual aps meetings. active immunization against diphtheria using toxin and antitoxin was introduced by alfred hess in the u.s. in ( ) . at the end of this era, a particularly interesting paper was presented in by francis schwentker, who reported the treatment of meningococcal meningitis with s.c. and intrathecal para-aminobenzenesulfonamide (sulfanilamide) ( ) . the first use of an antimicrobial agent in the u.s. was by future aps president a. ashley weech, whose unsuccessful treatment of a physician's child with h. influenzae meningitis with the sulfanilamidecontaining compound sulfachrysoidine in has been well documented ( , ) . the actual administration of this agent was by the chief resident at babies hospital in new york, f. shulman howell wright, who later served as chair of pediatrics at the university of chicago and president and executive secretary of the american board of pediatrics ( ) . during this era, several aps presidential addresses concerned infectious disease issues, including that by linnaeus lafétra in regarding the need for preventive measures against infectious diseases and rheumatic fever in children two to six years old; by thomas s. southworth in on the communicability of acute pneumonia and the need for isolation of such patients, as was done for tuberculosis patients; by l. emmett holt in highlighting the decline in infectious diseases, particularly diarrhea, diphtheria and acute respiratory disease (as discussed above); and by henry f. helmholtz in on infections of the renal parenchyma and the importance of stasis in predisposing to urinary tract infection ( , ) . during this period the first pediatric department with several identified subspecialists was developed by edwards a. park at johns hopkins beginning in . under the previous leadership of john howland from - , there had not been any special clinics or pediatric subdepartments at hopkins, with the exception of a clinic for the treatment of congenital syphilis. curiously it was lawson wilkins, later known as the father of pediatric endocrinology, who initiated and organized the congenital syphilis clinic as an intern ( ) . as a discipline, infectious diseases did not figure as prominently as cardiology, endocrinology, neurology and other nascent subspecialty areas under park's leadership. this theme was replicated in most other academic departments as subspecialization began to develop. a few exceptions were pediatricians known for their expertise in contagious diseases, some of whom were particularly interested in vaccine development. these included bela schick at mt. sinai and at albert einstein in new york, hattie alexander and horace hodes at columbia university, joseph stokes at university of pennsylvania, russell blattner at baylor, william bradford at rochester, amos christie at vanderbilt, katherine dodd at vanderbilt and cincinnati, edith lincoln at new york university, louis sauer at evanston, il, and john zahorsky in st. louis. by , when the american pediatric society was a halfcentury old, life expectancy had increased to over years, infant mortality had declined to about / and neonatal mortality to about / ( ) . sewage and sanitation had improved greatly, which along with much safer milk supplies had led to a marked fall in diarrheal illnesses of infancy. a few vaccines had been introduced, but antibiotic therapy was limited to the early use of sulfanilamide. at the th annual meeting of aps in , the first held in conjunction with the young society for pediatric research (spr), important papers presented included that of trask and paul, reporting the isolation of poliovirus from nasal washes and stools of asymptomatic patients, several related to the pathogenesis of pertussis, that of lyttle showing elevated aso titers in acute glomerulonephritis, hodes' report of an irradiated rabies vaccine, and stokes' isolation of various strains of influenza virus. these works served as the prelude to the much more dramatic advances to come, related to the pathogenesis, diagnosis, and treatment of viral and bacterial infections of children ( ). between and , three new pediatric organizations emerged: the american academy of pediatrics in , the society for pediatric research in , and the american board of pediatrics in . the eastern society for pediatric research, organized in , became a national organization (also including mexico and canada) called the society for pediatric research (spr) in , with the goals to foster research in pediatrics and to serve the younger pediatric faculty (Ͻ years old), as the aps meetings were quite closed to junior investigators. the first meeting of the spr was held in may, , and since the aps and spr have held joint meetings, with greater prominence of infectious diseases as a separate subspecialty in more recent years. presidents of spr who have been associated with a particular interest in infectious diseases are shown in table . the american academy of pediatrics (aap) was founded in to promote the welfare of children. this occurred after the american medical association house of delegates severely chastised the pediatric section of the ama for taking pro-active stances favoring the sheppard-towner act, which supported maternal and child health. isaac abt of chicago became the first president of the aap, which had charter members and held its first meeting in atlantic city, nj, on june - , ( ) . early in its existence, the aap declared its interest and involvement in infectious diseases issues. the aap established a special committee on prophylactic procedures against communicable diseases in , chaired by edward b. shaw of san francisco and including j.e. gordon of detroit and j.a. toomey of cleveland. this committee was disbanded after its report "routine measures for the prophylaxis of communicable diseases" was published in the journal of pediatrics in april ( ) . this six-page report dealt with diphtheria, scarlet fever, typhoid fever, whooping cough, measles, smallpox, polio ( lines), epidemic meningitis ( line), mumps and chickenpox ( lines), rabies, and tetanus. the committee on immunization procedures was then established in , with john a. toomey as chair. three years later the committee name was changed again to the committee on immunizations and therapeutic procedures for acute infectious diseases, in it was modified again to the committee on control of infectious diseases, and then in to the committee on infectious diseases, the current name, although it is now most commonly referred to as the red book committee. since , this aap committee has published a report every one to five years (every three years for the past five editions), which because of the color of its binding has been known as the red book for many editions. after world war ii came the postwar boom, noteworthy for the expanded availability of federal research funds (especially from the national institutes of health), increasingly sophisticated research and technology, the development of vaccines against polio and measles, and the discovery of ever-moreactive antibiotics and other anti-infectives, with the initial emergence of antibiotic resistance, e.g. penicillin-resistant s. aureus. the period from to about heralded the era of modern infectious diseases and coincided with the increasing trend to subspecialization within pediatrics and the development of full-time pediatric departments. antimicrobial advances included the discoveries of streptomycin, isoniazid and then other agents to treat tuberculosis, as well as penicillin, chloramphenicol, streptomycin and other antibiotics for treatment of bacterial infections. virtually universally fatal infections such as bacterial meningitis and endocarditis became amenable to therapy. american pediatric society presidential addresses during this period that dealt with infectious diseases topics included that by jean v. cooke in discussing the impact of specific therapy including antimicrobials upon the common contagious diseases and reviewing mortality statistics ( ). this era was associated with the virtual elimination of congenital syphilis, early studies of bacterial resistance to antibiotics, improved methods of viral cultivation, but also large poliomyelitis epidemics. the control of acute rheumatic fever and rheumatic heart disease was a consequence of the studies of floyd denny, lewis wanamaker, and others that proved that recurrent attacks could be prevented by antibiotic prophylaxis. edith in the period from to about has been termed the era of specialization and fragmentation of pediatrics by howard pearson ( ) . at the onset of this era, the program of the society for pediatric research listed no infectious diseases subspecialty session per se but rather one session devoted to "microbiology/immunology" that included a handful of papers (out of the in total that were presented) on topics that can be considered infectious diseases issues. several aps presidents during this era were closely linked to the emerging field of pediatric infectious diseases. (see table ). warren wheeler in in his presidential address dis- shulman cussed the epidemics of enteropathogenic e. coli in the s and s and those of s. aureus / in the s, recommending surveillance to detect emergent bacterial "hot strains" ( ) . saul krugman, aps president in , devoted his distinguished career to the field of infectious diseases, especially to the study of hepatitis viruses. fred robbins ( ) and horace hodes ( ) were each responsible for signal discoveries in virology, the former having received the nobel prize in with john enders and tom weller for the development of tissue culture technology that led to viral vaccine production, and the latter devoting his life to investigations of viral gastroenteritis of infants and vaccine development ( ) . margaret h. d. smith ( ) worked tirelessly in the field of pediatric tuberculosis and advocated for social activism by organized pediatrics. c. henry kempe ( ) was instrumental in the eradication of smallpox, and floyd denny ( ) contributed to the understanding of group a streptococci and to the conquest of rheumatic fever. during this era, infections in the immunocompromised child began to emerge as an important clinical problem, as increasing numbers of cancer patients and other compromised patient populations were generated by improved treatment modalities ( ) , and these were accompanied by increasing numbers of opportunistic viral, fungal and bacterial infections requiring expert management. it was during this time that many subspecialty organizations within pediatrics were born, including the pediatric infectious diseases club. formal organizations within the field of pediatric infectious diseases emerged gradually as the subspecialty became more clearly defined and differentiated from the rest of pediatrics during the s and s. in - plotkin of philadelphia led the establishment of the pediatric infectious diseases club, which held its first election of officers in - . this club evolved into the pediatric infectious diseases society (pids) in , and it has grown into a very active organization to which the vast majority of those in the field belong. the modern era, from about to the present, is the period of modern molecular biology and genomics, with advances based upon new diagnostic modalities such as dna hybridization and sequencing, cloning, pcr, magnetic resonance imaging, pet scanning and many others. laboratory techniques for research related to pediatric illnesses have used these and other increasingly sophisticated molecular methods. the elucidation of the first bacterial genome, that of hemophilus influenzae, in heralded vast new opportunities to understand the pathogenesis of infectious diseases ( ) . although many classic pediatric infectious disease disorders have virtually disappeared, new (or apparently new) clinical challenges such as opportunistic infections in the ever-increasing populations of immunocompromised patients, lyme disease, kawasaki disease, sars and hiv/aids have emerged. the onset of the aids epidemic in the early s and the identification of hiv as its causative agent had a substantial impact upon the specialty of pediatric infectious diseases. identifying perinatal vertical transmission risk factors, dealing with transfusion-associated hiv infection (particularly in the hemophiliac population), and determining the clinical, virologic and immunologic parameters of pediatric aids occupied the first decade or so of the pediatric aids experience. the landmark report of the pediatric aids clinical trials group protocol that demonstrated the marked effectiveness of zidovudine administered to pregnant women to prevent vertical transmission of hiv led to dramatic reduction in the number of perinatally infected children within several years in developed countries. in other areas of the world, where antiretroviral therapy during pregnancy is not being utilized, vertical transmission of hiv continues unabated. in recent years, in the u.s., the field of pediatric aids has focused increas- ingly upon prevention and treatment of adolescent hiv infection as well as upon the highly effective multi-drug therapies. table provides a listing of presidents of aps with major interests in infectious diseases issues. recent aps presidents have included sam katz ( ), whose career has been devoted to vaccine development and implementation; paul quie ( ), a bacterial phagocytosis scholar; vince fulginiti ( ) , who advanced the fields of prenatal infections and viral vaccinology; and ralph feigin ( ), an authority on meningitis and many other aspects of pediatric infectious diseases. the american board of pediatrics (abp), which was founded in , first certified general pediatricians in . it then provided its first subspecialty certification in (cardiology). in may the abp approved a proposal from the pediatric infectious diseases society to certify individuals in pediatric infectious diseases, and the abp then applied to the american board of medical specialties (abms). abms approved this application on march , , and the abp established the sub-board of pediatric infectious diseases in ( ) . the initial certifying examination in pediatric infectious diseases was offered on november , with candidates taking the examination and passing ( ) . by , after program applications were submitted and reviewed, a number of training programs for pediatric infectious diseases fellows were accredited by the accreditation council for graduate medical education (acgme). several publications have been developed within the field of pediatric infectious diseases, sponsored by various organizations. the aap's report of the committee on infectious diseases (the red book) is mentioned above. the pediatric infectious diseases society organized the establishment of the report on pediatric infectious diseases, published by churchill-livingstone ten times yearly, beginning in january . in the report was changed to concise reviews of pediatric infectious diseases and was incorporated within the monthly pediatric infectious diseases journal. the latter journal had been the discipline of pediatric infectious diseases has a great many remaining challenges. these include the conquest of illnesses that affect children in the developing world, most notably hiv infection, tuberculosis and falciparum malaria, but also a wide array of other infections. opportunistic infectious diseases that affect immunocompromised children will also continue to demand attention, and this host population will likely increase. medicine has entered the genomic era, and the quantity of genomic data available, both microbial and mammalian, is increasing at a phenomenal pace. this has had, and will continue to have, profound implications for the study and practice of pediatric infectious diseases. since the elucidation of the h. influenzae genome with . million base pairs in ( ) , almost bacterial genomes have become available, including that of group a streptococcus ( ) and other important human pathogens. the group a streptococcal genome work was led by joseph ferretti, who trained at the university of minnesota with elia ayoub and lewis wannamaker. additionally, the human genome project published drafts of the dna sequence of homo sapiens in ( , ) . these developments unlock the potential for significant advances with impact on all aspects of the field of pediatric infectious diseases. pathogenesis of infections, new insights into the host-parasite relationship, mechanisms of host susceptibility and resistance, resistance to current and development of new anti-infective therapies, new vaccines, and the identification of new drug targets are some of the areas that will be impacted directly. utilization of dna microarray analysis as well as new methodologies of proteonomics will facilitate new insights into the characterization of gene expression during health as well as in disease states, with identification of new antimicrobial targets and identification of infectious disease risk factors for individuals. additionally, the field of pediatric infectious diseases will be impacted for the foreseeable future by issues related to the threat of bioterrorism and the public health response to this threat. this includes the renewal of smallpox immunization in the u.s. as well as focus upon prevention and treatment of anthrax and other potential bioterrorism threats. the unex-pected appearance of new infectious diseases (e.g. severe acute respiratory syndrome -sars) highlights the potential for previously unknown agents to emerge as major threats, and the discipline must learn whether they can cause congenital infection, transfusion-associated infection, and if they particularly target vulnerable populations such as children. pediatric infectious disease physicians can rightfully celebrate the past triumphs of their discipline and should anticipate future outstanding achievements, all of which contribute directly and indirectly to improved health for children. post-script. this history of the development of the field of pediatric infectious diseases in the united states has been written so that it does not overlap the contribution of baker and katz entitled "childhood vaccine development in the united states" ( ) . therefore, it includes little if any information related to the highly successful development and implementation of vaccines for children that have been so instrumental in improving the health of children. rather, this history is focused upon infectious diseases of children per se and upon the development of the subspecialty. viral infections and vaccines hodes-viral vaccines viral infections robbins-viral vaccines rheumatic fever/streptococci steve kohl-herpes viruses hostetter-candidal infections fleisher-bacterial infections job lewis smith-diarrheal illnesses william osler-tuberculosis, etc walter carr-epidemic diseases other infections freeman-infectious diseases churchill-bacterial infections linnaeus lafétra-infection prevention viral infections bacterial infections fred robbins-viral vaccines horace hodes-viral vaccines kempe-smallpox eradication james cherry recipients for the distinguished service award the history of paediatrics nurturing children, a history of pediatrics abt-garrison history of pediatrics thacher t a brief rule to guide the common-people of new england how to order themselves and theirs in the small pocks or measles enquiry into the nature, cause and cure of the angina suffocativa or sore throat distemper an account of the weather and diseases of south carolina rush b an inquiry into the cause and cure of cholera infantum history of pediatrics in the united states pox americana: the great smallpox epidemic of - acute communicable diseases. in: wr bett (ed) the history and conquest of common diseases dewees wp a treatise on the physical and medical treatment of children on the pneumonia of children parrot's pseudoparalysis semi-centennial volume of the american pediatric society osler and children the centennial history of the american pediatric society infectious diseases and the last years in the american pediatric society diphtheria and theories of infectious disease: centennial appreciation of the critical role of diphtheria in the history of medicine the american pediatric society's report of the collective investigation of the antitoxin treatment of laryngeal diphtheria in private practice the first full-time academic department of pediatrics: the story of the harriet lane home the history of cerebro-spinal meningitis in america smith jl a treatise on the diseases of infancy and childhood baker sj fighting for life save the babies: american public health reform and the prevention of infant mortality the diseases of infancy and childhood an american text-book of the diseases of children by american teachers kretchmer n (eds) history of pediatrics - a retrospect and a forecast a historical note on chemotherapy of bacterial infections the first use of an antibiotic in america report of special committee on prophylactic procedures against communicable diseases routine measures for the prophylaxis of communicable diseases history of pediatric hematology oncology whole-genome random sequencing and assembly of haemophilus influenzae rd the first certifying examination in pediatric infectious diseases complete genome sequence of an m strain of streptococcus pyogenes the sequence of the human genome international human genome sequencing consortium initial sequencing and analysis of the human genome childhood vaccine development in the united states ( ) for rapid viral diagnostic methods, ann arvin ( ) for pathogenetic and immunologic studies of herpes viruses, margaret hostetter ( ) for studies of the pathogenesis of candidiasis, and elaine tuomanen table . the first committee on rheumatic fever of the american heart association was organized in , with t. duckett jones (famous for his jones criteria proposed in ) serving as the first chair. over the subsequent years, this committee has expanded its scope to include infective endocarditis and kawasaki disease, and its membership has been weighted heavily to include pediatric infectious diseases experts as well as cardiologists. in contrast to many other organizations, world war ii actually accelerated the activities of this group because of the severity of rheumatic fever and rheumatic heart disease nobel laureates. four members of the american pediatric society (including one honorary member) have been awarded the nobel prize in physiology and medicine, and all of them were recognized for research related to infectious diseases and their prevention. in , thomas weller, frederick robbins, and john enders received the nobel "for their discovery of the ability of poliomyelitis viruses to grow in cultures of various types of tissues." enders, a basic virologist, was elected to honorary aps membership in , and weller and robbins are full members. additionally, d. carleton gajdusek received the nobel "for discoveries concerning new mechanisms for the origin and dissemination of infectious diseases," specifically for the study of kuru and slow virus infections.howland award. the john howland award of the american pediatric society "for distinguished service to pediatrics" was initiated in , and a number of howland awardees have been honored particularly for contributions to the conquest of infectious diseases of childhood. these key: cord- - fhhuzg authors: hoffman, paul s. title: antibacterial discovery: st century challenges date: - - journal: antibiotics (basel) doi: . /antibiotics sha: doc_id: cord_uid: fhhuzg it has been nearly years since the golden age of antibiotic discovery ( – ) ended; yet, we still struggle to identify novel drug targets and to deliver new chemical classes of antibiotics to replace those rendered obsolete by drug resistance. despite herculean efforts utilizing a wide range of antibiotic discovery platform strategies, including genomics, bioinformatics, systems biology and postgenomic approaches, success has been at best incremental. obviously, finding new classes of antibiotics is really hard, so repeating the old strategies, while expecting different outcomes, seems to boarder on insanity. the key questions dealt with in this review include: ( ) if mutation based drug resistance is the major challenge to any new antibiotic, is it possible to find drug targets and new chemical entities that can escape this outcome; ( ) is the number of novel chemical classes of antibacterials limited by the number of broad spectrum drug targets; and ( ) if true, then should we focus efforts on subgroups of pathogens like gram negative or positive bacteria only, anaerobic bacteria or other group where the range of common essential genes is likely greater?. this review also provides some examples of existing drug targets that appear to escape the specter of mutation based drug resistance, and provides examples of some intermediate spectrum strategies as well as modern molecular and genomic approaches likely to improve the odds of delivering st century medicines to combat multidrug resistant pathogens. infectious diseases are a leading cause of death worldwide, yet the miracle antibiotics developed to combat them are being lost to the rapid emergence of drug resistance. modern medicine is heavily dependent on antibiotics that enable many procedures including abdominal surgeries, bone marrow and organ transplants, managing immune compromised patients and cancer patients and for routine hip and knee replacements [ , ] . while one might presume that new antibiotics would be discovered at a sufficient pace to replace those rendered obsolete by resistance, this has not happened. worse, the few antibiotics that recently entered the clinic are derivatives of older drugs and are susceptible to the same existing drug resistance mechanisms. it is hard to imagine that the last new chemical class of antibiotic for treating infections caused by gram negative (superbug) bacteria (gnb) was the quinolones, discovered over years ago. and, it is not much better for the gram positives (gp) with linezolid and daptomycin discovered nearly years ago. while fleming and waksman are well known discoverers of antibiotics (penicillin and streptomycin, respectively), it is unlikely that anyone today knows someone that delivered a new class of antibiotic from bench to clinic. thus, unlike most disciplines of science and technology, there are no experts to advise us. worse, there seems to be no cumulative knowledge gained from the many failures upon which to build a winning strategy [ ] . while it has been argued that the discovery of antibiotics is one of the greatest achievements in medicine in the th century; our failure to build a sustainable antibiotic discovery platform has left us with one of the greatest liabilities, and now in the st century, one of the greatest challenges. some blame the lack of funding or of effort, but in retrospect the effort was substantial, particularly by the pharmaceutical industry in the 's, and most agree that massive investments would have made little difference. while much has been written recently to explain these failures [ ] [ ] [ ] [ ] ; few have provided tactical approaches that might fare any better [ ] . emergence of drug resistance remains the greatest concern and biggest challenge to future discovery efforts. many believe it is impossible to create an antibiotic to which bacteria cannot evolve resistance and based on some recent experience, the therapeutic window for any new one is projected to be less than five years-a major disincentive. if indeed antibiotic resistance (mutation-based drug resistance) is the major challenge; then, why have we not focused on identifying drug targets less prone to mutation-based resistance? with scarce resources and many suggestions for how to find next generation antibiotics, where do you place your bets [ ] ? this review examines current discovery approaches and their intrinsic liabilities; challenges some myths associated with antibiotic resistance; and concludes by exploring promising st century discovery strategies along with some examples of antibacterials that might escape the specter of drug resistance. there are many headwinds and challenges to antibacterial discovery and delivery of new medicines to the clinic that are not discussed herein (societal, regulatory and marketing) that readers are directed elsewhere for more comprehensive coverage [ ] [ ] [ ] [ ] . most of the antibiotics used in the clinic today were derived from natural products (np) identified in screens of environmental material using variations of the waksman platform strategy [ ] . synthetic antibacterials trace back to paul ehrlich who identified chemical compounds like salvarsan that was active in the treatment of syphilis. later, domagk discovered the dye prontosil and its active metabolite sulfanilamide that inhibited folic acid biosynthesis. this work led to development of the sulfa drugs [ ] . medicinal chemistry and the advent of high throughput screens of compound libraries (target based) replaced np searches in the mid 's and reintroduced the idea of synthetic chemistry as a strategy for creating next generation antibacterials. advances in computational biology (bioinformatics, systems biology, and metagenomics) and structural biological technologies (crystal structures of protein targets, ligand screens via docking software, the so called designer drug strategy) have led to a third discovery strategy-synthetic biology. while all these technologies engender some optimism, the main reason for the antibiotic discovery void in the first place is that creating new chemical classes is really hard. is repeating history a viable strategy?-probably not. one definition of insanity is repeating the same task over and over again while expecting a different outcome. this is especially applicable to antibiotic discovery research where much emphasis has been placed on finding new natural product (np) antibiotics [ ] . after all, the vast majority of antibiotics used in the clinic are derivatives of nps. the insanity with continuing on this path is that for all of these np antibiotics, resistance mechanisms predated their therapeutic use and this is unlikely to change [ , , ] . moreover, we know from past discovery efforts that nps tend to be redundant-with the same targets and mechanisms of action appearing over and over again [ ] . casting a wider net will not change this reality, because the number of broad spectrum drug targets is quite small [ ] . hypothesis. the number of antibiotic classes is limited by the number of broad spectrum drug targets. it follows that the number of resistance mechanisms will generally parallel the number of antibiotic classes. hence, modifying the genes associated with secondary metabolism, while potentially improving an existing scaffold, is unlikely to produce new chemical classes of antibacterials. another issue with nps is that since they have evolved in natural environments and not in the human milieu, most nps are structurally complex and as such are by default poor pharmacophores (pk/pd), requiring much medicinal chemistry to improve bioavailability, to reduce drug metabolism or to reduce intrinsic toxicities. the pharmaceutical industry abandoned np divisions long ago in favor of high throughput screens of compound libraries against novel drug targets (another failure, see below); or, more productively to create next generation derivatives of existing antibiotics, a strategy that has worked well and continues today as judged by the number of analogues in the current pipeline. despite the continuum of second, third and fourth generation β-lactams (penicillin, cephalosporin and carbapenem derivatives) [ ] , by far the largest group of antibiotics used in the clinic today, has not solved the resistance problem originally pointed out by alexander fleming in the late 's. while logic dictates that we should abandon further development of this class, advances in pairing them with β-lactamase inhibitors (clavulinate, avibactam, and vaborbactam to mention a few) has restored their effectiveness and extended their clinical lifetimes [ ] . since β-lactamases and β-lactam targets (penicillin binding proteins, pbp) share conserved structural attributes that can be altered via mutation, resistance will eventually defeat them, but for now this strategy is both viable and profitable. the current antibacterial pipeline is populated with new derivatives based on the scaffolds for quinolones, tetracyclines, macrolides and aminoglycosides [ ] . new chemistries around existing scaffolds has the potential to overcome current resistance mechanisms by improving binding complexity with the drug target, and or improve pharmacological properties. in this regard, the ketolides were supposed to overcome resistance to macrolides, but the tradeoff is increased toxicities. however, given our experiences with np antibiotics in general, it is unlikely that continued searches for new ones, regardless of where one looks, will be any more successful than past efforts. in the mid 's, the pharmaceutical industry turned to molecular biology and genomics to sort through microbial genomes for novel drug targets that could be cloned and their products configured into assays amenable to robotic high throughput screens of massive compound libraries (target-based platform). after all, new medicines were found in library screens in other therapeutic areas, including antivirals [ ] . the fatal assumption in antibacterial screens was the belief that antibiotic-like material was present in these chemical libraries [ ] [ ] [ ] [ ] . in reality, they contained little that resembled antibiotics, because antibiotics are often of high molecular weight and far more complex than can be synthesized by chemists. worse, most of these compounds were poor pharmacophores (hydrophobic with poor pk/pd properties) and failed both lipinski's rule of five and hergenrother's rules for penetration of gn bacteria [ ] [ ] [ ] . unfortunately, efforts to assemble libraries composed of more "antibiotic like material" have yet to deliver an antibacterial to the clinic. what does "antibiotic like" really mean anyway? the experiences of glaxosmithkline, astrazeneca and others are well documented and today there seems to be little enthusiasm for revisiting this approach [ , , ] . however, the lists of potential therapeutic drug targets identified in these bioinformatics initiatives and others remain to be exploited. one of the targets in the gsk screen, fabi, an enoyl-acp reductase and rate-limiting step in fatty acid biosynthesis is the target of a novel therapeutic (afabicin, formerly debio- ) that is active against staphylococcus [ ] . importantly, the failure of hts to deliver new therapeutics to the clinic should not be confused with whether or not synthetic antibacterials can be developed de novo as part of a rational or designer drug strategy (see later section). every healthcare worker can tell you why antibiotic resistance is bad for patients and why antimicrobial stewardship (judicious use) is so important, but few have any deep understanding of the diversity of underlying molecular and genetic mechanisms. this has created a "chicken little" effect; where strong opinions based on shallow thinking, perpetuation of myths and intolerance of new ideas have unnecessarily complicated the discovery process. much of antibiotic theory has evolved over nearly years of history and mostly from experiences with nps. antibiotics and their respective resistance mechanisms have co-evolved over millions or even billions of years of internecine microbial warfare that is ongoing in the environment. these resistance mechanisms are encoded in dna and can be disseminated throughout the microbial world via mobile genetic elements and horizontal transfer [ ] . it is not surprising that soil and aquatic microbes transfer these resistance determinants to human and animal pathogens, often in clinical settings where antibiotics are in heavy use. there is no good outcome to the continued use of nps and as discussed previously it is unlikely that new ones will fare any better. this is best exemplified by the emergence of resistance (mcr- family) to colistin, a polymyxin class antibiotic that has been around for decades, but little used, until the emergence of carbapenem resistance in klebsiella (kpc) and other carbapenem resistant enteric superbugs (cre) made it the drug of last resort [ ] . the rapid and global emergence of mcr- just underscores the point. the resistance problem is further exacerbated by globalization, increasing population density and international travel that has brought us mcr- as well as the ndm- β-lactamase resistance determinant [ ] . the covid- pandemic, unfortunately, is another example of the accelerated global spread of biological agents. it follows from the previous paragraph on nps, that synthetic antibacterials that inhibit targets "mother nature" has yet to find would require millions of years of evolution for resistance determinants to emerge. note that this hypothesis also holds true for new chemistries against established drug targets, provided that they are also not susceptible to existing resistance mechanisms. a good example is linezolid, a synthetic antibacterial discovered nearly years ago and more recent derivatives (tedizolid), that inhibit protein synthesis in gp bacteria [ ] . one might think that synthetic antibacterials would enjoy a long clinical life. unfortunately, synthetic classes of antibacterials, including linezolid, are often defeated by mutation-based drug resistance. mutations occur naturally (probability of~ in ) in dna and since microbial infections involve hundreds of billions of bacteria, microbes tend to win the probability game. survival is the prime directive for any lifeform and in particular, the stress of antibiotics on bacteria, especially at sub-inhibitory levels, provides strong selection for these resistant variants to emerge and flourish. it should be pointed out that mutation-based drug resistance also underlies resistance for nearly all nps. this reality led eric lander and john p. holdren to conclude in a summary of their report by the committee on antimicrobial resistance to the president's council on science and technology that: "in the fight against microbes, no permanent victory is possible: as new treatments are developed, organisms will evolve new ways to become resistant" [ ] . this grim prediction is certainly supported by a recent clinical trial of promising synthetic boron containing heterocycle leucyl trna synthetase inhibitor which was halted due to rapid emergence of drug resistance [ ] . this novel drug inhibited a non-essential proof-reading region of the essential enzyme in which mutations could accumulate and thereby defeat the inhibitor without total loss of function [ ] . the lessons learned here include: ( ) focus on the essential catalytic center of a prospective drug target, ( ) ensure amino acid conservation within this region (resists mutation), and ( ) confirm by co-crystallization that leads indeed are binding within the catalytic pocket of the target. it is also helpful early on to explore possible off target activities against human drug targets related to a particular enzyme class. attention to these details might lead to medicines that slow the inevitable pace to drug resistance. it raises another critical question "can we find drug targets that by catalytic mechanism are capable of escaping mutation-based drug resistance? targets that might defeat mutation based drug resistance do exist. one example is the lipid ii and lipid iii targets associated with cell wall biosynthesis [ ] . these targets are composed of lipid and not amino acids and are the target of a new np antibiotic teixobactin that is in early clinical development for treatment of infections caused by gp bacteria [ ] . another type of target that had not been previously considered is pyruvate: ferredoxin oxidoreductase (pfor) whose catalytic center is highly conserved through evolution and for which there are no np inhibitors [ ] . the pfor catalytic mechanism involves a uniquely positioned and contorted vitamin cofactor (vitamin b or thiamine pyrophosphate, tpp) [ , ] . redox cycling via iron/sulfur centers activates the vitamin to enable binding of substrate pyruvate. the nitrothiazolide class of synthetic antibiotics (fda approved nitazoxanide and analogue amixicile in clinical development) deactivates the vitamin via a proton abstraction mechanism that is dependent on a functional enzyme [ , ] . two key points here are that mutations to the enzyme (loss of function) or that alter the vitamin, a small molecule, are lethal ( ). tpp is also a cofactor in many enzymes (pyruvate dehydrogenase [pdh] and pyruvate carboxylase), but these are not inhibited by nitazoxanide or amixicile [ , ] . importantly for nitazoxanide, there are no toxicities in humans or mitochondria which lack the drug target. importantly, in over years of clinical use, there are no reports of drug resistance with nitazoxanide. a hint at possible resistance to nitazoxanide comes from studies of lab generated resistant mutants of human parasite giardia, where whole genome sequencing found no single correlating mutation among resistant strains [ ] . from this study and others, it is possible to suggest that second site compensatory mutations may lead to metabolic shifts that produce a "tolerance like phenotype", much like over expression of efflux systems incrementally raise mic for quinolones. is this evolution at work? it could be, as efflux buys time for mutations in gyrase and topoisomerase genes to manifest. alternatively, as noted with nitazoxanide tolerance in helicobacter pylori, it may be an example of the microbe "faking it", i.e., tinkering with limited metabolic regulatory choices to enable survival [ ] . in this case, tolerance can be overcome by increasing the therapeutic dose, i.e., one that the microbe cannot overcome by tinkering. the jury is still out though, as only time will tell if such tolerance mechanisms can be inherited. there are several caveats from the pfor example that might be useful in identifying new targets: ( ) pfor is an ancient enzyme highly conserved through evolution; ( ) the vitamin cofactor is uniquely positioned and tightly bound within the enzyme; ( ) the critical amino acids required for cofactor function are absolutely conserved based on analysis of available sequences of pfor enzymes (> ) despite whether pfor is a dimer of high molecular weight monomers or like in helicobacter pylori, a dimer comprised of multiple subunits [ ] ; and ( ) all of these traits are found in the entire broad family of the alpha-keto-acid oxidoreductases (multiple essential targets). perhaps most important in this example is that nitazoxanide and amixicile work by a "theft" mechanism that requires a functional enzyme and cofactor. the phenotype to the affected pathogen is one of slow starvation (pyruvate) with no definable selective mechanism or means to overcome inevitable death by starvation. in retrospect, few searches for new drug targets considered mutation frequency as a criterion for prioritization. finding catalytic centers that are highly conserved and potentially druggable can be relatively straightforward, but like pfor, would likely yield targets of limited spectrum. "highly conserved" generally means that mutations in these regions lead to loss of function or lethality. these potential targets can be catalogued by comparative genomics (blastp approach) by comparing genomes (gene products) from a target group of pathogens. by setting the probably of the match (identity) bar to be more stringent (e − or e − ) creates a shorter list of protein matches whose amino acid sequences are highly conserved [ , ] . further analysis would include amino acid conservation within the catalytic center along with other evaluative criteria that includes chemical space, catalytic mechanism, participation of cofactors and uniqueness from orthologues found in humans or mitochondria. crystal structure of the enzyme is crucial in this process and in silico screening of chemical libraries becomes an early first step in finding developable leads. a number of recent examples can be used to guide this process [ , , ] . the power of computational biology and chem-informatics has yet to be fully exploited, so this area has room to grow. an advantage of this approach is that objective criteria replace age old empiric rationale (guesswork) in choosing drug targets. however, the reality of finding new broad spectrum drug targets is close to nil. this is because microbial genomes are small and the major targets for broad spectrum antibiotics are already known (protein synthesis, dna and rna synthesis, cell wall biosynthesis and a few central metabolic pathways) [ ] [ ] [ ] [ ] [ ] . as discussed below, we need to consider targets of more limited spectrum. the number of broad spectrum drug targets among microbes that meet the criteria of essential and non-redundant is predicted to be quite small, perhaps fewer than several hundred [ , ] . most targets are already known and come with the baggage of preexisting antibiotic resistance mechanisms and the reality that they will cause collateral damage to normal flora when deployed. the problem with narrow spectrum antibiotics is that clinicians do not use them when the pathogen responsible for an infection is not known or is potentially polymicrobial. broad spectrum antibiotics are a hedge and provide liability coverage in the event of an adverse outcome. this reluctance also plagues new antibacterials that enter the clinic, another headwind to drug development. ironically, getting a new broad spectrum antimicrobial through the food and drug administration (fda) today is nearly impossible because for each indication a separate clinical trial is generally required and the additive costs are prohibitive. antibacterials currently in clinical development (gepotidacin) and those that have recently entered the clinic like oritavancin, dalbavancin and tedizolid are examples where the potential use is purposefully limited [ ] . in the distant past, the spectrum for an antimicrobial was often established by the process of "off label" use (trial and error), but today, hospital practice/malpractice and liabilities have essentially ended this strategy. we can expect in the future that the number of indications for antibacterials will continue to be limited by development costs [ ] . perhaps a more productive antibacterial strategy is to focus on groups of microbes sharing common essential drug targets as exampled by pfor. in this example, nitazoxanide exhibits the same spectrum as metronidazole, providing broad anaerobic coverage (gp and gn), treatment of infections caused by anaerobic human parasites and potentially treatment of infections caused by members of the epsilon proteobacteria (helicobacter and campylobacter). along these lines, developing antimicrobials that target either gp or gn bacteria would exploit new drug targets unique to each, such as teixobactin for gpb. similarly, drugs that are selective against mycobacterium tuberculosis are highly desirable since resistance is a major problem [ ] . recent new chemical classes of anti-tubercular therapeutics include the nitroimadazole delamanid that targets the f deazaflavin nitroreductase [ ] . similarly, pathogen selective therapeutics such as ridinilazole, a novel synthetic drug in clinical development for treatment of colitis caused by clostridioides difficile, are developed in response to an urgent clinical need [ ] . in this case, ridinilazole targets cell division by an unknown mechanism that is likely to uncover a novel drug target and mechanism. microbiome studies support limited collateral damage with ridinilazole and the frequency of drug resistance appears to be low [ ] . since there is an urgent need to develop gn-selective therapeutics, focusing on targets unique to them and vetted by objective criteria (including resistance to mutation) should be encouraged. indeed, ongoing drug discovery efforts are targeting lps biosynthesis (lpxc, lepb, msba) [ ] , essential enzymes associated with beta-barrel assembly machine (bam), lipoprotein assembly (lol), and even the periplasmic disulfide bond isomerase (dsba, dsbc, dsbd) enzymes [ ] [ ] [ ] [ ] [ ] . unfortunately, lead compounds targeting lps biosynthetic systems have proven toxic and reminds us that finding new chemistries of low toxicity remains a significant challenge. focus on anti-virulence strategies, particularly for gn superbugs, is now gaining momentum as inhibitors are emerging against secretion systems, pili, motility, quorum sensing and toxins [ , ] . conceptually, if virulence systems contribute to antibiotic resistance or tolerance, inhibition of these systems might result in regulatory changes that restore or enhance susceptibility to mainline antibiotics. as better rapid diagnostics come onboard, narrow or limited spectrum antibacterials will see increased usage, and when treating polymicrobic infections, therapeutic strategies would likely mix and match the appropriate therapeutics. even better, we might consider creating bi-functional or hybrid antibacterials that provide dual function that likely will extend both coverage and timelines to resistance. repurposing of drugs, especially fda approved medicines, for use as antibacterials has gained in interest since they skip the early preclinical and clinical development stages [ ] . it is also believed that such drugs would also come with novel modes of action and perhaps escape preexisting drug resistance mechanisms. perhaps the most studied of these compounds is auranofin, a drug developed to treat rheumatoid arthritis and cancer, that is a potent inhibitor of thioredoxin reductase found in many human pathogens including clostridioides difficile [ ] . for repurposed drugs in general the primary indication is still a secondary target of the new application. in order to gain therapeutic efficacy (serum levels greater than mic), repurposed drugs would likely be administered at concentrations exceeding levels required for efficacy of the original use. in reality, drugs that actively target human enzymes, often come with undesirable side effects or toxicities. still, for treatment of infections such as tuberculosis, gonorrhea or by c. difficile and h. pylori, repurposed drugs in combination with other therapeutics might aid overcoming drug resistance. the goal of this review was to point out basic science challenges to the discovery of new classes of antibacterials and to provide some suggestions on how to move forward in a more productive manner. we know that the "waksman platform" for discovery of new nps and the "hts-target based platform" for screening chemical libraries have both failed to deliver new antibacterials. does repeating these strategies boarder on insanity? from a business perspective, investment in antibacterial discovery is mitigated by concerns over rapid emergence of drug resistance and loss of investment. if indeed mutation-based drug resistance is the greatest impediment to the discovery effort, then why not work backwards from the problem as a discovery strategy? this review provides a few examples of such drug targets (pfor and lipid ii) and respective inhibitors that shows that this approach has merit. structure based drug design has yielded therapeutics in other areas including hiv/aids (protease inhibitors), antivirals (zanamivir for influenza), and even inhibitors of cyclooxygenase, so why not for antibacterials? bioinformatics can be used to collate essential targets and provide a probability score for evaluating risk for mutation based drug resistance. structure based drug design tools have been steadily evolving and their use in evaluating three dimensional structure and chemical space for ligand binding can be integrated with in silico screens of synthetic chemical libraries to produce early leads. lead optimization and structure activity relationships (sar) can be modeled and synthetic chemistry and chem-informatics can be used to optimize candidates in areas of pk/pd, drug metabolism and toxicology, essential to building safe medicines. it should be obvious that antibacterial development in the future will require a wide range of biological, chemical, computational and pharmacological disciplines working towards a common goal to progress st century medicines. while the pharmaceutical industry used to contain this expertise, we need to find a way to fund such initiatives that also removes the shareholders and corporate return on investment metrics from the equation. while carb-x and other related initiatives are critical in the clinical development of antibacterials via cost sharing with startup companies, the real bottleneck occurs much earlier in the early discovery process. if years of effort has not yielded a novel class of gn therapeutic, one might imagine the failure rate for any new initiative might be close to %, not a viable strategy for "bean" counters. we have to ask "how much are we willing to invest in order to get one new antibiotic to the clinic?" we already know many ways not to make an antibiotic, perhaps now we can find more creative and imaginative ways to produce them. perhaps if we present the antibiotic crisis as on the scale of the covid- pandemic, maybe it would engender greater attention and resource allocation. funding: this research received on external funding. the author declares on conflict of interest. who will develop new antibacterial agents? attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the eu and the european economic area in : a population-level modelling analysis antibacterial drug discovery: some assembly required challenges of antibacterial discovery revisited drugs for bad bugs: confronting the challenges of antibacterial discovery eskapeing the labyrinth of antibacterial discovery challenges of antibacterial discovery time for a change: addressing r&d and commercialization challenges for antibacterials towards a new business models for r&d for novel antibiotics. drug resist a comprehensive regulatory framework 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against clostridium difficile in a mouse infection model resistance formation to nitro drugs in giardia lamblia: no common markers identified by comparative proteomics helicobacter pylori porcdab and oordabc genes encode distinct pyruvate:flavodoxin and -oxoglutarate:acceptor oxidoreductases which mediate electron transport to nadp systematic identification of selective essential genes in helicobacter pylori by genome prioritization and allelic replacement mutagenesis antibactr: dynamic antibacterial-drug-target ranking integrating comparative genomics, structural analysis and experimental annotation approaches to the structure-based design of antivirulence drugs: therapeutics for the post-antibiotic era design, synthesis biological and evaluation of novel aryldiketo acids with enhanced antibacterial activity against multidrug resistant bacterial strains rational design of drug-like compounds targeting mycobacterium marinum melf protein postgenomic strategies in antibacterial drug discovery antibacterial drug discovery in the resistance era antibacterial discovery and development-the failure of success? antibiotic discovery: where have we come from, where do we go? antibiotics an overview of new antitubercular drugs, drug candidates, and their targets from discovery to its use for pulmonary multidrug-resistant tuberculosis (mdr-tb) ridinilazole: a novel antimicrobial for clostridium difficile infection enhanced preservation of the human intestinal microbiota by ridinilazole, a novel clostridium difficile-targeting antibacterial, compared to vancomycin countering gram-negative antibiotic resistance: recent progress in disrupting the outer membrane with novel therapeutics a novel inhibitor of the lolcde abc transporter essential for lipoprotein trafficking in gram-negative bacteria monoclonal antibody targeting the β-barrel assembly machine of escherichia coli is bactericidal disrupting gram-negative bacterial outer membrane biosynthesis through inhibition of the lipopolysaccharide transporter msba the small molecule nitazoxanide selectively disrupts bam-mediated folding of the outer membrane usher protein thinking outside the bug: molecular targets and strategies to overcome antibiotic resistance defeating antibiotic-resistant bacteria: exploring alternative therapies for a post-antibiotic era drug repurposing for the treatment of bacterial and fungal infections repurposing auranofin as a clostridioides difficile therapeutic key: cord- -ytjctt authors: kushnir, vitaly a.; kashani, banafsheh; adashi, eli y. title: reproductive healthcare during a pandemic: a new york state of mind date: - - journal: reprod biomed online doi: . /j.rbmo. . . sha: doc_id: cord_uid: ytjctt the purpose of this commentary is to assess whether the designation by new york state department of health of “sexual and reproductive health services as essential” is consonant with the seemingly divergent objectives of providing patient-centered care and advancing national public health objectives in the resource-constrained setting of a global pandemic. sexual and reproductive health services deemed essential included: contraception, fertility treatments, gynecologic surgeries, abortion services, obstetrical care, treatment of sexually transmitted diseases, gynecologic and breast care. in addition, the new york department of health took care to emphasize that the "ultimate decision on when such services must occur is between a patient and clinical provider." it is the purpose of this article to assess whether the designation of "sexual and reproductive health services as essential" is consonant with the seemingly divergent objectives of providing patient-centered care and advancing national public health objectives in the resource-constrained setting of a global pandemic. the remarkable position taken by new york state must be viewed in the context of the response to the covid- pandemic, which illuminated multiple deficiencies in the u.s. healthcare system. the rapid shift from patient-centered care to a national public health campaign has presented complex ethical dilemmas and challenged the very core of the moral values of clinicians (ethical framework for health care institutions responding to novel coronavirus sars-cov- (covid- )). frontline healthcare professionals have simultaneously faced physical danger due to scarcity of personal protective equipment and deteriorating economic conditions due to strain placed by the pandemic on the entire u.s. healthcare system. to-date, the centers for disease control and prevention (cdc) reported over , infections among of u.s. healthcare workers; tragically, many lost their lives in their line of duty. in this challenging environment, regulatory agencies including the cdc and many state departments of health have called for the suspension of "elective" and "non-essential" medical services. in a number of states, including texas and ohio, reproductive healthcare, including abortion services, were all but suspended under such decrees (bayefsky et al. ) . as such, these drastic steps risk rolling back much of the progress that has been achieved in reproductive medicine and in reproductive rights over the past generation. viewed in this context, the policy directive issued by new york state stands out as exceptional. even in its darkest hour, the state of new york elected to declare reproductive health services as "essential." the rationales advanced for the discontinuation of reproductive healthcare services emphasized the importance of preventing the diversion of critical resources from hospitals and of minimizing the contagion though social distancing. both arguments, however, are misguided. after all, most reproductive healthcare encounters take place in an ambulatory setting and thus do not divert significant critical resources away from the care of covid- patients in hospital settings. moreover, the postponement of reproductive care is likely to prove counterproductive by potentially exacerbating both the acuity and severity of extant and evolving reproductive conditions. women faced with abnormal uterine bleeding, endometriosis, and ectopic gestation can be successfully managed in an ambulatory setting rather than in emergency and hospital operating rooms. delayed access to contraception and abortion services is particularly troubling since unintended pregnancies result in termination at later stages when the risks of complications are substantially higher (bayefsky et al. ) . alternatively, women who are denied abortion services and instead continue their undesired pregnancies, will require significant ongoing healthcare resources, especially obstetric and neonatal care. the most vulnerable women, who already face disparities in the access to healthcare, will likely be disproportionately affected by delayed access to care. finally, ambulatory practices have rapidly implemented steps to mitigate the risk of contagion by offering telemedicine for nonurgent consultations, enhanced hygiene protocols, infection screening prior to clinical encounters, and social distancing of patients and staff in public areas. collectively, these efforts minimize the risk of infection for patients and clinical staff, without interrupting critical patient care in an ambulatory setting. several professional associations have gone on record to articulate official positions consonant with the position promulgated by new york state. in its official statement, the american academy of family physicians (aafp) notes that "we must remain patient-centric and recognize that delaying care has immediate impacts on the health of the woman... physicians … should be trusted to make decisions in the best interest of their patients". similarly, the american college of obstetricians and gynecologists (acog) recommended that gynecologic patients be triaged based on the urgency of the condition while "ensuring that patients who are pregnant or considering becoming pregnant have the patient-centered, safe care they need". acog also voiced unequivocal support for continued access to 'essential' and 'time-sensitive' abortion services, and emphasized that "the consequences of being unable to obtain an abortion profoundly affects a person's life, health, and well-being." finally, not only has acog demonstrated its continued support for women's reproductive rights and access to care, it went on to offer detailed guidance to providers with an eye toward attenuating the risk of infection within their practices. while early in the pandemic both american and european reproductive medical societies took a cautious approach and advised the postponement of most non-urgent infertility treatments, as more data about the virus emerged, these organizations position has shifted. in a recent joint statement the american society for reproductive medicine (asrm), the international embryology (eshre) have concluded that "reproduction is an essential human right that exists regardless of race, gender, sexual orientation or country of origin" and that "reproductive care is essential". the affordable care act (aca) has notably improved access to reproductive healthcare in the realm of family planning and pregnancy termination (daw and sommers, ) . however, comprehensive support for specialized reproductive services such as infertility care was not included in the aca. in its progressive quest to address unmet reproductive needs, new york state has taken to address this void as well by passing insurance laws § § (k)( )(c) and empowering frontline physicians to determine the best course of action is beneficial not only for individual patients, but, in the context of essential reproductive healthcare, is also consistent with advancing public health. an alteration in this course of action, may result in the recession of women's rights which could take decades to reverse. the healthcare system must thus rely on its dedicated frontline healthcare professionals to continue providing patientcentered care while acting in the best interest of the public. these frontline providers deserve the full trust and support of the nation, its states, and its professional organizations. once the current crisis abates, one would hope that the healthcare community and the regulatory bodies thereof will follow new york's lead thereby uniting around the simple truth, that reproductive healthcare is essential, and that decisions concerning its exercise are best left to the patient and her provider. abortion during the covid- pandemic -ensuring access to an essential health service faqs for obstetrician-gynecologists, gynecology; american college of obstetricians and gynecologists  covid- and human reproduction joint statement: asrm/eshre/iffs the affordable care act and access to care for reproductive-aged and pregnant women in the united states  ethical framework for health care institutions responding to novel coronavirus sars-cov- (covid- ). the hastings center sexual and reproductive health services during the covid- public health emergency academy of family physicians support of continued access to reproductive health services during the covid- pandemic united nations key: cord- -hs sodyt authors: adams hillard, paula j. title: “pediatric and adolescent gynecologic problems continue during the covid- pandemic” date: - - journal: j pediatr adolesc gynecol doi: . /j.jpag. . . sha: doc_id: cord_uid: hs sodyt nan greetings, dear readers, from shelter-in-place covid-land, a very different place from where we all were (literally, and figuratively) when i wrote my last editorial on pediatric and adolescent gynecology (pag) in the time of a pandemic. most of us are still reeling from the many changes that covid- infections have necessitated. some of you may have been infected yourselves. others have had family members who were infected, and some of you have undoubtedly lost friends, colleagues, family members, or patients to complications of the viral infection. my heart goes out to you. this is a time of tragedies. together we mourn. the economic consequences of the pandemic are also widespread and devasting, particularly to our most vulnerable populations-people of color and those who are economically disadvantaged. when i chose to go to medical school, i remember thinking that i would always have a job. illness and suffering are part of the human condition, and physicians, nurses, and other healers have been needed throughout time, and are especially needed today. some of you who care for adults as well as children and teens are still in the thick of covid- infections. i am fearful that the policies of "opening up" that are being promoted by many politicians are happening in the context of still rising rates of infection. when we listen to the authorities who base their recommendations on science, we hear that the effect will be even greater numbers of infections and deaths. the current effect of covid- on our pag patients here in california is determined by the fear that parents have of coming to our offices and hospitals. covid infections in the san francisco bay area appear to have peaked, and the surge in adult patients was mostly avoided through early shelter-in-place orders. fortunately, children and teens appear to have less severe infections, although concerns about specific morbidities are being raised. but unfortunately, "routine" healthcare is now being neglected, sometimes with the results that patients with emergent problems are presenting later than they otherwise would. while our operating rooms are now open, patients and families are still deferring the surgeries that had been postponed. i am eager to institute some of the elements of enhanced recovery after surgery that are described in this issue of the journal of pediatric and adolescent gynecology (jpag). our patients are still experiencing the usual pag concerns that are also addressed in this issue: symptomatic labial adhesions, prepubertal vaginal bleeding, chronic pelvic pain, sexually transmitted infections, issues related to contraception and induced abortion, [ ] [ ] [ ] [ ] [ ] [ ] adnexal masses, , differences of sex development, and müllerian anomalies, , among many other problems. the naspag position statement, published in this issue, highlights the ongoing reproductive health needs of adolescents during a pandemic, including the need for contraception and confidential healthcare, even when using telehealth platforms. this issue's review article on dating violence and its implications for girls' sexual health provides definitions of dating violence and its many manifestations, estimates of prevalence, and reminders of the severe consequences of morbidity and mortality, but also the complex links with behaviors. the author notes that adolescent girls with a history of sexual coercion are more likely to engage in sexual risk behaviors and vice versa. this review reminded me of past pag patients. i recall from years ago, the saga of a physician's daughter who was terrified of her ex-boyfriend, who was stalking her. the psychological aggressions that she described included manipulation and coercion, which she ultimately recognized. reproductive coercion may not always be recognized. one of the reasons that i devised my structure of a first gynecologic visit in which i speak first with the adolescent and her parent (usually mom), then with the parent(s) with the teen, and subsequently with the adolescent confidentially, completing the visit with a summary of the visit (sometimes with parameters elicited from the teen about what is permissible to share with the parent) is that i learned how valuable the parent's perspective can be. i remember one of the first moms who opened my eyes to the value of a parent's perspective when mom described her daughter's boyfriend as belittling her and undermining her daughter's self-esteem. i realized that had i spoken only to the daughter, i might not have heard that assessment. experts tell us that during the pandemic, intimate partner violence and child abuse may be more easily hidden with families in isolation. , the pandemic is clearly leading to high levels of stress, and more domestic violence may be the result. we need to keep these issues in mind; as physicians, we may be the only ones to observe these effects. ap-norc poll: pandemic especially tough on people of color. the new york times as states rush to reopen, scientists fear a coronavirus comeback. the new york times enhanced recovery after surgery in pediatric and adolescent gynecology: a pilot study labial adhesion: new classification and treatment protocol vaginal bleeding in pre-pubertal females lack of data-driven treatment guidelines and wide variation in management of chronic pelvic pain in adolescents and young adults prevalence of sexually transmitted infections and risk factors among young people in a public health center in brazil: a cross-sectional study communication about contraception with adolescent females with asthma in pediatric visits the impact of an adolescent gynecology provider on intrauterine device and subdermal contraceptive implant use among adolescent patients benefits of selfadministered vaginal dinoprostone hours before levonorgestrel-releasing intrauterine device insertion in nulliparous adolescents and young women: a randomized controlled trial patient satisfaction with iud services in a school-based health center: a pilot study postpartum contraceptive use among denver-based adolescents and young adults: association with subsequent repeat delivery induced abortion according to socioeconomic status in chile aggressive b-cell lymphoma involving the appendix and bilateral ovaries in an -year-old girl giant paratubal serous cystadenoma in an adolescent female: case report and literature review disorder of sex development: a case of late-diagnosed ovotestis and its postsurgical follow-up assisted reproductive techniques and pregnancy results in women with mayer-rokitansky-k&#xfc;ster-hauser syndrome undergoing uterus transplantation: the czech experience resection of longitudinal vaginal septum using a surgical stapler dating violence in adolescence: implications for girls' sexual health family involvement in the gynecologic care of adolescents domestic violcence calls mount as restrictions linger: 'no one can leave'. the new york times the coronavirus could cause a child abuse epidemic. the new york times key: cord- -qd asgg authors: wilson, n.; baker, m. g.; eichner, m. title: estimating the impact of control measures to prevent outbreaks of covid- associated with air travel into a covid- -free country: a simulation modelling study date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: qd asgg aims: we aimed to estimate the risk of covid- outbreaks associated with air travel from a country with a very low prevalence of covid- infection (australia) to a covid- -free country (new zealand; [nz]), along with the likely impact of various control measures for passengers and cabin crew. methods: a stochastic version of the seir model covidsim v . , designed specifically for covid- was utilized. it was populated with data for both countries and parameters for sars-cov- transmission and control measures. we assumed one australia to nz flight per day. results: when no interventions were in place, an outbreak of covid- in nz was estimated to occur after an average time of . years ( % uncertainty interval [ui]: . - . ). however, the combined use of exit and entry screening (symptom questionnaire and thermal camera), masks on aircraft and two pcr tests (on days and in nz), combined with self-reporting of symptoms and contact tracing and mask use until the second pcr test, reduced this risk to one outbreak every . years ( . to ). if no pcr testing was performed, but mask use was used by passengers up to day in nz, the risk was one outbreak every . years. however, days quarantine (nz practice in may ), was the most effective strategy at one outbreak every . years ( . to ); albeit combined with exit screening and mask use on flights. conclusions: policy-makers can require multi-layered interventions to markedly reduce the risk of importing the pandemic virus into a covid- -free nation via air travel. there is potential to replace -day quarantine with pcr testing or interventions involving mask use by passengers in nz. however, all approaches require continuous careful management and evaluation. the covid- pandemic has had major international health impacts during , with . million cases and , deaths globally by june ( ). in many countries, border controls have been used to limit pandemic spread and this (combined with fear of the pandemic) have markedly reduced international travel. this reduction in travel has contributed to adverse economic and social impacts for countries by reducing business interactions, tourism and movements of international students. new zealand is one of the few countries that has eliminated transmission of the sars-cov- pandemic virus within its borders in line with the goal it adopted to achieve this ( ) . some australian states may also be approaching elimination status, but for australia as a whole, elimination might not be achievable and the country might persist with a suppression strategy until a vaccine is widely available. nevertheless, quarantine-free travel between the two countries is a goal envisaged by the we identified plausible control measures from the published literature and also an online review of strategies identified by an iata medical advisory group ( ) . these controls are shown in figure and table . we simulated one flight per day from australia to new zealand, carrying passengers and cabin crew members. a wide range of aircraft were used on this route in the pre-pandemic era with common ones being the boeing - which takes passengers and the airbus a - with passengers. we used the minimum ratio of one cabin crew member to seats (as required by some regulators), on the assumption that there might be new processes that reduce crew workloads (e.g., meals/drinks placed on seats in advance). this is a small proportion of the level of travel in the pre-pandemic time (i.e., . % of the of , , visitor arrivals from australia to new zealand in the year to january ( ) ). there are several publications that suggest transmission of sars-cov- on aircraft. one reported on patients who "were diagnosed after having flown together in the same flight with no passenger that could later be identified as the source of infection" ( ) . another reported a single case "most likely acquired during a flight" ( ) . but a flight with an index patient who had a dry cough when onboard did not appear to spread infection to any of the approximately passengers ( ) . an iata document ( ) has reported a number of flights with passengers with sars-cov- infection who apparently infected no other passengers, but also one uk to vietnam flight with "up to people" infected. also, based on an iata survey of four airlines it was reported that: "there was one possible secondary passenger case identified in the total, along with just two crew cases, thought to be the result of possible in-flight transmission" ( ) . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint also, of note is that there has been a covid- outbreak in zhejiang province, china on a bus ( ) : passengers on the same bus as the index case had an infection risk ratio of . ( % ci: . - . ) compared with passengers on another bus. there has also been an aircraft outbreak of sars (the coronavirus sars-cov- ) where one symptomatic person generated laboratory-confirmed secondary cases (with other likely cases) ( ) . given this background it is obviously difficult to quantify the risk on sars-cov- transmission on board of a passenger aircraft. therefore, for simulation purposes, we used quantified data from influenza transmission on aircraft. to do this we extracted data from a relevant systematic review and re-analyzed it (see appendix one). this work indicated that an index case might typically generate an average of . secondary cases on a flight of at least three hours duration (assuming no mask use and assuming sars-cov- is similar to influenza in infectivity in such situations). we assumed that cabin crew had the same per person risk of being infected and the same transmission rate as any of the passengers (in the absence of any data on this from the systematic review). we also considered compulsory mask use on flights, as per major airlines in june ( ) . upon arrival in new zealand, we assumed there is entry screening for both passengers and cabin crew. passengers are either placed in supervised quarantined for days (as per actual arrangements in may ) and then released to move freely, or, as an alternative to days of quarantine, we considered various combinations of pcr testing in new zealand. indeed, the pcr test on arrival is already in use in some settings (i.e., austria in may ) with a three hour waiting time until test results. up until their last pcr test, we assumed that people can move freely around new zealand but are required to wear a mask while in the presence of other people; we further assume that half of the cases who develop symptoms during this period will report these symptoms within one day. also, we assumed that if they are tested positive, or if they reported symptoms themselves, contact tracing would identify % of their infected contacts in new zealand who would be isolated after another delay of one day. after entry screening, cabin crew arriving in new zealand are not quarantined but are assumed to stay for one day in new zealand before their next flight (albeit in an scenario analysis they stay in special facilities and do not mix with the public as per some existing processes for new zealand ( )). zealand: secondary cases who are infected by crew members or passengers in new zealand, yet who are not traced, and tertiary cases who are infected by traced secondary cases before they are isolated, have the full length of their infectious period ahead of them. some of them will trigger a major outbreak. to make the simulations as realistic as possible, cabin crew members travel back to australia after their one day layover in new zealand, taking any infection they previously acquired back with them. they are then assumed to have another layover in australia of one day (where uninfected cabin crew members can also pick up the infection from interacting with the public) and may or may not be detected (and removed) at the next boarding screening process. while cabin crew are subjected to exit and entry screening and wear masks onboard, these were the only interventions we considered for them (albeit scenario analysis regarding not having a one day layover in either country). . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint there is as yet insufficient data on this for covid- , so we used an assumed value for influenza (sd = %; . days, erlang distribution). symptomatic period days (split into periods of days each) the who-china joint mission report stated that "the median time from onset to clinical recovery for mild cases is approximately weeks and is - weeks for patients with severe or critical disease" ( ). but given that mild cases may have been missed in this particular assessment, we used a slightly shorter total time period of days (sd = %; . days, erlang distribution). infections that lead to sickness (symptomatic illness) % we used the best estimate from cdc in may of % symptomatic and % asymptomatic ( ). this is more than the % proportion of asymptomatic cases as per a chinese study ( ) , and as used in an australian modelling study ( ) . this value is, however, lower than the % found in an icelandic study ( ) . but it is also higher than that found in another chinese study (at % asymptomatic) ( ) . a uk study of a cohort of health care workers reported that % of all infections were asymptomaticbut this group will be of different ages than the general population ( ) . contagiousness effective reproduction number (re) in the nz postpandemic setting . we considered the best estimate from cdc in may of ro = . ( ) but then reduced this to . to account for behavioral changes in the postpandemic period (i.e., after the first wave in february to april ) in nz. that is such changes as: some persisting voluntary physical distancing such as more working from home, higher levels of online shopping, enhanced hygiene behaviors, and some residual caution around attending large events. relative contagiousness in the prodromal period we used the best estimate from cdc in may of infectiousness of asymptomatic individuals relative to symptomatic individuals of % ( ). contagiousness after the prodromal period % and % in the first five days of symptoms, cases were considered to be fully contagious. in the second five-day period, this was assumed to be at %. the latter figure is still uncertain, but is broadly consistent with one study on changing viral load ( ) . the full details on the control measures we considered are detailed in table . many infected passengers will be asymptomatic (including presymptomatic) at the time of exit screening. e.g. a modelling study of covid- estimated that only % ( %ci: to ) of infected cases would be detected by exit screening ( ) . but this study only considered thermal camera scanning (with a sensitivity of % ( )) and did not consider a symptom questionnaire as well. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . we considered the results of a systematic review and meta-analysis that reported that mask use could result in a large reduction in risk of infection (n= ; adjusted odds ratio = · , %ci: · to · ) ( ) . but we used a slightly higher estimate to better approximate supervised and enforced mask use on the aircraft flight. of note is that many major airlines are now requiring mask use by passengers ( ) and the use of masks on planes by the general public is encouraged by the world health organization ( ) . also of note is the experimental evidence for mask efficacy. for example, one experimental study using avian influenza virus to simulate the pandemic coronavirus, showed that: "n masks, medical masks, and homemade masks made of four layer kitchen paper and one layer cloth could block . %, . %, and . % of the virus in aerosols" respectively ( ) . another experiment has shown how a damp cloth over a speakers mouth reduces emitted droplets detected by laser light scattering by over % ( ) . more specifically another study reported that a non-fitted surgical mask was % effective in blocking detection of seasonal coronavirus (albeit slightly less effective for when measuring viral load in the samples) ( ) . entry screening on arrival in nz (both passengers and cabin crew) % of symptomatic cases identified as per exit screening above (i.e., symptom questionnaire and thermal camera). unless stated otherwise, we always applied entry screening for crew members; for passengers, we only used entry screening if they were not immediately to have a pcr test on arrival or are quarantined anyway. quarantine in nz for passengers only (current practice as per may in nz) we ran the simulations for the -day quarantine period to determine how many passengers were still infectious when quarantine ended. of note is one estimate ( ) that around % of people will still develop symptoms after days (and will also be infectious at this time), but we do not use this estimate in our simulations, because the correct fraction depends on the infection stage of passengers at the beginning of their quarantine. ( ) ). however, we assume here a slightly higher success rate given on-going learnings by the nz health system. see above for details on the likely efficacy of mask use in reducing contagiousness (i.e., from an infected person spreading infection to . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint key value comment passengers up to the time of their final pcr test reduction (as per above) but also no mask use in a scenario analysis others). we also used a higher efficacy than reported in the systematic review ( ) (detailed above), on the basis that this group of passengers would be provided information on the flight and on arrival in nz on the critical importance of mask use and its mandatory nature, along with a free supply of masks on arrival). the proportion of infected passengers who when they develop any symptoms seek medical attention (i.e., they are in the % who will ever develop symptoms) % (selfreporting occurs on average day after symptom onset) we assumed that this proportion is somewhat higher than that for the general community (see below) on the basis that these passengers would be provided information on the flight and on arrival in nz on the critical importance of seeking medical attention if they develop any symptoms. they would also be told that such medical attention would be provided free of charge. we assumed pcr confirmation of selfreported symptoms and if a positive test, then we assumed case isolation and potentially triggering contact tracing. of note is that routinely in nz, . % of people with "fever and cough" symptoms seek medical attention, as reported by the nz flutracking surveillance system ( ) . this is very similar to international estimates for people with influenza who seeking medical attention at % e.g., as used in other modelling ( ) . quarantine of traced contacts day after detection of index cases traced contacts are assumed to b effectively quarantined with no further spread of infection. for the base case of one flight per day from australia and where no interventions were assumed to be in place, we estimated that new zealand would on average experience an outbreak of covid- after . years (table ). this was increased to . years after adding in exit screening upon leaving australia; to . years by adding in mask use on flights; and to . years by adding in entry screening on arrival in new zealand. when adding in pcr testing (accompanied by self-reporting of symptoms, wearing of masks, and contact tracing/case isolation up to the last test), the various scenarios indicated average times to an outbreak of . to . years ( table ). the key driver of these results was not the number of tests but the timing of the last test, as this extended the benefits of mask use, symptom reporting and contact tracing. additional results with the time to last pcr test extended up to day in new zealand (table ), indicate the particularly important benefit from mask use, then symptom self-reporting, and then contact tracing/isolation. the best result was an average outbreak time of . years (table ) . nevertheless, if pcr testing was completely abandoned and replaced with just mask use up to day in new zealand, there was still a reasonable benefit (i.e., . years for "mask use after arrival" in table ). if -days of quarantine was used instead of pcr testing (as per actual practice in may in new zealand), this would be by far the most effective intervention as it increased the average time to an outbreak to over . years for all the scenarios considered. reducing the quarantine from to days resulted in a much more pessimistic result (average waiting time for an outbreak: . years). of note is that all these values are average durations until an outbreak occurs, yet each single flight bears an, albeit small, risk of triggering such an event. outbreaks occur at a random time point (exponentially distributed) with the expected value given in table . as the variance of the exponential distributions is extremely large, the % uncertainty intervals for when such an outbreak occurs are correspondingly very large. that is, in the most pessimistic scenario (no intervention scenario) with an expected duration of . years, % of outbreaks are predicted to occur between . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint . years ( days) and about . years; in the most optimistic scenario (with quarantine) with an expected duration of . years, % of outbreaks occur between . and years. passengers as a group were the major driver of outbreak risk relative to cabin crew: they caused over times as many outbreaks as cabin crew members (depending on the scenario). passengers also caused more outbreaks on a per capita basis than cabin crew, given the : ratio of these groups per flight. table indicates the extreme rarity of outbreaks in new zealand if australia's infection prevalence was times lower than in the base case (i.e., approximating if australia is on the verge of elimination or has eliminated and then experiences a small undetected outbreak from a border control failure). but when scaling up from the base case to ten-fold higher infection prevalence in australia or ten-fold increase in travel volumes from australia to new zealand, then the results scale up accordingly. for both of these together, then there would typically be an outbreak every . years for the current package of interventions, or every . years if the most effective intervention (quarantine) was the key part of the intervention package. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint table : results of the simulations of the base case risk (no interventions) and for multi-layered packages of interventions to prevent covid- outbreaks in new zealand (nz) (assuming the prevalence of infection in australia (au) is . % as per our best estimate for may ). - - - - - - - - - . . - . % - - - - - - - - . . - . % % - - - - - - - . . - . % % % - - - - - - . . - . pcr tests (see table for more details) % million stochastic simulations were run for each intervention strategy. values typically rounded to three meaningful digits. passengers are allowed to move freely in nz from arrival to the last pcr test or after being released from quarantine (see figure ). * a range of days were considered, but the + day option is the one currently adopted for all travelers as per june in nz (albeit combined with quarantine for all travelers to nz). ** prevention of secondary infections due to wearing of masks by potentially infected individual passengers. *** the given fraction of passengers who report having developed symptoms while staying in nz to the health system; they are assumed to be isolated one day after symptom onset and contact tracing may occur after this; traced contacts are pcr tested and isolated after another delay of one day. only pcr test *** , passengers wear masks in nz and self-report symptoms, but no contact-tracing . . australia's infection prevalence is times lower than in the base case (i.e., . %). this could be when australia is on the verge of elimination or has eliminated and then experiences an outbreak after a border control failure [scenario a]. this analysis examined the risk of covid- outbreaks in a covid- -free nation (new zealand), if there was travel from a low-prevalence country (australia) with no control procedures in place, and then if there were various multi-layered interventions in place. it suggested that without any controls there would be such an outbreak of covid- in new zealand after an average of . years (i.e., for just one flight per day from australia and at a very low assumed prevalence of infection in australia at just undetected infected people in a population of million). fortunately, the multi-layered packages of interventions we have modeled can reduce this risk to much lower levels. in particular, quarantine for days was by far the most effective single intervention. nevertheless, the package of pcr testing (with mask use, symptom self-reporting and contact tracing) might be a reasonable alternative, with an expected outbreak occurring after an average of about years. surprisingly, there was also a large benefit from just mask use alone for days by arriving passengers. but specific complexities if quarantine is not used, include the issues of:  might pcr testing on arrival in new zealand provide a false sense of reassurance to passengers if they test negative (and so subsequently impede their mask wearing adherence and self-reporting of symptoms to health workers)?  would the experience of pcr testing on arrival (if the taking of the nasopharyngeal sample is experienced as unpleasant), result in higher levels of defaulting for subsequent pcr testing?  might the requirement to turn up to a health provider for a pcr test on day , be an actual stimulus for improved mask adherence and symptom reporting (relative to intervention packages that did not involve any pcr testing)? . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint  would adherence to mask use by passengers when in the new zealand community be as high as we assume (given the minimal use of masks in the first pandemic wave in nz and lack of government mandates for mass masking)? might the use of fines and threat of deportation improve adherence with mask use amongst passengers once in new zealand?  might digital tools for tracking and even active monitoring of early signs of illness have a role in minimizing risk amongst incoming passengers (especially in the first two to three weeks after arrival? all these issues could benefit from further investigation, potentially involving state-of-the art study designs that remain possible under pandemic conditions ( ) . nevertheless, to select the best multi-layered package of interventions requires information on not only their estimated effectiveness, but also their estimated real-world cost-effectiveness, feasibility, acceptability and adherence with the traveling public, airlines and border control services. obtaining such information would include studying the cost of dealing with false positives of pcr testing and the resources spent chasing up passengers who miss attending their scheduled pcr tests. there is also the need to identify the cost of the new zealand public health system maintaining a state-of-the art contact tracing capacity (though this may be highly desirable for other reasons such as control of measles outbreaks). the relevance of these costs to policy-makers might also be impacted by who is paying. for example, all incoming passengers could be charged a covid- levy and the whole system could be made user-pays and cost-neutral to taxpayers. ultimately, there is also a need for cost-benefit analyses which considers the benefits of increased travel to the new zealand society and economyalong with the risks of outbreaks that need to be rapidly controlled (and might even get completely out of control). with such information policymakers could then decide:  on continuing with the -day quarantine or shifting to pcr testing with mask use interventions.  on the extent to which they open up traveler volumes for different types of traveler from specified low-risk countries (e.g., including essential workers, students, business people, or tourists).  on the extent to which they fund research on evaluating antibody tests to determine if some previously exposed passengers can be exempted some of the quarantine or pcr testing processes (though the quality of such antibody tests is still suboptimal and specificity might be a problem owing to other circulating coronaviruses). this is the first such modeling study (that we know of), to consider interventions to control sars-cov- spread by air travel between two countries. we were also able to consider a wide range of control interventions and to package these in multiple layers of defense and estimate uncertainty intervals. nevertheless, there is quite high uncertainty around some of the parameters we used. for example, the prevalence of infection in australia is highly variable by states/territories, and this is also likely to vary over time. real-world effectiveness of masks on aircraft is still uncertain, along with how well sars-cov- can spread on aircraft. for example, there is some evidence that this pandemic virus is particularly involved in super-spreading events with one estimate being that % of secondary transmissions may have been caused by a small fraction (e.g., ~ %) of infectious individuals ( ) . given all such issues and ongoing improvements in knowledge of the transmission dynamics of sars-cov- , this type of modeling work should be regularly revised and be performed using different types of models. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint appendix one: estimating the risk of sars-cov- in-flight transmission for one index case and with no mask use by cabin crew or passengers we extracted data from the single available systematic review of in-flight outbreaks of influenza ( ) , the majority ( / ) of which were related to the pandemic influenza of . for one outbreak with missing flight duration data, we estimated this using google maps and one study was removed from the dataset as it appeared to be of the same flight as another included study (as noted by the review authors). the results of our analysis are shown in table a . there is of course the limitation here that although pandemic influenza is a respiratory virus like sars-cov- , these two agents might still have different transmission dynamics in the aircraft cabin setting. another issue is that the in-flight influenza outbreaks in the systematic review did suffer from incomplete contact tracing (mean of % traced, median of % traced), and so the true burden of secondary cases is probably somewhat higher for these outbreaks. but countering this is the possibility that there might have been publication bias involved, given that in this review there were only / studies with zero secondary cases. this might suggest that large in-flight outbreaks of influenza were more likely to be studied (and published on) than those with no or little secondary spread. this may somewhat over-estimate the in-flight transmission of influenza, but it may be more appropriate for the transmission of sars-cov- which seems to have a higher reproduction number than influenza. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint * some longer flights included transfers and stopovers (which were treated in the analysis as one flight but we only considering flying time in the calculation of hours, except for one particular stopover where passengers remained on the plane). world health organization. coronavirus disease (covid- ) situation report - new zealand's elimination strategy for the covid- pandemic and what is required to make it work trans-tasman bubble: jacinda ardern gives details of australian cabinet meeting what is the future for travel and migration in age of covid- ? airlines and face masks modelling the potential health impact of the covid- pandemic on a hypothetical european country potential health impacts from the covid- pandemic for new zealand if eradication fails: report to the nz ministry of health when can elimination of sars-cov- 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shenzhen, china: a retrospective cohort study exit strategies: optimising feasible surveillance for detection, elimination and ongoing prevention of covid- community transmission spread of sars-cov- in the icelandic population modes of contact and risk of transmission in covid- among close contacts covid- : pcr screening of asymptomatic healthcare workers at london hospital clinical presentation and virological assessment of hospitalized cases of coronavirus disease in a travel-associated transmission cluster effectiveness of airport screening at detecting travellers infected with novel coronavirus ( -ncov) thermal image scanning for influenza border screening: results of an airport screening study physical distancing, face masks, and eye protection to prevent person-to-person transmission of sars-cov- and covid- : a systematic review and meta-analysis advice on the use of masks in the context of covid- (interim guiance potential utilities of mask-wearing and instant hand hygiene for fighting sars-cov- visualizing speech-generated oral fluid droplets with laser light scattering respiratory virus shedding in exhaled breath and efficacy of face masks the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application variation in false-negative rate of reverse transcriptase polymerase chain reaction-based sars-cov- tests by time since exposure covid- -significant clusters (updated nz participant annual report which interventions work best in a pandemic? estimating the overdispersion in covid- transmission using outbreak sizes outside china this analysis suggests that an outbreak of covid- in new zealand might occur after an average of . years without any interventions and for just one flight per day from australia. this risk is greatly reduced by the currently used -day mandatory quarantine. our analysis shows that there is potential to replace this quarantine period with multi-layered interventions using pcr testing or other controls, including mask use by passengers in new zealand, that would also maintain a low risk of importing the pandemic virus. however, all approaches require continuous careful management and evaluation. the authors have no competing interests. kucirka et al ( ) provide in their figure estimates on the time-course of the fraction of falsenegative pcr results. we have reproduced their curve and translated it into a time-course that gives the test sensitivity for infected individuals, depending on the time since they were exposed to infection. as our simulations are not individual-based, but stochastic representations of a compartmental model, we cannot exactly know the time since exposure for an infected individual who is in a given state of infection (which is represented by one of the latent stages, the prodromal stages, the early and the late infections stages). in order to match these x infection stages, we ran one million stochastic simulations with one infected individual each, recorded the time when this individual entered or left any one of these stages and finally calculated the individual's middle time point (since infection) for each of the x infection stages. in the next step, we recorded the sensitivity values that corresponded to the recorded x simulated time points of the individual, leading to one million simulation-matched values for each of the x infection stages. in a final step, we averaged over these one million values, obtaining x sensitivity values for the infection stages that we used in the simulations. key: cord- - opv t p authors: caraccio, chiara; white, robert s; jotwani, rohan title: no protocol and no liability: a call for covid crisis guidelines that protect vulnerable populations date: - - journal: journal of comparative effectiveness research doi: . /cer- - sha: doc_id: cord_uid: opv t p the covid- pandemic is revealing the unacceptable health disparities across new york city and in this country. the mortality rates of vulnerable and minority populations alone suggest a need to re-evaluate clinical decision making protocols, especially given the recently passed emergency or disaster treatment protection act, which grants healthcare institutions full immunity from liability stemming from resource allocation/triage decisions. here we examine the disparity literature against resource allocation guidelines, contending that these guidelines may propagate allocation of resources along ableist, ageist and racial biases. finally, we make the claim that the state must successfully develop ones that ensure the just treatment of our most vulnerable. the coronavirus disease (covid- ) pandemic has disproportionately affected the most vulnerable populations in new york city and throughout the country. a total of % of those requiring hospitalization have underlying chronic health conditions [ ] . new yorkers over constitute % of covid- hospitalizations in the city, despite comprising only . % of the population [ , ] . the cdc has reported that nationwide, % of hospitalized patients have been african american, despite the fact that only comprising % of the general population; in new york state, african americans constitute % of deaths due to covid- , twice the number of their percentage of the population ( %) [ , ] . low-income communities also suffer disproportionately: new york city zip codes in the bottom % of average incomes constitute % of the city's cases, whereas zip codes in the top % constitute under % of cases [ ] . yet while much of the evidence and commentary around disparity outcomes of covid- addresses the differences in the underlying health status of those most severely affected, there is minimal discussion examining whether resource/triage allocation or liability policies may also be playing a role in exacerbating disparity outcomes [ ] [ ] [ ] [ ] [ ] [ ] . covid- has also shone a bright light on some gaping holes in emergency preparedness systems. particularly, it has brought to light difficulties with insufficient medical supplies and rationing of resources, precipitating the previously unthinkable: how to triage resources in the case of an absolute deficit. the triage policies proposed by states and hospitals around the country have been nonuniform at best [ ] . one common element among these heterogeneous policies is the tendency to further disadvantage the vulnerable populations already affected by covid- (see table for a list of state policies and their distinguishing features). the most widely-commented on form of discrimination has been that of policies that disadvantage the disabled community. a recent study conducted by the association of bioethics program directors (abpd) surveying the ventilator triage protocols of hospitals around the country found that . % of hospital protocols factor resource conservation into their protocol criteria, designating that individuals in need of increased clinical attention and resource-use are a lower priority [ ] . only . % of policies specified that allocation decisions should not be based on disability and some of these policies themselves included decision criteria that would disproportionately disqualify the disabled community [ ] . disability rights new york, an advocacy group for persons with disabilities in new york state, has previously filed a complaint against the new york department of health for its ventilator triage policy, which failed to specify that allocation decisions ought exclude disability. the complaint argues that without explicit instruction urging awareness against implicit bias, hospitals will disproportionately categorize disabled persons as having conditions that disqualify them from ventilator access, even when these conditions do not impact their short-term potential to survive [ ] . advocates have also argued that submitting chronically disabled persons to the same clinical litmus tests for ventilator allocation as healthy persons, such as difficulties at the time of extubation, denies equal access of healthcare facilities to the disabled community [ , ] . less attention has been paid to age-based discrimination. new york's guidelines acknowledge the inequity of factoring age into allocation decisions, but establish a 'tie-breaker' in which children under the age of will be given priority over adults in the case that both would benefit equally from ventilator use [ ] . a total of % of policies assessed in the abpd study utilized age in their criteria [ ] . discrimination against racial minorities may be a feature of any policies that include the presence of comorbidities in their decision criteria. african american patients are three-times more likely to have kidney failure than their white counterparts, nearly twice as likely to suffer congestive heart failure, % more likely to have high blood pressure and less likely to have that blood pressure under control, have higher reported rates of sepsis and are % more likely to have chronic liver disease [ ] [ ] [ ] [ ] [ ] [ ] [ ] . hispanic patients are . -times more likely to have kidney failure than their white counterparts, . -times more likely to suffer congestive heart failure, have higher reported rates of sepsis and are twice as likely to have chronic liver disease [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] . per the abpd study, % of ventilator triage policies utilize the sequential organ failure assessment scores to determine allocation of resources, where higher scores often tend to correlate with worse outcomes and increased baseline comorbidities [ , ] . in light of this, there has been public outcry by physicians that these policies inevitably bias resource allocation away from minority populations with higher likelihood of worse initial assessments that underscores these comorbidities [ ] . low-income populations, who also suffer a higher rate of comorbidities, may also be negatively impacted by these policies compared with their wealthier counterparts [ ] . substantive protocol aside, certain procedural features also need to be examined to ensure just treatment. only . % of hospitals require allocation decisions to be blinded [ ] . on the one hand, granting decision-makers knowledge of the patient's nonclinical characteristics may introduce the possibility of implicit bias playing a role in triage decisions, especially given that biases in medicine have been shown to be exacerbated in high-stress environments [ ] [ ] [ ] [ ] . alternatively, it may be that identity-blind triage criteria do more harm than good; by ignoring the reality that social determinants of health disproportionately disadvantage minority communities, triage criteria that seek to maximize lives saved without correcting for these disadvantages will further deprioritize the lives of the most at-risk groups [ ] . balancing consideration of comorbidities that matter to overall survival with a just and equitable allocation of resources continues to prove difficult for many institutions [ ] . further, the historic difficulty behind successfully incorporating factors such as race into healthcare policy to increase equitable outcomes highlights the acute need for meticulously thought-out policies, developed according to input from physicians and experts well versed in equity issues and from diverse backgrounds [ ] . the protocols mentioned above have been defended on the grounds of providing the greatest public benefit during the pandemic. the new york guidelines, specifically state the aim of these protocols are to "[encourage] allocation practices best suited to maximizing public health" [ ] . undoubtedly, preserving public health during a pandemic is crucial, but protocols that exacerbate disparities based on race, age or disability do not serve the public interest a priori. yet, the appeal to public benefit to justify unjust treatment of the marginalized is not a new concept. historically, charitable hospitals have tried to claim total immunity from civil or criminal liability stemming from malpractice suits by arguing that their charitable trusts were designed to be used to continue treating patients for free, rather than to compensate poor patients who had suffered from negligent treatment (silva v. providence hospital of oakland, england v. hospital of good samaritan, wilmington general hospital v. manlove) [ ] [ ] [ ] . in the landmark case tunkl v. regents of the university of california ( ), the court decided that ucla medical center could not force indigent patients to sign a contract releasing ucla from all malpractice liability in exchange for treatment, establishing that the most vulnerable in our population shall not have their rights denied [ , ] . the majority opinion explains that 'public interest' is not something that can be narrowly defined; in "the integrated. . . society of today, structured upon mutual dependency. . . .prearranged exculpation from [a hospital's] negligence. . . necessarily affects the public interest" [ ] . the same rings truer today than ever: in an interdependent society, prearranged exculpation from harms to our most vulnerable is itself a threat to the public interest. but nearly years after tunkl, similar ethical quandaries have been tied to the covid pandemic. on april , as a part of the - new york state budget, the 'emergency or disaster treatment protection act' (edtpa) was signed into law [ ] . the act grants healthcare workers, including physicians, administrators and hospital managers, immunity from criminal and civil liability for harms and damages resulting from the covid- crisis. immunity will not be granted for acts constituting willful or intentional criminal misconduct, gross negligence, reckless misconduct or intentional infliction of harm. however, edtpa states explicitly that acts, omissions and decisions resulting from resource or staffing shortages will not be considered to fall into any of those aforementioned categories ( § ) [ ] . in other words, the act constructs prearranged exculpation from a hospital's negligence. the immunity granted from the threat of a malpractice suit to healthcare workers and volunteers treating covid- patients with limited resources and at potential risk to their own safety is a widely praised development [ ] [ ] [ ] . however, the breadth of roles granted immunity and the wording of the act raises concerns about the fate of marginalized communities in the case of the covid- situation worsening. past literature that has called for physician immunity during public health emergencies for all but gross negligence and intentional misconduct, as the edtpa does, has still maintained that certain acts, such as extubation of one patient to benefit another, should not be entitled to immunity because they would fall under the gross negligence or the intentional misconduct umbrella [ ] . the edtpa's explicit protection of triage/resource allocation decisions, given the concerning ethical implications of the existing protocols, has major implications for preventing and holding institutions accountable for disparity outcomes. there is an explicit difference between tunkl and related cases and the covid pandemic and this difference is the key to this looming ethical problem: hospitals are not now seeking to disenfranchise their patients, but rather the opposite. during this crisis, healthcare and allied hospital essential workers have shown that they will risk their own lives to help their patients. many of the unorganized and discriminatory policies that hospital triage protocols around the country have exhibited may be a symptom of difficult decision making during an all-encompassing pandemic, not of malintent. according to the abpd study, % of hospitals nationwide have not had time to draft official policy at all; this percentage is likely much higher across all hospitals, since the abpd study only surveyed hospitals with bioethics programs, which may be more likely to have the appropriate infrastructure to create such policies in the first place [ ] . according to the new york guidelines, hospitals have "stressed that they are eager to follow state-level guidance" and have "expressed a preference for state guidance over drafting their own policies" [ ] . the solution, then, is clear: the state must come forward with a protocol that adequately secures the rights of the vulnerable and disseminate it to our hospitals. vulnerable populations deserve just treatment and our healthcare workers deserve the immunity that the edtpa grants them: these two just deserts are only in tension when our policies discriminate against the vulnerable and the state leaves them with no recourse to be compensated for the damages they suffer. unfortunately, the state has not done this. the new york protocols are plagued with issues; in addition to their discriminatory clauses, this protocol has not been updated to reflect decision-making more likely to occur with covid- , such as clinical judgement concerning likelihood of multiorgan failure or predicting length of mechanical ventilatory needs prior to intubation. however, even if this protocol were perfect, the greater issue is that it has been abandoned by state leadership. andrew cuomo declared 'there's no protocol' when asked about triage policy for resource management and a department of health spokesperson, directly contrary to the existence of the guidelines, stated explicitly 'we have no guidelines' when asked [ , ] . the importance of having a standardized framework for triage decisions is not merely a matter of ensuring that each document contains just policies. standardization is in itself a virtue during a crisis: the cdc states that, "making decisions about ventilator distribution and triage using a standard framework for incident management creates a clear hierarchy of accountability and responsibility, facilitates consistent communication and helps minimize differential treatment of patients" [ ] . across medicine the use of standardized protocols has been shown to decrease medical provider implicit bias and has been shown to decrease healthcare disparities [ , ] . crucially, a standardized document would also ensure that each hospital has a robust triage decisions appeals process in place, since the total immunity granted to healthcare workers and institutions by the edtpa renders legal avenues of appeal moot. according to the abpd study, less than % of hospitals have appeals processes in place and only . % specify methods for retrospectively reviewing their own decisions to ensure their policies are being implemented fairly [ ] . in tunkl v. regents of the university of california, the state came down on the side of the vulnerable against the interests of the hospital. thankfully, today there does not need to be any weighing of the rights of marginalized communities against the rights of healthcare workers during this crisis. today we see our healthcare workers risking their lives for their communities; the liability protection that the edtpa grants them is welcome and just. the state must now provide and actively promote a framework that ensures that our physicians can continue providing for every community, especially the marginalized. creating a truly just policy will likely entail working under multidisciplinary collaboration with healthcare workers, bioethicists and other healthcare professionals with the goal of protecting vulnerable and at risk populations. indeed, time is running out. financial & competing interests disclosure who's hit hardest by covid- ? why obesity, stress and race all matter but hospitalization rates for new york city's oldest coronavirus patients went up in the last week age and sex distribution -by county coronavirus is disproportionately killing the black community minorities hit harder by covid- , data shows these graphs show how covid- is ravaging new york city's low-income neighborhoods ventilator triage policies during the covid- pandemic at u.s. hospitals associated with members of the association of bioethics program directors ventilator rationioning -ocr complaint final.pdf the new york times. i will not apologize for my needs new york state department of health. ventilator allocation guidelines ( ). www.health.ny.gov/regulations/task f orce/reports publications/docs/ventilator guidelines.pdf . national kidney foundation. race, ethnicity & kidney disease differences in the incidence of congestive heart failure by ethnicity racial variation in the incidence, care and outcomes of severe sepsis occurrence and outcomes of sepsis: influence of race the epidemiology of sepsis in the united states from through infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis us department of health and human services office of minority health. chronic liver disease and african americans us department of health and human services office of minority health us 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guidelines for ethical allocation of scarce medical resources and services during public health emergencies in michigan for the good of us all: ethically rationing health resources in minnesota in a severe influenza pandemic mississippi department of public health. mississippi pandemic influenza incident annex nevada division of public and behavioral health. nevada crisis standards of care (csc) plan north carolina institute of medicine and north carolina department of health and human services, division of public health. stockpiling solutions: north carolina's ethical guidelines for an influenza pandemic oklahoma state department of public health. emergency preparedness and response service. hospital crisis standards of care oregon department of health pennsylvania department of health and the hospital health system association of pennsylvania. interim pennsylvania crisis standards of care for pandemic guidelines south carolina prepares for pandemic influenza: an ethical perspective tennessee department of health and tennessee hospital association. guidance for the ethical allocation of scarce resources during a community-wide public health emergency as declared by the governor of tennessee north texas mass critical care guidelines document hospital and icu triage guidelines for adults utah hospitals and health systems association for the utah department of health vermont department of health. vermont crisis standards of care plan scarce resource management & crisis standards of care wisconsin hospital association. wisconsin adult ventilator guidelines the authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. this includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.no writing assistance was utilized in the production of this manuscript. key: cord- -kswby it authors: xu, xiao-zhong; liu, qing-po; fan, long-jiang; cui, xiao-feng; zhou, xue-ping title: analysis of synonymous codon usage and evolution of begomoviruses date: - - journal: journal of zhejiang university science b doi: . /jzus.b sha: doc_id: cord_uid: kswby it begomoviruses are single-stranded dna viruses and cause severe diseases in major crop plants worldwide. based on current genome sequence analyses, we found that synonymous codon usage variations in the protein-coding genes of begomoviruses are mainly influenced by mutation bias. base composition analysis suggested that the codon usage bias of av and bv genes is significant and their expressions are high. fourteen codons were determined as translational optimal ones according to the comparison of codon usage patterns between highly and lowly expressed genes. interestingly the codon usages between begomoviruses from the old and the new worlds are apparently different, which supports the idea that the bipartite begomoviruses of the new world might originate from bipartite ones of the old world, whereas the latter evolve from the old world monopartite begomoviruses. synonymous codon usage bias has been investigated in many organisms, as the genetic code is degenerate. the synonymous codons are also non-randomly used in viruses infecting living organisms. several factors such as mutational bias (jenkins and holmes, ; gu et al., ; zhou et al., ) , translational selection (sau et al., a; b; c) , gene function (wang et al., ; gu et al., ; zhou et al., ) , gene length (sau et al., a) , and cpg island (shackelton et al., ) were found to influence codon usage in animal viruses and phages, and mutational bias was found as the major determinant factor. adams and antoniw ( ) also suggested that mutational bias rather than translational selection was the major determinant of codon usage variation amongst plant viruses. geminiviruses (family geminiviridae) are single-stranded dna (ssdna) viruses that cause severe disease in major crop plants worldwide. most geminiviruses belong to the genus begomovirus, which are transmitted exclusively by the whitefly bemisia tabaci (harrison and robinson, ) . many begomoviruses have bipartite genomes known as dna a and dna b. dna a contains the av (coat protein) and av orfs (open reading frames) in the virus strand and, on the complementary strand, four orfs: ac (replication initiation protein), ac (transcriptional activator protein), ac (replication enhancer protein) and ac . the virus and complementary strands of dna b contain two orfs: bv (nuclear shuttle protein) and bc (movement protein). some begomoviruses have a monopartite genome and lack dna b. phylogenetic analysis shows that begomoviruses can be generally divided into two groups, the old world begomoviruses (eastern hemisphere, asia, africa, europe, the mediterranean areas) and the new world begomoviruses (western hemisphere, the americas). all the new world begomoviruses are evolved to bipartite with lack of av orf in dna a, whereas both bipartite and monopartite begomoviruses in the old world encode av orf (harrison and robinson, ) . because of their destructive effect on cash crops (moffat, ; moriones and navas-castillo, ; mansoor et al., ) , numerous studies on begomoviruses have been conducted to understand their symptoms, host range, distribution, genome structure, gene function, and so on zhou et al., ) . in this paper, we report the analysis of codon usage bias in begomoviruses and also perform an evolutionary analysis based on their codon usage pattern. the complete genomic sequences of begomovirus species were downloaded from the genbank database, from which a total of variants of the known protein-coding genes were extracted. to minimize sampling errors, variants were selected for further analysis by the following sifting standard: ( ) the selected genes should be complete coding dna sequences (cds) with correct initial and terminal codons; ( ) only those cds including at least codons were selected in the dataset; ( ) those cds with uncertain annotation or annotated as hypothetical protein-coding genes were excluded from this study. gc content is the frequency of g+c in a coding gene. gc , gc and gc contents are the frequencies of g+c at the first, second and third positions of codons, respectively. a , t , g and c contents are the frequencies of a, t, g and c at the synonymous third position of codons, respectively. effective number of codons (n c ), ranging from to , is generally used to measure the bias of synonymous codons. when n c value approaches , only one codon is used with extreme bias for one amino acid and, if the value is up to , the anonymous codons are used equally with no bias (wright, ) . relative synonymous codon usage (rscu) is defined as the ratio of the observed frequency of codons to the expected frequency given that all the synonymous codons for the same amino acids are used equally. rscu values have no relation to the amino acids usage and the abundance ratio of synonymous codons, which can directly reflect the bias of synonymous codon usage (sharp and li, ) . the codon adaptation index (cai) was used to estimate the extent of bias towards codons that were known to be preferred in highly expressed genes (sharp and li, ) . it is now proved that cai values mostly approach the theoretical values to reflect the expression level of a gene. thus it has been widely utilized to measure the gene expression level (naya et al., ; gupta et al., ) . a cai value ranges from to . , and a higher value indicates a stronger codon usage bias and a higher expression level. codonw version . . (john peden, available at http://sourceforge.net/projects/codonw/), an integrated program, was utilized for calculating gc, gc contents and n c values and then carrying out correspondence analysis (ca), while gc, gc , gc and gc contents were calculated by practical extraction and report language (perl) scripts which were written by us. a , t , g and c contents, as well as rscu and cai values, were also calculated by using perl scripts. ca is the most commonly used multivariate statistical analysis at present (greenacre, ) . this method can successfully present variation trends among genes, and then distribute them along the continuous axis by using rscu value as variable data. in ca, all genes were plotted in a -dimensional hyperspace, according to the usage of the sense codons. major variation trends can be determined using these rscu values and genes ordered according to their positions along the major axis, which can also be used to distinguish the major factors influencing the codon usage of a gene. the set of reference sequences used to calculate cai values in this study were the genes coding for coat proteins. according to the calculated cai values, % of the total genes with extremely high and low cai values were regarded as the high and low dataset, respectively. then we calculated the average rscu values of the two gene samples and subtracted them subsequently in each dataset group (Δrscu). if the Δrscu values are larger than . , then this codon will be defined as the optimal codon (duret and mouchiroud, ) . in order to examine the base composition variation among different genes, the base composition of different protein-coding genes was calculated. table shows that with the exception of the ac gene that has a lower average gc content ( . ), no obvious difference in gc content was found among other tested genes. however, differences in gc content at the different synonymous positions of codons were apparent. for example, gc content at the synonymous first position of codons for the av gene is . , while that for the ac gene is only . . gc content at the synonymous third position of codons for the ac gene is . , while that for the bv gene is only . . it was also observed that the average percentage of gc content was generally higher at the first than at the second codon position (table ) , except for the ac gene whose gc content was larger than gc content. this result suggested that the ac gene might have a special codon usage pattern. in addition we found that av and bv genes had a tendency to usage bias at the synonymous third codon position. the av gene does not tend to use a(t)-ending or g(c)-ending codons but tends to use t-ending codons relative to a-ending codons. however, bv gene apparently uses t-ending codons and seldom used c-ending codons. therefore, av and bv genes should show a stronger codon usage bias among the begomovirus genes. an n c plot (a plot of n c vs gc content) was widely used to investigate the determinants of the codon usage variations among genes in different organisms. it was suggested that if gc content was the only determinant of the codon usage variation among the genes, then the n c value would fall on the continuous curve between n c value and gc content (wright, ). in general, if genes are distributed in n c plots approaching the expected continuous curve with no selection, then codon usage bias of genes is mainly influenced by compositional constraints. otherwise the codon usage bias of genes is more affected by other factors such as translational selection, etc. the n c plot for genes of the begomoviruses showed that although a small number of genes were located on the expected curve, most points lay far below the expected curve ( fig. ) , suggesting that apart from mutation bias, other factors might also play a role in shaping the codon usage bias of begomoviruses (guo et al., ) . table the gc content at the different codon positions and the a, t, g and c contents at the third position of begomovirus genes base composition analysis suggested that the codon usage of the ac gene, which is always embedded in the ac gene, might differentiate from other genes. in addition, strong codon bias was observed in av gene. because of the special characteristics of the abovementioned genes, we selected them for examining the influence factors in shaping the codon usage (fig. a) . the n c plots of av , ac and ac genes suggested that apart from compositional constraints, other factors might play important roles in shaping their codon usage, although high translational selection seems to lay stress on the ac gene because of the wide range of n c values for the same gc content. to examine the reason for n c variation under the same gc content, the relationship between the gc , gc and gc contents for av , ac and ac genes was further examined (fig. b) . it was observed that the gc content was always higher than gc content for the av and ac genes, whereas the gc content of the ac gene was generally lower than the gc content. this result was coincident with the base composition analysis (table ) . thus the variations of the synonymous first and second codon positions for the ac gene might be caused by the translational selection utilizing g or c at the synonymous second position. as the ac gene is always embedded in the ac gene, the codon usage pattern of the ac gene might be influenced by the ac gene. the sequences of ac and ac genes were aligned. it was found that the synonymous third codon position of the ac gene corresponded to the second codon position of the ac gene for all the begomoviruses. thus the base compositional environment of the ac gene might also influence the codon usage pattern of the ac gene. it could be postulated that the second codon position of the ac gene that tended to use g or c should be influenced by compositional constraints other than translational selection. according to the variation analysis of base composition for the genes of begomoviruses, the av gene was selected as a reference dataset to calculate the cai values of all genes. the correlation analysis between cai value and the positions of the genes along the first two major axes (generated by correspondence analysis), as well as other indices, was then calculated. it was observed that the cai values were negatively correlated with the gc and gc contents (r=− . and r=− . respectively, p< . ), while significantly positively correlated with axis (r= . , p< . ). moreover the cai value was also significantly negatively correlated with the n c value, indicating a tendency to a higher cai value or a lower n c value and a higher expression level for begomovirus genes. thus it is feasible to use the av gene as a reference dataset for our estimation of the cai value of begomovirus genes. based on the calculated cai values, % of the total genes with extremely high and low cai values were regarded as the high and the low datasets, respectively. then we compared the codon usage of the high dataset to the low dataset. table shows that codons that code amino acids were apparently used at a high level, and can be determined as translational optimal codons. out of the optimal codons, were ended with g, with c and with t. ca was performed on the rscu value based on the concatenated genes for each begomovirus genome. fig. shows the positions of all tested begomoviruses along the first two major axes. the first major axis accounted for . % of the total variations, while the second major axis accounted for . % of the total variations. in order to detect the codon usage variation of different genomes, the begomoviruses were divided into three groups including the old world begomoviruses with monopartite genomes (om), the old world begomoviruses with bipartite genomes (ob), and the new world begomoviruses with bipartite genomes (nb). the distribution of the three groups along the first two major axes showed that the old world monopartite begomoviruses and the new world bipartite ones were located in two independent fields, indicating that the two groups of begomoviruses exhibit a different codon usage pattern. because the species with a close genetic relationship always present a similar codon usage pattern (sharp et al., ) , the genetic relationship of the two groups of begomoviruses should be far removed from each other. as to the old world begomoviruses with bipartite genomes, we found that the majority of them exhibited a similar codon usage pattern with the old world monopartite begomoviruses, and a few of them showed a similar codon usage to the new world bipartite begomoviruses. an explication of this result might be that a number of old world bipartite begomoviruses evolved to adopt the codon usage pattern of some old world monopartite begomoviruses. moreover, the new world bipartite begomoviruses were closely related to a small number of the old world bipartite ones and far removed from the old world monopartite ones. the results of the n c -plot and base composition analysis indicated that the codon usage pattern of begomoviruses was influenced by mutation bias as well as other factors such as translational selection. comparative analysis of ac and ac genes showed that the compositional environment of the former genes might play a role in dictating the codon usage of the latter gene. thus, although it seems that strong translational selection might have an influence on shaping the codon usage of ac genes, the compositional constraints derived from ac genes might be the major determinant in determining codon usage. consequently it can be speculated that mutation bias might play a major role in shaping the codon usage pattern of begomoviruses. as to the gene itself, the selection pressures from the external environment always act as effective factors in promoting the gene to adapt to the change in the external environment. on the other hand, direct changes to a gene will interfere with or be harmful to the gene. therefore, the base mutation at the synonymous third codon position may not affect the protein expression for ac gene because of the degeneration of genetic codons. but for the embedded ac gene, the corresponding base mutation occurs at the second codon position, which probably results in the loss of function of the translated protein. thus we suggested that ac gene might degenerate step by step during the long period of evolution, which might be an important reason for explaining the loss of function for the ac gene in the bipartite begomoviruses with dna b. the variation analysis of the base composition for begomovirus genes showed that av and bv genes exhibit a stronger codon usage bias and a higher gene expression level. thus cai values of different gene samples were calculated using the av gene as a reference set. the results of correlation analysis indicated the reliability of choosing av gene as a high expression gene sample for begomoviruses. then codons were determined as the major optimal codons for begomoviruses. that will be very important during the design of degenerate primers, the introduction of point mutation, the modification of the virus genes and the investigation of the evolution mechanism of species at the molecule level. it was speculated that monopartite begomoviruses emerged approximately million years ago (rybicki, ; mansoor et al., ) , suggesting that the begomoviruses should have evolved from the original monopartite viruses. rybicki ( ) suggested that the significant expansion of the new world begomoviruses might have occurred after the transmission of the old world begomoviruses to those of the new world by whiteflies. based on codon usage pattern analysis, it could be inferred that there was no direct relationship between the old world monopartite begomoviruses and the new world bipartite ones. interestingly, a small number of the old world bipartite begomoviruses exhibited a similar codon usage pattern to the new world bipartite ones, which suggested that the ancestor of begomoviruses could have evolved from monopartite to bipartite ones before they were transferred to the new world areas. subsequently it was not the old world monopartite begomoviruses but the old world bipartite ones that transmitted to the new world in a certain way and finally evolved into the new world bipartite begomoviruses. in other words, the new world bipartite begomoviruses probably resulted directly from the old world bipartite ones, while the latter evolved from the old world monopartite begomoviruses. it still remains unclear whether the new world begomoviruses directly evolved from the old world bipartite begomoviruses because of the sharp environmental change after their transfer to the new world, or whether the old world bipartite begomoviruses had evolved into the new world bipartite ones before their transmission to the new world. rybicki ( ) suggested that the absence of the av gene in all the new world begomoviruses could be attributed to its earlier loss after the new world begomoviruses arriving in the new world. these results suggest that the current new world begomoviruses evolved from ancient viruses after transferring to the new world. ha et al.( ) speculated that the new identified begomovirus termed corchorus yellow vein virus (coyvv) might belong to a new world begomovirus group that previously existed in the old world, which suggested that the common ancestor of the new world begomovirus might originate from the old world begomovirus. however, both the new world and old world begomoviruses had began to evolve and coexisted in this area for a long time before the separation of the continents. in other words, the present new world begomoviruses might have evolved in the old world, and then moved to the new world by some unknown means (ha et al., ) . codon usage bias amongst plant viruses expression pattern and, surprisingly, gene length shape codon usage in caenorhabditis, drosophila, and arabidopsis revision of taxonomic criteria for species demarcation in the family geminiviridae, and an updated list of begomovirus species theory and applications of correspondence analysis analysis of synonymous codon usage in sars coronavirus and other viruses in the nidovirales evidence of selectively driven codon usage in rice: implications for gc content evolution of gramineae genes synonymous codon usage in lactococcus lactis: mutational bias versus translational selection corchorus yellow vein virus, a new world geminivirus from the old world natural genomic and antigenic variation in whitefly-transmitted geminiviruses (begomoviruses) the extent of codon usage bias in human rna viruses and its evolutionary origin geminivirus disease complexes: the threat is spreading plant pathology: geminiviruses emerges as serious crop threat tomato yellow leaf curl virus, an emerging virus complex causing epidemics worldwide translational selection shapes codon usage in the gc-rich genomes of chlamydomonas reinhardtii a phylogenetic and evolutionary justification for three genera of geminiviridae synonymous codon usage bias in staphylococcus aureus phages: implication in phage therapy comparative analysis of the base composition and codon usages in fourteen mycobacteriophage genomes factors influencing the synonymous codon and amino acid usage bias in at-rich pseudomonas aeruginosa phage phikz evolutionary basis of codon usage and nucleotide composition bias in vertebrate dna viruses an evolutionary perspective on synonymous codon usage in unicellular organisms the codon adaptation index-a measure of directional synonymous codon usage bias, and its potential applications codon usage patterns in escherichia coli, bacillus subtilis, saccharomyces cerevisiae, schizosaccharomyces pombe, drosophila melanogaster and homo sapiens: a review of the considerable within-species diversity. nucleic acids research analysis of codon usage of vaccinia virus genome the 'effective number of codons' used in a gene analysis of synonymous codon usage in h n virus and other influenza a viruses characterization of dnaβ associated with begomoviruses in china and evidence for co-evolution with their cognate viral dna-a key: cord- -wabruzfs authors: gu, wei; deng, xianding; reyes, kevin; hsu, elaine; wang, candace; sotomayor-gonzalez, alicia; federman, scot; bushnell, brian; miller, steve; chiu, charles title: associations of early covid- cases in san francisco with domestic and international travel date: - - journal: clin infect dis doi: . /cid/ciaa sha: doc_id: cord_uid: wabruzfs in early-to-mid march , of ( %) covid- cases at a tertiary care hospital in san francisco, california were travel-related. cases were significantly associated with travel to europe or new york (odds ratio . ). viral genomes recovered from of ( %) cases co-clustered with lineages circulating in europe. m a n u s c r i p t as of april th , , the covid- pandemic, caused by the novel sars-cov- coronavirus , has infected more than . million people worldwide and the rise in cases has been exponential. in particular, new york cases in the united states quickly surged from to > , between march and . by april th there are > , cases in new york and nearby new jersey, threatening to overwhelm hospitals and other regional health care systems in the city. in san francisco, we validated a qrt-pcr test to detect sars-cov- infection from nasopharyngeal swab samples based on the eua (emergency use authorization)approved us cdc assay . during the first days since launch, we performed sars-cov- testing on samples collected from march through march from patients with suspected sars-cov- infection at university of california, san francisco. we reviewed the electronic medical records from the first consecutive sars-cov- positive cases admitted to university of california, san francisco hospitals or seen in outpatient clinics from march through march . data from these covid- patients were matched with randomly selected negative controls who were patients who tested negative for sars-cov- over the same time period. documented history was recorded by a physician or nurse practitioner and included sick contacts, health care worker status, and travel history. among the covid- positive patients, the median age was years, % were female, and % were outpatients (table s ) . we noted that a travel history within weeks of symptom onset (median date mar , ) table s , s ). the association with travel may be due to direct exposure to sars-cov- while in high prevalence regions (e.g. ny) or exposure while traveling (close contact with fellow travelers or airport personnel). one cluster of positive cases associated with covid- infection in an airport worker was categorized as a case of community rather than travel-associated transmission. no significant associations were found with regards to close contacts with known covid- infected persons or frontline healthcare workers. those who did not have a recent travel history, a close contact who was covid- positive, or were not a frontline healthcare worker were categorized as community transmission with an unknown source of infection and comprised % of cases. we conducted viral genomic sequencing and phylogenetic analysis of sars-cov- viruses from of travelers for whom the breadth of coverage of the viral genome was > % - . these viral genomes were aligned using mafft v . with high-coverage viral genomes deposited in the gisaid database , as of march , , in addition to the most recent viral genomes sequenced in california as of may , , for a total of sequences. a maximum likelihood phylogenetic tree was constructed using iqtree (version ) using an hky substitution model ( figure ). we defined genomic clades through the gisaid nomenclature found at that point in time on march , , . the majority ( of ) of all travel cases clustered in the g a c c e p t e d m a n u s c r i p t clade as defined by the spike protein d g variant marker (figure , s , s ), including cases from europe (uc , uc , uc ), cases from new york (uc , uc , uc , uc ), case from los angeles (uc ), and case from chicago (uc ). viruses in the g clade comprise most of the genomes sequenced from patients in europe , , but notably have also been identified in the vast majority of cases associated with the new york sars-cov- outbreak in march to april of , which occurred after the timeline of this study , viruses from two additional travel-associated cases from europe (uc ) and new york (uc ) were mapped to other clades circulating in europe (figure ) . the additional case from europe was found to be part of the v clade, defined by a g v mutation in the ns protein , . limitations of our study include the use of epidemiological data from only the first days of testing at a single institution. nevertheless, in the setting of an emergent pandemic with shifting epidemiology, the results of our study reached statistical significance over categories of travel (all travel, new york, usa, and europe), and yielded data that may have presaged the exponential rise of new york cases and subsequent large-scale outbreak in the new york metropolitan area , . a c c e p t e d m a n u s c r i p t m a n u s c r i p t genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding real-time rt-pcr panel for detection -ncov a genomic survey of sars-cov- reveals multiple introductions into northern california without a predominant lineage metagenomic sequencing with spiked primer enrichment for viral diagnostics and genomic surveillance multiplex pcr method for minion and illumina sequencing of zika and other virus genomes directly from clinical samples mafft: a novel method for rapid multiple sequence alignment based on fast fourier transform disease and diplomacy: gisaid's innovative contribution to global health nextstrain: real-time tracking of pathogen evolution iq-tree: a fast and effective stochastic algorithm for estimating maximum likelihood phylogenies introductions and early spread of sars-cov- in the new york city area sequencing identifies multiple, early introductions of sars-cov to new york city region cryptic transmission of sars-cov- in washington state substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (sars-cov ) epidemiology of covid- in a long-term care facility a c c e p t e d m a n u s c r i p t key: cord- -bxg zqyu authors: bandyopadhyay, g.; meltzer, a. title: let us unite against covid- – a new zealand perspective date: - - journal: irish journal of psychological medicine doi: . /ipm. . sha: doc_id: cord_uid: bxg zqyu novel coronavirus (covid- ) has shaken the existence of mankind worldwide, including that of new zealand. in comparison to other countries, new zealand has had a very low number of confirmed and probable cases as well as covid- -related deaths. new zealand closed its borders and rapidly declared a stringent lockdown to eliminate covid- . the country’s ‘go hard, go early’ policy serves as an exemplar for the rest of the world to date. the mysterious nature of covid- has caused tremendous stress and uncertainty leading to universal conflict between public health and state economy. mental health services and non-government organisations have been proactive in the fight against covid- . though there has been no significant rise in referrals to secondary mental health services to date ( may ), a rapid surge in mental health presentations is widely anticipated. telehealth may prove to be an efficient and cost-effective tool for the provision of future health services. the global pandemic of novel coronavirus has claimed hundreds of thousands of lives and disrupted social, psychological and economic rhythms worldwide. in response to the pandemic, new zealand has closed its borders and declared a stringent lockdown to eliminate the virus. this has resulted in low numbers of confirmed and probable cases as well as covid- -related deaths. new zealand's 'go hard, go early' policy has served as an exemplar for the rest of the world to date (robertson, ) . regardless, the uncertain nature of this highly contagious virus has had significant impact on human emotion, behaviour, cognition and well-being requiring special consideration. health and disability services in new zealand are delivered by a complex network of organisations. approximately one-fifth of the government's spending goes to the health sector. health funding is administered by district health boards that are both purchasers and providers of health services including primary care, hospital, public health and elderly services as well as non-government organisations (ngos) including maori and pacific providers. general practice visits and pharmaceuticals require co-payments but are heavily subsidised. governmentfunded health services are free to new zealanders (ministry of health new zealand, ). the majority of new zealand's population of . million is of european descent ( %), followed by maori ( . %), pacifica ( . %), asian ( %), african ( . %) and other ( %). over a quarter of the new zealand population was born overseas and one-fifth are over years of age (statistics of new zealand, ). maori and elderly populations suffer the greatest health and social disparities (ellison-loschmann et al. ) . thus, these groups face the highest risk for disastrous effects of coronavirus. one in five new zealanders experiences mental health issues every year, and the annual cost of serious mental health is estimated at % of gross domestic expenditure. new zealand has persistently high suicide rates, with youth suicide rates among the worst of the oecd (organisation for economic co-operation and development) countries (he ara oranga, ) . in , the new zealand government introduced the mental health and wellbeing commission bill to the parliament based on the report from the government inquiry into mental health and addiction (he ara oranga, ) . a record . billion nzd was allocated to mental health over a period of years with the aim of integrating mental health services and *address for correspondence: dr gargi bandyopadhyay, whanganui hospital, heads road, whanganui, , new zealand. (email: gargiband@gmail.com) irish journal of psychological medicine, page of . © the author(s), . published by cambridge university press on behalf of the college of psychiatrists of ireland. this is an open access article, distributed under the terms of the creative commons attribution licence (http:// creativecommons.org/licenses/by/ . /), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. doi: . /ipm. . primary care (mental health and wellbeing commission, ) . despite this, it may soon be challenging to provide adequate service to our most vulnerable as a rapid surge of mental health issues is expected in response to covid- . the coronavirus outbreak started in december in wuhan city, china, where cases of mysterious illness including pneumonia of unknown origin were noted. on january , new zealand's government placed entry restrictions on those transiting through or travelling from mainland china requiring a -day period of self-isolation upon return to the country. new zealand's ministry of health set up a team to monitor the situation on january , and risk of viral epidemic was considered low at that time (ministry of health, b). on february , new zealand reported its first case of covid- in an adult male travelling from iran. from march, the -day self-isolation mandate was extended to anyone entering the country with the exception of those travelling from the pacific islands. in an unprecedented turn of events, all borders and entry points were closed to non-residents on march . on march, a four-level covid- alert system was introduced to specify public health and social measures to progressively move the country through phases to prepare, reduce, restrict and lockdown (new zealand government, b). the alert was initially set at level (reduce), but was subsequently raised to level (restrict) on the afternoon of march. a three-month epidemic notice was declared on the same day as a public policy tool to help government agencies to act swiftly and effectively in a rapidly evolving crisis situation (ministry of health new zealand, b). beginning at : pm on march, the alert level was moved to level , putting the country into one of the world's most stringent nationwide lockdowns until : on april . at that time, the nation returned to level for an estimated further weeks (new zealand govt, b). education, business and travel have been severely impacted under alert levels and . to date ( may ), new zealand has had a total of , confirmed and probable cases with zero new cases recorded in the past hours. in total, people have recovered ( %) and only people are in hospital. at the time of writing, the age groups most frequently infected by covid- are - ( %), followed by - ( %), - ( %) and - ( %). sadly, people have lost their lives (statistics new zealand, ). all were over years of age with underlying medical conditions (ministry of health new zealand, a). seventy percent of all new zealand covid- mortalities have been linked to aged care facilities (beynen, ) . despite their vulnerability, those aged years or over account for only % of total cases demonstrating the protective outcomes of new zealand's approach to covid- containment (ministry of health new zealand, a). the mysterious nature of covid- combined with a lack of evidence-based treatment to date has caused tremendous stress, turmoil and uncertainties worldwide. covid- has threatened not only physical health but emotional and cognitive well-being as well. faced with a perceived threat of infection, people begin to regard each other with suspicion and display avoidant behaviours (slovic, ) . the deleterious effect of quarantine including frustration and boredom puts vulnerable people with pre-existing medical conditions, mental illness and advanced age at risk of further psychological morbidity (brooks et al. ) . fear of death, anxiety, panic attacks, adjustment disorders, depression, obsessive compulsive disorder, post-traumatic stress disorder and relapse of pre-existing mental illness are predicted to escalate (chatterjee et al. ) . those with disabilities, developmental disorders and dysfunctional backgrounds face additional risks (brooks et al. ). there has been a % increase in reported domestic violence as victims face increasing difficultly escaping their perpetrators whilst in lockdown (johnston, ) . parents of young children are increasingly stressed as new zealand has announced plans for prolonged online schooling (cluver et al. ) . children with attention deficit hyperactivity disorder, autistic spectrum disorder and other developmental disorders and disabilities appear to be struggling while those with social anxiety seem to thrive in the context of reduced face to face social interaction. regardless, a surge of mental health presentations in children is expected as new zealand exits level lockdown. there is a high level of anxiety amongst health care professionals in regard to limited resources. many doctors hailing from overseas have returned to their countries of origin, causing significant shortages of frontline health care professionals (whanganui dhb, a) . those remaining face concerns around access to personal protective equipment, ventilators and clear cut isolation policies (shanafelt et al. ) . health care workers appear to be at risk of clinical burnout and stigmatisation (brooks et al. ) . new zealand has only just emerged from days of alert level lockdown where all non-essential services were closed. many businesses remain unable to operate under alert level . approximately % of the population faces imminent unemployment (taunton, ) . there are significant concerns about deleterious social and economic consequences. clear and consistent public communication has been essential during periods of psychological turmoil. several initiatives by government and non-government agencies have been launched to support people during the covid- pandemic. well-communicated public education programmes have helped to create a sense of public trust (wallis, ) . despite recent increases in phone calls from distressed patients and families, to date, there has been no significant increase in secondary mental health referrals. as with other medical services, psychiatric inpatient admissions decreased across all age groups during the level lockdown (whanganui, b) . there is concern that patients are delaying medical care due to fears of covid- (brooks et al. ) . post disaster surges in mental health presentations are anticipated in line with historical data (neria et al. ) . mental health professionals aim to continue 'business as usual' primarily by virtual consultation supplemented by face to face assessment where indicated (whanganui, b) . as covid- has emerged in new zealand, health care providers have had to adapt their patient consultation style. telehealth and e-prescribing have rapidly become the new normal, reducing barriers to care (nz telehealth forum and resource centre, ). telehealth, teleconferencing and webinars have emerged as efficient and cost-effective tools in health care services (huesch, ). however, further research is needed regarding long-term telehealth outcomes. new zealanders have championed the art of 'staying together, whilst staying apart'. social media and online platforms have brought together friends and families living miles apart. there has been a surge of good samaritans quietly supporting the frail and elderly during these difficult times. teddy bears peak out from household windows to lift the spirits of our children. despite the restraints of social distancing, new zealanders have remained connected, raised funds and entertained others just to say 'we care'. new zealand has survived many man-made and natural disasters over the years including several volcanic eruptions, the canterbury earthquakes and the hate fuelled shootings in christchurch. just as we did then, we are sure the nation will stay strong and will in fact be strengthened by our collective experience. working together and supporting each other, we will get through this. inside rosewood, the rest home with over half of nz's covid- deaths (www.stuff.co.nz). accessed the psychological impact of quarantine and how to reduce it, rapid review of the evidence impact of covid- pandemic on pre-existing mental health problems covid- information and advice for students improving access to health care among new zealand maori let us unite against report of the government inquiry into mental health and addiction/mental health and addiction inquiry covid coronavirus: domestic violence is the second, silent epidemic amid lockdown our-work/mental-health-and-addictions/governmentinquiry-mental-health-and-addiction/mental-health-andwellbeing-commission) covid- -current cases post traumatic stress disorder following disasters: a systematic review unite against covid- alert system covid- strong govt books support 'go hard ja understanding and addressing sources of anxiety among health care professionals during the covid- pandemic ma perception of risk census totals by topic -national highlights coronavirus: jobs go begging during covid- lockdown covid- coronavirus: new cases in new zealand, no further deaths accessed covid- latest information webpas the authors would like to thank dr joanne stephen-tastard, consultant psychiatrist and medical director, whanganui dhb, for her valuable insights and content recommendations.the authors would also like to thank terry sarten, clinical social worker, whanganui dhb for his editorial contributions. this article received no specific grant from any funding agency, commercial or not-for-profit sectors. the authors have no conflict of interest to disclose. the authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committee on human experimentation with the helsinki declaration of , as revised in . the authors assert that ethical approval was not required for publication of this manuscript. key: cord- -jxlt gby authors: johnson, richard t.; power, christopher title: emerging issues in neurovirology: new viruses, diagnostic tools, and therapeutics date: - - journal: neurologic clinics doi: . /j.ncl. . . sha: doc_id: cord_uid: jxlt gby in the current era of escalating globalization with rapid transport, changing climate, and an ever growing human population with associated changes in lifestyle, poverty, and war, the emergence of new neurologic infections is accelerated. understanding their origins using epidemiologic and molecular tools will contribute to improved control of agent spread throughout vulnerable populations. although few interventions are effective in acute epidemics, the prompt identification of new infectious agents and the roll-out of vaccines together with new antiviral and neuroprotective drugs are promising for the management of future epidemics. in the mid-twentieth century, the discovery of antibiotics, the control of syphilis, the development of poliovirus and measles vaccines, and the anticipation of world eradication of smallpox led many to predict an end of infectious diseases as a serious public health problem. burnet's false prophesy was not alone; robert petersdorf [ ] and others wrote obituaries for the specialty of infectious diseases and left the field. unforeseen was the emergence of new players, that is, new infections to replace and even dwarf the old. in the s and s, this emergence was foreshadowed by the appearance of new recombinant (duck-human) influenza viruses, legionnaires' disease, toxic shock syndrome, lyme disease, and the neurovirulent la crosse strains of california encephalitis virus. the crushing realization that emerging infections could pose an enormous global threat came in the s with the emergence of hiv infections and aids [ ] . over the past decades, significant outbreaks of disease due to ''new'' agents have occurred almost yearly (box ). some have been due to the evolution of more virulent agents (eg, enterovirus , chikunqunya virus, and drug-resistant microbes), some to geographic relocation of agents (eg, dengue type in sri lanka and west nile virus in north america), and some to contact with animals and crossing of species barriers (eg, bovine spongiform encephalopathy, variant creutzfeldt-jakob disease, nipah virus, and the severe acute respiratory syndrome [sars] virus). the majority of these agents have been viruses. added to this threat over the same time has been the growing concern over the weaponization and intentional release of infectious agents, culminating in the anthrax attacks in . millions have died and will die from the spontaneously emerging infections. in the three us terrorist acts, that is, the contamination of salad bars by a religious group in oregon in , the malicious contamination of donuts and muffins probably by a disgruntled worker in a texas laboratory in , and the anthrax mail contamination by an unknown assailant in , only the latter resulted in deaths. the fear of far greater devastation from bioterrorism is real and likely to happen. the spontaneous emergence of new lethal agents is a certainty. several dramatic examples of new outbreaks of viral encephalitis have appeared in the past decade. the three examples summarized herein represent new clinical syndromes due to viruses appearing after evolutionary changes, geographic relocation, and zoonotic infection transmitted to humans. this enteric picornavirus, closely related to coxsackie a , was originally recovered in california in and was associated with handfoot-mouth syndrome, herpangina, occasional cases of viral meningitis, and a single case of fatal encephalitis [ ] . surprisingly, the virus appeared in bulgaria and hungary between and associated with a poliomyelitis-like syndrome, and isolates from these outbreaks caused flaccid paralysis after inoculation into monkeys [ ] . the virus had evolved to simulate poliovirus disease. after another interval, the virus appeared in southeast asia in as the cause of fatal rhomboencephalitis with cardiopulmonary collapse in children under years of age [ , ] . this brainstem localization of clinical findings, imaging studies, and neuropathologic findings indicate a further evolution of neurovirulence to cause a novel and highly lethal illness. west nile virus was originally recovered from the blood of a febrile woman in uganda in [ ] . subsequently, the virus was associated with a dengue-like illness in african children and later with occasional cases of aseptic meningitis in the middle east. ironically, the first documented cases of encephalitis due to west nile virus were in new york city in after patients with advanced cancer were inoculated with the virus on the premise that the ''harmless'' virus might selectively destroy tumor cells. nine patients developed encephalitis, and virus was recovered from the cerebrospinal fluid of three patients [ ] . naturally occurring cases of encephalitis began to appear in the mediterranean basin in the s. a radical change in the epidemiologic pattern was then seen, with large epidemics of encephalitis with high mortality rates. the first epidemics occurred in bucharest in and then in volgograd in . clearly, a more virulent strain of the virus had evolved in this region [ ] . in the summer of , a cluster of patients with encephalitis and severe weakness were reported in the new york borough of queens. they ranged in age from to years, had no common exposure, reported no family illnesses, and spent their evening hours out of doors where investigators found many mosquito larvae in stagnant water. the disease was correctly assumed to be arthropod borne but tentatively diagnosed as st. louis encephalitis. a subsequent virus isolate from a bird dying with encephalitis in the neighboring bronx was identified as west nile virus, and reassessment of the human encephalitis cases showed them to be caused by west nile virus [ ] . sequence analysis of the new york virus showed striking similarity to an isolate from a goose in israel in the previous year [ ] . similar to recent european outbreaks, encephalitis was a common complication, and in % of patients there was flaccid paralysis indicating involvement of anterior horn cells of the spinal cord [ ] . the virus may have been transported by a mosquito aboard an international flight or by a smuggled bird or viremic animal. whatever the courier, the virus found a compatible habitat, successfully over wintered, and spread across the united states and canada over the next years [ ] . the disease took on major public health importance in when it spread coast to coast, causing over human illnesses and deaths. in , cases of disease were recorded in humans; patients had meningitis or encephalitis, with over deaths. in , many had predicted that the virus would not survive the winter or that future summers would present small geographically defined outbreaks similar to those caused by other arthropod-borne viruses in north america. the annual outbreaks and the spread from coast to coast, across canada, and into latin america have occurred, but cases also continue to occur annually in eastern states. the wide range of transmission-competent avian and mosquito species portend a serious future health threat from this neurovirulent strain of west nile virus now firmly established in its new habitat [ ] . in september of , cases of encephalitis were reported among pig farmers and their families in malaysia. initially the disease was thought to be japanese encephalitis, an endemic arthropod-borne disease in the region; however, the new disease affected primarily adults, occurred in household clusters, was associated with contacts with pigs that were ill, and affected some persons who had been immunized against japanese encephalitis virus. each of these factors suggested an alternative cause. in march of , a paramyxovirus named nipah virus was recovered and related to the disease [ ] . an outbreak in a single abattoir in singapore gave insight into the epidemiology of the infection, since only workers transporting or slaughtering pigs became infected. no family member or medical caregiver had evidence of infection, indicating a lack of human-to-human spread [ ] . the slaughter of tens of thousands of pigs in malaysia brought an end to the outbreak, but only after over patients had died. the clinical disease was unique, with multifocal neurologic signs such as cerebellar ataxia, brainstem signs, and segmental myoclonus. imaging studies showed multiple small lesions scattered through the white matter. pathologic studies showed widespread vasculitis with giant cell formation and occlusion of small vessels as well as neuronal infection [ ] . follow-up studies have shown that over % of survivors relapse [ ] . the virus is related to the hendra virus, a paramyxovirus associated with encephalitis in horses and a few handlers in australia. the natural hosts of hendra virus are fruit bats. nipah virus has now been recovered from the saliva and urine of bats, including bats that hung in fruit trees overhanging the pig yards in malaysia [ ] . no further major epidemic has been reported, but scattered small outbreaks of nipah encephalitis have been reported in bengal and bangladesh. these cases have not been related to exposures to sick pigs; therefore, some other modes of transmission from fruit bats to humans occur. the flavivirus hepatitis c virus (hcv) represents one of the leading chronic viral epidemics globally, with over million infected individuals [ ] . in many areas of the world, hcv infection parallels hiv- infection, with injection drug use or blood transfusion being the chief modes of transmission [ ] . like hiv- , hcv is defined by multiple subtypes and immense molecular heterogeneity within subtypes with varying disease severity, largely evident as inflammatory liver disease, which progresses to a cirrhotic state. hcv-infected persons also report neurologic symptomatology, including neurocognitive symptoms (fatigue, mental slowing, poor concentration, forgetfulness, apathy) in the absence of liver disease and exhibit neurologic signs including low-grade encephalopathy (impaired attention and learning, psychomotor slowing) with an overall prevalence of % [ ] and peripheral neuropathy ( %) [ ] with or without cryoglobulinemia. indeed, polymyositis, demyelinating polyneuropathies, and acute demyelinating disseminated encephalomyelitis have also been associated with hcv infection. the underlying pathogenesis of hcv-related disease appears to be largely cellular immune-mediated liver damage in response to chronically infected hepatocytes. multiple studies indicate that leukocytes are chronically infected, together with a persistent viremia. more recently, several studies suggest that hcv-encoded genome (both positive and negative strand rna) and proteins are detectable in the cerebrospinal fluid and brain, often in the setting of hiv- coinfection. both monocytoid (macrophages and microglia) and astrocytes can express selective viral proteins. the extent to which accompanying cellular (and humoral) immunity contributes to neural tissue injury as a bystander cytotoxic effect, or whether virus-encoded proteins are secreted and subsequently injure proximate cells (as proposed for hiv- ) remains uncertain to date. nonetheless, quantitative neuropsychologic studies and neuroimaging including mri and positron emission tomography (pet) disclose abnormalities in hcv-infected patients, which are compounded by hiv- coinfection. although pegylated interferonalpha is an effective therapy for some hcv subtypes, its impact on hcvrelated neurologic disease remains uncertain. as this epidemic grows, the increased risk of neurologic disease requires vigilance and intervention as indicated. the emergence of increasing numbers of new agents appears to be accelerating. this increase may be, in part, an artifact of better surveillance and reporting, but contemporary society has made changes that encourage the evolution of organisms (box ). widespread use and misuse of antibiotics and antiviral drugs has caused natural selection of drug-resistant agents. increased preschooling and nursery care magnifies the spread of enteroviruses. clearing forests for agriculture has led to encounters with new zoonotic agents. the building of dams has created ecological changes that alter the habitats of infectious agents. contemporary animal husbandry with massive feedlots facilitates the spread of agents. even medical advances in the administration of blood products and transplantation have led to the emergence of infections. the two most important factors are the rapidly growing human population and its movement both in speed and volume [ , ] . in , the world population was under billion, and around-the-world travel under sail required over a year for the very few who ventured out. now the world population has burgeoned to over billion. the world can be circumnavigated by air in hours. furthermore, each year, over million persons cross international borders on commercial airplane flights, million work in other countries, and million are refugees or internationally displaced persons [ ] . the population can maintain agents that spread humanto-human, and the speed of travel allows any known infectious agent worldwide to be in a community within one incubation period. the evolution of new agents, the relocation of viruses, and the crossing of species barriers are not new. the measles virus has only one host, humans, but to maintain the virus an interactive population of about , is required; otherwise, the virus disappears as it does on sparsely populated islands. the virus could not have persisted in early neolithic or nomadic cultures. indeed, the typical exanthem of measles was not described by greek and roman physicians but was first recorded by rhazes of baghdad. he dated its arrival in the arab world to the sixth century. contemporary sequence analysis indicates that the measles virus was probably derived from rhinderpest virus of african or asian cattle, suggesting an early zoonotic spread across species barriers. the appearance of measles in france and northern europe has been dated to the eighth century after the moorish invasion. apparently, it was confined below the pyrenees for centuries until an army crossed the mountains, maintaining the virus by soldierto-soldier spread. today, a similar virus could cross this geographic barrier in hours. with the advent of new high-throughput technologies including polymerase chain reaction (pcr) arrays, virus-specific cdna and dna microarrays, and the capacity to perform large-scale dna sequencing [ ] , diagnostic tools for viral infections are rapidly advancing in complexity and in the spectrum of agents that can be detected or newly discovered. indeed, multiple molecular tools have been used over the past decade to characterize west nile virus, the sars coronavirus, and kaposi's sarcoma-associated herpesvirus (hhv- ) [ ] . the recent development of this combined diagnostic approach was particularly rewarding because it led to the discovery of a new human arena virus causing fever and encephalitis. both pcr and oligonucleotide microarray studies were unremarkable, but subsequent high-throughput dna pyrosequencing of patient-derived cdna, together with bioinformatics analyses of protein sequences to exclude human sequences, resulted in the identification of a new neurovirulent arena virus. this metagenomic pyrosequencing approach, albeit, cumbersome at a bioinformatics level, is unbiased in terms of identifying novel sequences and will be invaluable for the discovery and detection of new infectious agents of the nervous system [ ] . in the past years, new protein technologies, including matrix-assisted laser desorption ionization (maldi) and stable isotope labeling with amino acids in cell culture (silac), have also advanced, permitting the detection of new proteins in body fluids including cerebrospinal fluid and the sequencing of individual proteins [ ] . these technologies have immediate value as biomarker detection tools, facilitating the diagnosis of syndromic entities and the evaluation of response to specific treatments. eventually, using nanotechnologies including microfluidic approaches coupled with conventional methods such as antibody detection or pcr, large-scale viral detection will be feasible in the field far from high-technology laboratories, permitting expedited diagnosis and intervention. little can be done to slow the emergence of new microbial threats. the challenge is to anticipate them, detect them early, and respond in effective ways that will contain them (box ). first, surveillance must be global, and international cooperation is crucial. it is easier to contain ebola virus with improved infection control in african hospitals than to counter it at international airports. the sars virus epidemic might have been restricted by quarantines more promptly had information and efforts been shared internationally. new methods of rapid identification and characterization of agents are being developed, but the capacity to perform these studies should be put in place worldwide with major strengthening of public health infrastructure. we cannot prevent the emergence of new microbes and diseases, but we can improve our knowledge of the ecology and molecular biology of these agents. we also can anticipate that every change we make in the environment may impact on the evolution, new encounters, or habitats of these agents. global surveillance and cooperation rapid identification methods characterization to determine origin development and deployment of vaccines and drugs strengthen the public health infrastructure worldwide new therapeutic approaches are rapidly evolving for chronic and acute viral infections. aside from new antiviral drugs that are being developed for a range of viruses such as tenofovir and others, strategies involving the use of therapeutic vaccines, the delivery of monoclonal antibodies, or the use of therapeutically primed dendritic cells represent highly novel approaches. the use of these agents has not yet reached neurovirology; however, other technologies, including the use of nanotechnology-derived liposomes for drug delivery to the brain, are now reality. perhaps the greatest promise lies in the use of small molecules to prevent bystander-mediate injury of the brain. for example, the recent use of minocycline, beta-lactam antibiotics, and free radical scavengers as neuroprotective therapies raises exciting possibilities, albeit, with some caution given the variable outcomes from different studies. in the current era of escalating globalization with rapid transport, changing climate, and an ever growing human population with associated changes in lifestyle, poverty, and war, the emergence of new neurologic infections is highly plausible. understanding their origins using epidemiologic and molecular tools will contribute to improved control of agent spread throughout vulnerable populations. although few interventions are effective in acute epidemics, the prompt identification of new infectious agents and the roll-out of vaccines together with new antiviral and neuroprotective drugs are promising for the management of future epidemics. hiv (worldwide) , lyme borreliosis identified (northeastern united states) , cryptosporidiosis (texas) , bovine spongiform encephalopathy (united kingdom) , multidrug-resistant tuberculosis (prisons in united states and russia) , dengue , subtype iii, virus (sri lanka) , guanarito virus (venezuela) , vibrio cholerae (india) hantavirus pulmonary syndrome (southwestern united states) , variant creutzfeldt-jacob disease largest ebola outbreak (congo) , reversion poliovirus vaccine virus (dominican republic) , influenza virus (hong kong); vancomycin-resistant staphylococcus (united states) , enterovirus fatal rhomboencephalitis (asia); nipah virus encephalitis (malaysia and singapore) , west nile virus encephalitis the doctors' dilemma philadelphia: lippincott-raven publishers an apparently new enterovirus isolated from patients with disease of the central nervous system enterovirus isolated from cases of epidemic poliomyelitis-like disease in bulgaria epidemiologic features of hand-foot-mouth disease and herpangina caused by enterovirus in taiwan neurologic complications in children with enterovirus infection a neurotropic virus isolated from the blood of a native of uganda induced virus infections in man by egypt isolates of west nile virus west nile virus in the us and abroad the outbreak of west nile virus infection in the new york city area in origin of the west nile virus responsible for an outbreak of encephalitis in the northeastern united states poliomyelitis and flaviviruses west nile virus encephalitis in the united states west nile virus neuroinvasive disease fatal encephalitis due to nipah virus among pig farmers in malaysia the neurological manifestations of nipah virus encephalitis, a novel paramyxovirus clinical features of nipah virus encephalitis among pig farmers in malaysia relapsed and late-onset nipah encephalitis nipah virus: a recently emergent deadly paramyxovirus epidemiology of hepatitis c virus infection viral hepatitis in hiv infection prevalence and significance of neurocognitive dysfunction in hepatitis c in the absence of correlated risk factors prevalence and characteristics of peripheral neuropathy in hepatitis c virus population emerging viral infections of the nervous system the soriano award lecture. emerging infections of the nervous system ecological disturbances and emerging infections: travel, dams, shipment of goods, and vectors rebuilding microbial genomes pathogen discovery viral metagenomics systems biology and the host response to viral infection key: cord- -hbd euq authors: søborg, christian; mølbak, kåre; doherty, t. mark; ulleryd, peter; brooks, tim; coenen, claudine; van der zeijst, ben title: vaccines in a hurry date: - - journal: vaccine doi: . /j.vaccine. . . sha: doc_id: cord_uid: hbd euq preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. the development, production and application of emergency vaccinations are the important measures against such threats. vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the spanish flu, the polio epidemics in the s, or the sars outbreak in if its spread had not been contained in time. given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. however, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. in the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in europe by focusing on public–private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies. although progress in medical science has eradicated one infectious disease (smallpox) and threats from other infections such as polio have been reduced by widespread vaccination, new infectious diseases emerge at historically surprisingly high rates-more than one disease per year. there are several explanations. globalisation with its correspondingly increased transport of persons, products and animals can rapidly spread new infectious diseases around the world. furthermore, the condensing of populations with worldwide urbanization and encroachment of humans into new habitats, facilitating close contact with wild animals creates new hazards for transmission of zoonotic infectious agents from animals to man and possibly in the reverse direction, transmitting human pathogens to animals [ , ] . it has been suggested that more than % ( / ) of all new human pathogens in the last century originated from an animal reservoir [ ] . there is an international recognition of the importance of emerging infectious disease in an age of changes, as recently under-lined by the world health organisation: "it would be extremely naïve and complacent to assume that there will not be another disease like aids, another ebola or sars, sooner or later" [ ] . the recent experience with emergence of chikungunya virus in italy underlines these issues. the spread of chikungunya exemplifies how easily a well-known virus from a subtropical region in africa is able to shift vector from one mosquito vector (aedes aegypti) to another (aedes albopictus), disseminate to other climatic zones -including europe -and cause disease in a susceptible population [ ] . the adaptation to a new vector can probably be ascribed to a point mutation in the virus, whereas international travel served as the means of introduction of the virus to the competent vector. a. albopictus have recently become prominent around the mediterranean basin from greece to spain and other arboviral diseases including dengue and west nile virus may use the same vector-possibly causing the next outbreak in europe. climate change may boost this development further by expanding the range of vectors and their capacity to spread disease, together with other activities that transfer potential vectors to new areas. a. albopictus has extended its distribution to europe and the americas as its larvae can be transported in used automobile tyres [ ] . emerging infections have impact not only on the health but also on the economics of the afflicted region. the sars epidemic was estimated to have a direct cost of billion us$ in asia, and the international community was on the verge of a true disaster of even larger dimensions. this blow could have disrupted health care services, and affected societies and economies for years. it was a fortunate coincidence that sars was not transmissible before the onset of the patient's signs and symptoms of disease. hence, the epidemic was contained by traditional measures of disease control such as early case finding, isolation and quarantine. if this had not been the case, the rapid development and use of an emergency vaccine might have been the only feasible measure to prevent further spread. over the last century, vaccines have been shown to be one of the most cost-effective ways to prevent and control diseases. in some situations, such as the re-emergence of smallpox or a new influenza pandemic with a severity comparable to the spanish flu, emergency vaccinations may be the only way to prevent a true disaster for europe and the global society. following the early recognition of a new threat, the current advances in biotechnology, vaccinology (including reverse genetics) and information systems offer us the possibility of developing promising vaccine candidate shortly after the identification of a new infectious agent, under the assumption that this emerging infection is followed by natural immunity. however, additional major bottlenecks for the deployment of emergency vaccines include the lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. in the present discussion paper, we address mechanisms to facilitate development of emergency vaccines in europe by focusing on regulatory aspects and proposing incentives for emergency vaccine production in private vaccine companies. the control of poliomyelitis by rapid development of a vaccine shows that it can be done. it exemplifies what is possible with a strong governmental commitment, public demand and dedication. it also underlines the importance of government institutions taking the lead and responsibility in vaccine development. within only one year -from to -double blinded placebo controlled studies were conducted involving , vaccines and , controls receiving placebo. these trials proved safety and efficacy, leading to licensing of the vaccine shortly after [ ] . the fruit of basic immunology and vaccinology research led to the success of the vaccine and can be condensed into four major discoveries. firstly, characterization of the poliovirus and the definition of three serotypes leading to a trivalent vaccine [ ] . secondly, pathogenicity: the discovery that poliovirus causes paralysis [ ] . thirdly, proof of principle: confirmation that neutralizing antibodies protect against disease [ ] and finally, that virus could be grown in cell cultures for mass vaccine production [ ] . the vaccine campaign was a huge success, and was accepted very well by the population, leading to a steep decrease in polio cases in the years immediately following the vaccine's deployment in europe and usa. today, polio is eradicated in most parts of the world and remains present only in a few of the poorest countries. on the other hand, diseases selected for mass vaccination have to be chosen carefully. the attempt to prevent the spread of swine influenza by vaccination, in usa , is a good example of why to think twice before initiating mass vaccination. influenza specialists were worried that an influenza strain isolated from swine might cross the species barrier and cause a repeat of the spanish flu pandemic from . although no human cases were detected, the decision to start mass vaccination was made and more than million people were vaccinated within a few months. however, suspicion that vaccination was increasing the risk of guillain-barré syndrome as a side effect soon stopped the vaccination campaign [ ] . thus, with a strong public commitment and vital basic knowledge about the pathogen, a successful vaccine can be developed within a short timeframe. however, the decision whether to implement a new vaccine needs to be based on solid risk assessment. potential and unknown hazards associated with the early mass deployment of a new vaccine must be weighed against the risk and nature of the disease. vaccine development -in particular for emergency vaccinesneeds a different business plan than the market-driven approach that underlies the pharmaceutical industry [ ] . private vaccine companies cannot be expected to use resources on improving existing vaccines or developing new vaccine candidates for emerging infectious diseases when there is no current market or if the market is too small or diffuse to be economically feasible. hence, it is important that governments find mechanisms and funding to ensure the fundamentals for the success of a vaccine, namely basic and applied research in public health institutions and academia. furthermore, clear communication is necessary between governments and the vaccine industry on which vaccines need to be developed from a public health perspective. the challenge is to find incentives for the vaccine industry to take part in the development of products that currently do not have a clear market. one solution might be public support to public-private research and development of vaccine candidates in their early preclinical/clinical phases or advance assurances of confirmed purchases of certain volumes of vaccines if they make it to licensure. the european union has promoted the concept of public-private partnerships, but this concept has not resulted in important changes so far [ ] . it is important to find new ways to achieve these aims: it will be too late by the time we suddenly need new vaccines against an emerging epidemic. public-private partnerships in particular are necessary to secure vaccine production from laboratory bench through pilot plant to mass scale industrial production. specific contracts between governments and vaccine companies must be in place to secure that private production capacity is available for emergency vaccination production if needed. as mentioned, modern biotechnology has opened novel approaches for the development of new vaccines allowing production to be carried out in only a few months under the best circumstances (see table ). but obtaining data on clinical efficacy for licensure and regulatory approval will be a major bottleneck for making use of the current technology. without some indication of the immune response required for protection, basic efficacy studies will be difficult. without an animal model, they will be all but impossible. that leaves only the possibility of going to human studies without an indication that the vaccine is effective-a step that is highly unlikely, even in a dire situation. this leads us back to the responsibility of governments and international agencies -including the european union -for laying the groundwork. the first vaccines for sars were developed this way, leveraging preclinical work that had already been done on other coronaviruses [ ] . seasonal influenza vaccines are also made this way; working on the assumption that what has proved efficacious in the past against a related virus will prove efficacious in the future table a toolbox for the rapid development, production and deployment of an emergency vaccine. early recognition of an emerging microbial threat identification and characterization of the causative agent rapid understanding of natural history, pathogenesis, molecular biology and epidemiology; building on work in related pathogens as well as ongoing clinical, laboratory and epidemiological studies identification of potential vaccine candidates identification of potential delivery systems and suitable adjuvant to improve immunogenicity and sparing of antigen and dosages production at pilot plant level development and acceptance of correlates of immunity development and acceptance of correlates of safety limited trials in animals and humans based on these correlates as outcome measures fast-track approval of the vaccines enhancing production capacity by public-private partnerships based on risk assessment and defined objectives: implementation of emergency vaccination post-licensure follow-up of emergency vaccination with data accessible in real-time to medicine-and public health agencies as a surrogate for phase iii trials and ensuring development with advance purchase agreements to establish a market. testing novel vaccine candidates also becomes a bottleneck: just any combination of antigen and delivery system may not be effective. toxicity testing -which is designed to catch only acute problems with a vaccine -can be generally applied to most vaccines. in theory, it may be possible to produce basic safety data even before a complete product is available by testing "mock-up vaccines" in which a placeholder antigen or antigens are used [ ] . this would provide information on the safety of the delivery system including adjuvant, which is generally the most reactogenic part of a vaccine. safety testing of a specific product would still be required, but the reactogenicity of the generic components would already be defined and be one less variable to consider in designing the vaccine. however, efficacy studies require animal models of the infection or the disease and this is both time-and money-intensive. in the absence of a defined animal model, the obvious choice is nonhuman primates, as the closest match to humans, but even if this is possible (i.e. the pathogen will infect primates and produce disease) it may not be practical. both primate and non-primate animal research facilities are in short supply. support of animal facilities is likely to pay dividends when a need arises for rapid assessment of new vaccines. this should be relatively easily put into place, by making it an explicit goal, since it is really only an expansion of existing activities by research supporting agencies. certainly, in the united states, the biodefense initiative has led to a significant expansion in capacity. but it cannot be put into place on an ad hoc basis, nor is it likely that the private sector will become involved-the return on investment in possible emerging diseases is highly uncertain. such facilities take years to establish and their benefits are primarily in research and public health: therefore bodies involved in research and public health will need to take the initiative. once a potential vaccine has been produced and some evidence for efficacy and safety produced in animals through accepted correlates, the same data needs to be reproduced in humans. the current procedures were designed with safety as the foremost consideration and rapidity is not a characteristic of the process: it can take - years (occasionally longer) for a new vaccine to pass through clinical trials. under normal conditions, this is a sensible application of risk/benefit analysis with the emphasis on "first, do no harm". by definition, emerging diseases are not a major health risk-until a significant outbreak occurs. thus, clinical assessment is built around gradual steps-first screening for major risks (phase i, trials generally conducted in very small groups) then subsequently screening for less frequent risks (phase ii, in larger, but still small groups). it is not until phase iii studies, which are often large (thousands to tens of thousands), that efficacy data are expected to be produced. and while phase iii studies are large, they still occasionally fail to uncover rare risks, which only emerge after hundreds of thousands of people have been vaccinated, for example, intussusception of the bowel after administration of rotashield, a vaccine to prevent diarrhoea caused by rotavirus infection [ ] . such events are only uncovered during post-licensure pharmacovigilance. in an epidemic situation, however, the risk/benefit balance changes: if morbidity and mortality due to the pathogen is high, then even a vaccine with significant side effects becomes much more acceptable. it is therefore important to develop procedures for alternative pathways of approval. this should be done in close collaboration with regulatory agencies, and be based on accepted correlates of immunity and safety plus [probably] limited human data. while it will ultimately be up to governments with who guidance under international health regulations to decide what constitutes an "emergency" in which it could be invoked, the bare bones of a "fast-track approval" system for new treatments already exists (influenza mock-up vaccines emea) [ ] , and this procedure could be expanded to accelerate vaccine-testing in clinical trials during a public health emergency. in most cases, the greatest amount of time in a clinical trial is devoted to paperwork, to ensure that the trial complies with regulations designed to minimize risk to participants, ensure transparency and provide a paper trail as a shield against future litigation, should things go awry. in diseases with a poor survival chance -aggressive cancers, for example, or anti-retroviral therapy in the early days of the hiv epidemicregulatory agencies tended to be more forgiving. in such a situation, while safety remains a major issue (particularly for preventive vaccines administered to healthy individuals), testing for efficacy assumes greater importance.the demands for faster processing of vaccines can be addressed by the following steps: . an already-defined regulatory framework within which fasttrack clinical trials can be conducted. this should contain rules for priority review and approval, some (limited) protection against liability to open the process to commercial entities (as they are best equipped for large scale production and distribution) and rules for invoking such a process. they may not (perhaps should not) lead to open-ended approval of a product, being instead intended to allow limited release. . rapid access for vaccine developers to the appropriate regulatory authorities within the emea and authorization for regulators to draw on necessary expertise (perhaps in the form of expert panels) to enable assessments to be made quickly. regulations on relaxing approval (perhaps in the form of approval for a limited time) for import of vaccines not currently approved for use in europe. . a process whereby approval can be granted under the understanding that the complete necessary paperwork can be submitted retrospectively-enabling a rapid progress of efficacy trials, as soon as initial data suggests a vaccine is safe, without waiting for collation, submission and approval before progressing to the paperwork for the next step. . a broader acceptance of surrogate data, e.g., correlates of protection and safety, in the early steps. if (for example) animal toxicity studies raise no concerns, it may be possible to proceed directly to combine phase i/ii studies. this would provide human safety data, but at the cost of placing slightly more participants at risk. the payoff would be earlier access to data indicating whether the vaccine is immunogenic and stimulates the desired type of immune response, plus a more rapid assessment of vaccine safety. acceptance of immunogenicity data as a surrogate for efficacy, based on animal models (and it is here that expert panels will be crucial) might allow rapid release of a product from phase iii trials, subject to the study continuing to collect efficacy data. such an approach could shorten vaccine-testing time by months to years. . finally, while it is possible to enter phase i trials with an experimental product, phase ii has stricter requirements and the product tested needs to be closer to, if not identical with, that which will be taken into phase iii trials-which itself will be the final product. some flexibility on vaccine composition would allow a more rapid progress to phase iii. phase iii trials are intended to demonstrate that a product is efficacious. this is never an easy task and for emerging diseases is complicated by the fact that such diseases are, by definition, not endemic. that means that without reliable surrogate markers, efficacy studies can only be done in endemic countries or selected high-risk populations. it can be expected that even in countries where the disease is endemic, people will be reluctant to accept testing of a vaccine for which safety data and approval has been fast-tracked: some form of compensation mechanism is almost certain to be required to encourage manufacturers and the public to participate in a clinical trial. this passes out of the remit of organizations such as emea and into that of international cooperation, which needs to be arranged at the governmental level. the risks of rapidly proceeding into phase iii can be ameliorated by compromising (to some extent) impartiality. to avoid bias, such large studies are normally blinded and results assessed at the end of the study. however, in a situation where large numbers of people are being vaccinated with a "fast-tracked" vaccine safety concerns will be higher than normal. by putting enhanced surveillance into place and assessing data from cohorts within the main phase iii study, data on adverse events possibly associated with vaccination and efficacy of the vaccine could be collected much faster. objectivity could be maintained by maintaining blinding with regard to the study monitors. this approach essentially expands the role of the data safety management board, whose role is normally to oversee the safety of the study and who do review results on an ongoing basis, to cover decision-making on vaccine efficacy. in such a case, they would need to involve the study designers, which may raise issues of conflict of interest. this can be addressed by again involving expert review panels, but that will almost certainly face resistance from commercial developers who would face exposure of their operating procedures. but where there is an overwhelming public interest in rapid assessment of vaccine efficacy, the conventional rules may need to be relaxed and increased transparency is the safest counter to decreased regulatory oversight. in conclusion, new infectious diseases are emerging at a historically high rate. to secure both public health and economic stability in the future effective countermeasures have to be instituted in advance at governmental levels. implementing fast-track approval systems for emergency vaccines by the regulatory agencies, and underpinning public private partnerships to enable production in the absence of a market would be an important step in order to be prepared for a new pandemic. finally, innovative research towards the understanding of vaccine safety and efficacy and leading to shorter development times should be promoted. american association of physical anthropologists meeting perceived vaccination status in ecotourists and risks of anthropozoonoses surveillance and response to disease emergence a safer future, global health in the century. the annual health report who infectious diseases chikungunya: no longer a third world disease the used tyre trade: a mechanism for the worldwide dispersal of container breeding mosquitoes making history: thomas francis m.d. jr. and the salk poliomyelitis vaccine field trial differentiation of types of poliomyelitis viruses; the grouping of strains into three basic immunological types viremia in human poliomyelitis evaluation of red cross gamma globulin as a prophylactic agent for poliomyelitis iv. final report of results based on clinical diagnoses cultivation of the lansing strain of poliomyelitis virus in cultures of various human embryonic tissues guillain-barre syndrome following vaccination in the national influenza immunization program, united states - why certain vaccines have been delayed or not developed at all european union dg interternal policies of the union a dna vaccine induces sars coronavirus neutralization and protective immunity in mice pandemic vaccines: promises and pitfalls rotavirus vaccines: an overview key: cord- -etw dx i authors: hall, richard j.; wang, jing; peacey, matthew; moore, nicole e.; mcinnes, kate; tompkins, daniel m. title: new alphacoronavirus in mystacina tuberculata bats, new zealand date: - - journal: emerg infect dis doi: . /eid . sha: doc_id: cord_uid: etw dx i because of recent interest in bats as reservoirs of emerging diseases, we investigated the presence of viruses in mystacina tuberculata bats in new zealand. a novel alphacoronavirus sequence was detected in guano from roosts of m. tuberculata bats in pristine indigenous forest on a remote offshore island (codfish island). because of recent interest in bats as reservoirs of emerging diseases, we investigated the presence of viruses in mystacina tuberculata bats in new zealand. a novel alphacoronavirus sequence was detected in guano from roosts of m. tuberculata bats in pristine indigenous forest on a remote offshore island (codfish island). h uman settlement in new zealand is relatively recent compared with that of many countries and extends back ≈ years to when early polynesian explorers first arrived ( ) . a wide variety of exotic flora and fauna have since been introduced, and major changes to the landscape and ecology have occurred, particularly once european settlers arrived years ago. however, large areas of new zealand that are representative of a prehuman state still remain, in particular offshore, islands such as whenua hou (codfish island), which is situated off the southern coast of new zealand. before human settlement, only species of terrestrial mammals were present, all of which were bats. why nonvolant mammals have been absent is unknown, but this absence was probably caused by major extinction events and subsequent geographic isolation that prevented recolonization ( , ) . only bat species remain in new zealand and both are considered vulnerable (www.iucnredlist.org/). the long-tailed bat (chalinolobus tuberculatus) belongs to the family vespertilionidae and is believed to have arrived from australia ≈ million years ago ( ) . the lesser shorttailed bat (mystacina tuberculata) is the sole surviving member of the family mystacinidae in new zealand ( ) . m. tuberculata bats are believed to have diverged from other bat species ≈ million years ago ( ) and have lived in geographic isolation from other bat species until the arrival of c. tuberculatus bats ( ) . m. tuberculata bats also exhibit one of the widest feeding ranges of any bat species and occupy a niche similar to rats and mice because these bats can walk on the ground by using their wings ( ) . little is known about the microorganisms present in these bats. one study found no evidence of pathogenic bacteria or lyssaviruses in them, but reported a sarcocystis sp. ( ) . given the recent intense interest in bats as a reservoir of emerging diseases and the advent of high-throughput sequencing as a virus discovery tool, we investigated the presence of viruses in m. tuberculata bats. four bat guano samples were collected from known roost sites on the remote offshore island of whenua hou (codfish island) ( ° ′s, ° ′e), which is situated at the southern coast of new zealand. this small island is heavily forested and largely unmodified by humans. it has special conservation status for the protection of endangered species, and public access is not permitted ( ) . bat guano was held at °c during transport (< h), resuspended in ml phosphate-buffered saline, and subjected to centrifugation at , × g for min. rna was extracted from µl of supernatant by using the iprep purelink virus kit (life technologies, carlsbad, ca, usa) and eluted into µl reverse transcription pcr molecular-grade water (ambion, austin, tx, usa). metagenomic sequencing was then conducted for of the samples by using an illumina miseq instrument (new zealand genomics ltd., massey genome service, massey university, palmerston north, new zealand) after a series of steps involving dnase i treatment, reverse transcription, multiple displacement amplification (qiagen, valencia, ca, usa), and illumina truseq library preparation (new zealand genomics, ltd.). a total of , , paired-end sequence reads of bp were generated and assembled into contigs by using velvet . . ( ) . assembled contigs were searched for viral sequence by comparison to the nonredundant nucleotide database in genbank (downloaded march ) by using the nucleotide basic local alignment search tool (national center for biotechnology information, bethesda, md, usa). forty-six contigs showed similarity to known genus alphacoronavirus sequences (table) . (raw sequence data are available on request from the authors.) virus sequence from the genus alphacoronavirus was confirmed in all original guano samples by using a specific reverse transcription pcr based on the metagenomic data specific for bp of the rna-dependent rna polymerase (rdrp) gene (genbank accession nos. kf -kf ). the rdrp sequence was identical in all guano samples, and the closest relative was bat coronavirus hku (genbank accession no. dq ; % nt identity, / ). phylogenetic analysis was performed for rdrp ( figure ) and for the spike protein, as derived from metagenomic data (genbank accession no. kf ) (figure ). we propose that these data support identification of a new alphacoronavirus, which has been designated as mystacina bat cov/new zealand/ . the discovery of unknown coronaviruses provides information for a model of coronavirus evolution ( ) and contributes to understanding the process of disease emergence, as in detection of middle east respiratory syndrome coronavirus ( identified in this study from m. tuberculata bat guano is unique in respect to the extreme geographic and evolutionary isolation of the host bat species, which along with c. tuberculatus bats, has been separated from all other mammalian species for ≈ million years. the current estimate for a common ancestor for all coronaviruses is , bce ( ) . to be consistent with this estimate, mystacina bat coronavirus would need to have been introduced to bats on whenua hou within the past years since humans first arrived on this island (given that the island had no other mammals before this time) ( ) or is extant to modern alphacoronavirus phylogenetic radiation (genesis and expansion). apart from humans, only other terrestrial mammals have ever inhabited whenua hou: the brushtail possum (trichosurus vulpecula) and the polynesian rat (rattus exulans), both of which were eliminated from the island in the late s ( ); neither mammal has been reported as a host of alphacoronaviruses. members of the genus alphacoronavirus infect only mammals. thus, an avian origin for this virus is unlikely. an alternative theory of an ancient origin for all coronaviruses has recently been proposed that involves an alternative evolutionary molecular clock analysis, which places the most recent common ancestor many millions of years ago ( ) . the discovery of mystacina bat cov/new zealand/ virus could lend support to such a theory; despite potentially millions of years of isolation, it has diverged relatively little from other extant alphacoronaviruses, as shown by the close relationship of the rdrp and spike protein genes to those of other extant alphacoronaviruses (figures , ). an expanded survey for mystacina bat coronavirus in mammals in new zealand and subsequent characterization of viral genomes would provide further insights into the origin of coronaviruses. no instances of human zoonotic disease from new zealand bat species have been reported. only a small number of conservation staff handle these bats, these staff use standard personal protective equipment and work practice. staff are also offered prophylactic rabies vaccination as a precautionary measure, even though new zealand is free from rabies. the genus alphacoronavirus includes several human and animal pathogens, but on the basis of phylogenetic data in this study, it is not possible to estimate the risk posed by mystacina bat coronavirus to human or animal health. new zealand is not considered a hot spot for emerging infectious diseases. this country is free from many human and animal diseases, such as rabies and foot-and-mouth disease, and infections with human arboviruses because of recent colonization by humans and strict biosecurity border controls ( ) . thus, indigenous wildlife in new zealand has generally been viewed as an almost sterile and unique biosphere. given detection of this coronavirus, more thorough characterization of the ecology of viruses and other microorganisms in native wildlife should be considered to fulfill conservation needs and further safeguard human and domestic animal health against cross-species transmission. when was new zealand first settled? the date debate. te ara-the encyclopedia of evolution of new zealand's terrestrial fauna: a review of molecular evidence miocene mammal reveals a mesozoic ghost lineage on insular new zealand, southwest pacific advances in new zealand mammalogy - : long-tailed bat advances in new zealand mammalogy - : short-tailed bats a time-calibrated species-level phylogeny of bats (chiroptera, mammalia) bats that walk: a new evolutionary hypothesis for the terrestrial behaviour of new zealand's endemic mystacinids infectious and emerging diseases of bats, and health status of bats in new zealand section . codfish island/whenua hou as a place. stewart island/rakiura conservation management strategy and rakiura national park management plan velvet: algorithms for de novo short read assembly using de bruijn graphs an archaeological sequence for codfish island middle east respiratory syndrome coronavirus in bats, saudi arabia discovery of seven novel mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus a case for the ancient origin of coronaviruses emerging infectious diseases in an island ecosystem: the new zealand perspective we thank malcolm rutherford and peter mclelland for collecting samples; thomas briese, ian lipkin, and richard webby for providing guidance and inspiration for this study; new zealand genomics ltd. for providing sequencing services; and new zealand e-science infrastructure for providing highperformance computing resources. key: cord- -ab pz v authors: bogacz, rafal title: estimating the probability of new zealand regions being free from covid- using a stochastic seir model date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: ab pz v this report describes a method for estimating the probability that there are no infected or pre-symptomatic individuals in a populations on a basis of historical data describing the number of cases in consecutive days. the method involves fitting a stochastic version of susceptible exposed infected recovered model, and using the model to calculate the probability that the number of both exposed and infected individuals is equal to . the model is used to predict the current probabilities for all district health boards in new zealand. these probabilities are highly correlated with the number of days with no new cases of covid- . as the number of new cases of covid- declines in new zealand, the government is faced with a decision when to reduce the restrictions and release the country or its parts from lockdown. to assist in such a decision, it may be helpful to know the estimate for a probability of a particular region being free of covid- . this report presents a method for estimating such a probability on the basis of a simple model and presents results for individual district health boards (dhb) in new zealand. a simple model is employed which makes several simplifying assumptions. although these assumptions may not be satisfied, they make the model mathematically tractable, and thus allows estimation of its parameters. in particular, the model makes the following assumptions. • since the ministry of health reports daily numbers of new cases in each dhb, the model treats each dhb as a separate population, thus assuming that individuals do not move between dhb (following government instructions not to travel). • the model assumes that the behaviour of people is the same in the whole new zealand and throughout the analysed period. thus a single set of model parameters is fit to data from march (when the lockdown was introduced in new zealand) to april . • since the number of infected individuals in new zealand is a small fraction of the entire population, the model assumes that the number of susceptible individuals is constant within the analysed period. • the model assumes that infected individuals are eventually identified, and from this time, become fully isolated and no longer infect others. • since the incubation period of covid- is around days [ ] , the individuals who come in contact with the virus first enter a presymptomatic phase lasting on average days to which we refer as an "exposed state", and only then became infectious. given the above assumptions the results of the analysis need to be treated with caution. nevertheless, it us hoped the the presented method may be also refined for more realistic set of assumptions. we considered a stochastic version of susceptible exposed infected recovered (seir) model [ ] . it assumes that each individual can be in one of states, and move between as illustrated in figure a . we denote by e t and i t the number of presymptomatic and infectious people on day t, and by ∆e t and ∆i t the number of people becoming presymptomatic or infectious. we do not have data on these variables, so we assume they are hidden to us and we will infer their values. on the other hand, we denote by ∆r t , the number of people being reported as a new case on day t, and we assume that this observed number corresponds to the amount of people moving to state r where they no longer infect others (as they become fully isolated). thus in the presented model the cases reported correspond to individuals moving to state r rather than i as typically assumed, because we assume that the individuals are more likely to infect others when they are unaware that they have covid- , rather than after diagnosis when they become particularly careful. indeed, james et al. recently wrote that the control measures that specifically target confirmed cases, such as isolation, "could be modelled by a larger reduction in transmission rates for confirmed cases" [ ] . here we for simplicity assume that this transmission rate is reduced to . the changes in model variables over time are given by: the model assumes that every day each infectious individual can infect another person with probability β. hence the number of people becoming presymtomatic is a random variable with a binomial distribution b: . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint additionally, we assume that presymptomatic and infectious people progress to the next state in figure a (i.e. infectious and reported) with probabilities σ and γ respectively: estimating the probability of being virus free we wish to compute a probability distribution of variables e t and i t given data on the number of reported cases upto day t, which we denote by ∆r :t . according to the definition of conditional probability: where to compute p (e t , i t , ∆r :t ) we take advantage of the fact that the dependencies between variables in the model ( figure b ) have a similar structure as in a hidden markov model, so this probability can be computed recursively using an algorithm analogous to the forward algorithm. thus this probability can be decomposed into a sum of probabilities of disjoint events: . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint using the definition of a conditional probability, the probability on the right hand side of the above equation can be written as a chain of conditional probabilities: noting that the variables depend only on subset of variables as illustrated in figure b , the above expression can be simplified to: to compute the term on the right hand side of equation , we note that e t and i t are determined by changes in these variables (equations - ). to find how ∆e t is related with other variables, we can add equations and , and we get: using equations , - we obtain: the above formula allows recursively computing p (e t , i t , ∆r :t ) from the corresponding probability on the previous day. in the presented analyses these probabilities were computed for the values of e t and i t from to n, and in the first step we used uninformative flat prior p (e , i ) = (n+ ) . once the joint probability p (e t , i t , ∆r :t ) is computed for the last available day, we compute the posterior probability from equation , and report the probability of the population being virus free p (e t = , i t = |∆r :t ). to perform the calculation in the previous section, the values of parameters β, σ and γ need to be known. we set σ = . since the average incubation period of covid- is around days. we assume that β and γ are the same for the whole new zealand. to estimate β and γ, . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. we find the values which maximize the product of probabilities of observed data (equation ) across dhb. this maximum is found through a numerical optimization employing a simplex algorithm [ ] with initial values β = γ = . . to assess accuracy of this parameter estimation procedure we tested if the correct values of parameters can be recovered from artificially generated data. we generated artificial datasets, each containing a similar amount of data that is available on the current history of cases in new zealand. for each dataset we randomly generated γ from uniform distribution between . and . , and generated β from uniform distribution between . and γ + . . with these parameters we generated sequences (corresponding to dhb) of ∆r t . for each dhb, the initial numbers of presymptomatic and infectious individuals e and i were generated from uniform distribution between and . the model was then simulated for days according to equations - . for each dataset we estimated β and γ and compared with true values from which data were generated. left and middle displays in figure compare the estimated values of parameters with the true values. there is a significant correlation between true and recovered values (for β: r = . , p < . , for γ: r = . , p < . ). nevertheless there is a bias in the estimation. the direction of this bias is not consistent, but depends on simulation parameters (the recovery presented in figure was done with n = , but for n = the bias is in the opposite direction, not shown). nevertheless the right display in figure shows that the difference between parameters is accurately estimated (r = . , p < . ). it is not surprising that this difference is recovered more accurately, because it determines whether the number of cases increases or decreases over days, which is a salient feature in the data. by contrast, the individual values of β and γ influence less salient features (e.g. a probability of a case after a long period with no cases), so they are more difficult to estimate. we estimated model parameters using the method described in the previous section with parameter n = on the basis of data available at: https://www.health.govt.nz/ourwork/diseases-and-conditions/covid- -novel-coronavirus/covid- -current-situation/covid- - . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint current-cases/. form the available data we extracted the number of cases in each dhb on each day between march and april . subsequently we used the fitted model to predict probability of the population being virus free p (e t = , i t = |∆r :t ). to avoid the influence of the prior probability (that was set arbitrarily) on the estimate, for each dhb model was additionally run on the first week of data times, i.e. the model was estimating the probability on the basis of extended sequence of new cases composed of: [∆r : , ∆r : , ∆r : , ∆r : , ∆r : , ∆r : , ∆r : , ∆r : , ∆r : , ∆r :t ]. due to uncertainty in estimates of individual parameters β and γ seen in figure , we additionally estimated the probabilities of being virus free using a model with β = . and β = . and the parameter γ set on the basis of the estimated difference γ − β. on the basis of data on the number of cases in new zealand in the period from march to april , we estimated parameters of the model as β = . , γ = . . the lower value of a rate with which individuals become infected β than the rate in which cases are reported γ corresponds to the decreasing number of cases over this period. table gives estimated probability that the virus has been eradicated in individual dhbs . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (column pβ). this probability is highly correlated with the number of days with no new cases, also given in table (r = . , p < . ). this relationship is also illustrated in figure . this relationship is not perfect, for example, the estimate for whanganui is % despite only a single day with no cases, because this most recent case was preceded by days with no cases in this dhb. in agreement with occurrence of cases after such long delays, even the regions without cases for or days have the probability estimate around % (rather than %). two most right columns of table also list the probabilities computed with values of β differing form that estimated (and γ set to preserve the difference between estimated γ and β). these probabilities do not differ much, suggesting that the computation of these probabilities is robust to the biases in parameter estimates ( figure ). this report presented a method for estimating the probability of regions being virus free. this probability is highly correlated with the number of days without cases, suggesting that the number of case-free days is a useful quantity to consider while making decisions and informing the public. for example, figure illustrates how this quantity can be visualized. the presented estimates have to be treated with great caution, because the model made many simplifying assumptions which are not satisfied in practice. first, the model assumes that all individuals with covid- are symptomatic and identified, while another model of covid- spread in new zealand assumed probability . of individuals being subclinical [ ] . it has been demonstrated that failing to detect accurately cases of disease increases . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint the time one has to observe no new cases to be sure that a disease has been eradicated [ ] . nevertheless according to the website of the ministry of health (address in the methods), the fraction of cases due to community transmission ( %) is much lower than the number of cases due to the contact with known individual ( %) which suggests that the majority of infectious individuals is being identified in new zealand. second, the model assumed that once individuals become diagnosed, they are isolated, and no longer infect others. this assumption may also be not satisfied in practice. third, the model assumes that there is no movement of individuals between dhb while some of the dhb (e.g. auckland and waitemata) include districts of the same city (e.g. auckland), so the assumptions on travel of individuals between dhb could to be included to refine the model. the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application statistical inference in a stochastic epidemic seir model with control intervention: ebola as a case study suppression and mitigation strategies for control of covid- in new zealand. medrxiv a simplex method for function minimization a stochastic model for covid- spread and the effects of alert level in aotearoa new zealand. medrxiv rigorous surveillance is necessary for high confidence in end-of-outbreak declarations for ebola and other infectious diseases the author thanks medical research council uk for support. key: cord- -tpqsjjet authors: nan title: section ii: poster sessions date: - - journal: j urban health doi: . /jurban/jti sha: doc_id: cord_uid: tpqsjjet nan food and nutrition programs in large urban areas have not traditionally followed a systems approach towards mitigating food related health issues, and instead have relied upon specific issue interventions char deal with downstream indicators of illness and disease. in june of , the san francisco food alliance, a group of city agencies, community based organizations and residents, initiated a collahorarive indicator project called rhe san francisco food and agriculture assessment. in order to attend to root causes of food related illnesses and diseases, the purpose of the assessment is to provide a holistic, systemic view of san francisco\'s food system with a focus on three main areas that have a profound affect on urban public health: food assistance, urban agriculture, and food retailing. using participatory, consensus methods, the san francisco food alliance jointly developed a sec of indicators to assess the state of the local food system and co set benchmarks for future analysis. members collected data from various city and stare departments as well as community based organizations. through the use of geographic information systems software, a series of maps were created to illustrate the assets and limitations within the food system in different neighborhoods and throughout the city as a whole. this participatory assessment process illustrates how to more effectively attend to structural food systems issues in large urban areas by ( t) focusing on prevention rather than crisis management, ( ) emphasizing collaboration to ensure institutional and structural changes, and ( ) aptly translating data into meaningful community driven prevention activities. to ~xplore the strategies to overcome barriers to population sample, we examined the data from three rapid surveys conducted at los angeles county (lac). the surveys were community-based partic· patory surveys utilizing a modified two-stage cluster survey method. the field modifications of the method resulted in better design effect than conventional cluster sample survey (design effect dose to that if the survey was done as simple random sample survey of the same size). the surveys were con· ducte~ among parents of hispanic and african american children in lac. geographic area was selected and d .v ded int.o small c~usters. in the first stage, clusters were selected with probability proportionate to estimated size of children from the census data. these clusters were enumerated to identify and develop a list of households with eligible children from where a random sample was withdrawn. data collectmn for consented respondents involved - minutes in-home interview and abstraction of infor· ma~ion from vaccine record card. the survey staff had implemented community outreach activities designed to fost~r an~ maintain community trust and cooperation. the successful strategies included: developing re.lat on .w. th local community organizations; recruitment of community personnel and pro· vide them with training to conduct the enumeration and interview; teaming the trained community introduction: though much research has been done on the health and social benefits of pet ownership for many groups, there have been no explorations of what pet ownership can mean to adults who are marginalized, living on fixed incomes or on the street in canada. we are a community group of researchers from downtown toronto. made up of front line staff and community members, we believe that community research is important so that our concerns, visions, views and values are presented by us. we also believe that research can and should lead to social change. method: using qualitative and exploratory methods, we have investigated how pet ownership enriched and challenged the lives of homeless and transitionally housed people. our research team photographed and conducted one-on-one interviews with pet owners who have experienced home· lessncss and live on fixed incomes. we had community participation in the research through a partnership with the fred vicror centre camera club. many of the fred victor centre camera club members have experienced homelessness and being marginalized because of poverty. the members of the dub took the photos and assisted in developing the photos. they also participated in the presenta· tion of our project. results: we found that pet ownership brings important health and social benefits to our partici· pants. in one of the most poignant statements, one participant said that pet ownership " ... stops you from being invisible." another commented that "well, he taught me to slow down, cut down the heavy drugs .. " we also found that pet ownership brings challenges that can at times be difficult when one is liv· ing on a fixed income. we found that the most difficult thing for most of the pet owners was finding affordable vet care for their animals. conclusion: as a group, we decided that research should only be done if we try to make some cha.nges about what we have learned. we continue the project through exploring means of affecting social change--for example, ~eti.tions and informing others about the result of our project. we would like to present our ~mdmgs and experience with community-based participatory action resea.rch m an oral. presentarton at yo~r conference in october. our presentation will include com· mumty representation ~f. both front-hne staff and people with lived experience of marginalization and homdessness. if this is not accepted as an oral presentation, we are willing to present the project m poster format. introduction the concept of a healthy city was adopted by the world health organization some time ago and it includes strong support for local involvement in problem solving and implementation of solutions. while aimed at improving social, economic or environmental conditions in a given community, more significantly the process is considered to be a building block for poliq reform and larger scale 'hange, i.e. "acting locally while thinking globally." neighbourhood planning can he the entry point for citizens to hegin engaging with neighbours on issues of the greater common good. methods: this presentation will outline how two community driven projects have unfolded to address air pollution. the first was an uphill push to create bike lanes where car lanes previously existed and the second is an ongoing, multi-sectoral round table focused on pollution and planning. both dt•monstrate the importance of having support with the process and a health focus. borrowing from traditions of "technical aid"• and community development the health promoter /planner has incorporated a range of "determinants of health" into neighbourhood planning discussions. as in most urban conditions the physical environment is linked to a range of health stressors such as social isolation, crowding, noise, lack of open space /recreation, mobility and safety. however typical planning processes do not hring in a health perspective. health as a focus for neighbourhood planning is a powerful starti_ng point when discussing transportation planning or changing land-uses. by raising awareness on determmants of health, citizens can begin to better understand how to engage in a process and affect change. often local level politics are involved and citizens witness policy change in action. the environmental liaison committee and the dundas east hike lanes project resulted from local level initiatives aimed at finding solutions to air pollution -a priority identified hy the community. srchc supported the process with facilitation and technical aid. _the processs had tangible results that ultimately improve living conditions and health. •tn the united kmgdom plannm in the 's established "technical aid" offices much like our present day legal aid system to provide professional support and advocacy for communities undergoing change. p - (c) integrating community based research: the experience of street health, a community service agency i.aura cowan and jacqueline wood street health began offering services to homeless men and women in east downtown ~oronto in . nursing stations at drop-in centres and shelters were fo~lowed by hiv/aids prevent ~, harm reduction and mental health outreach, hepatitis c support, sleeping bag exchange, and personal tdennfication replacement and storage programs. as street health's progi;ams expanded, so to~ did the agency:s recognition that more nee~ed t~ be done to. address the underl~ing causes of, th~ soct~l and economic exclusion experienced by its clients. knowing t.h~t. a~voca~y ts. helped by . evtd~nce , street he.alt~ embarked on a community-based research (cbr) initiative to dent fy commumty-dnven research priorities within the homeless and underhoused population. methods: five focus groups were conducted with homeless people, asking participants to identify positive and negative forces in their lives, and which topics were important to take action on and learn more about. findings were validated through a validation meeting with participants. results: participants identified several important positive and negative forces in their lives. key positive forces included caring and respectful service delivery, hopefulness and peer networks. key negative forces included lack of access to adequate housing and income security, poor service delivery and negative perceptions of homeless people. five topics for future research emerged from the process, focusing on funding to address homelessness and housing; use of community services for homeless people; the daily survival needs of homeless people and barriers to transitioning out of homelessness; new approaches to service delivery that foster empowerment; and policy makers' understanding of poverty and homelessness. conclusions: although participants expressed numerous issues and provided much valuable insight, definitive research ideas and action areas were not clearly identified by participants. however, engagement in a cbr process led to some important lessons and benefits for street health. we learned that the community involvement of homeless people and front-line staff is critical to ensuring relevance and validity for a research project; that existing strong relationships with community parmers are essential to the successful implementation of a project involving marginalized groups; and that an action approach focusing on positive change can make research relevant to directly affected people and community agency staff. street health benefited from using a cbr approach, as the research process facilitated capacity building among staff and within the organization as a whole. p - (c) a collaborative process to achieve access to primary health care for black women and women of colour: a model of community based participartory research notisha massaquoi, charmaine williams, amoaba gooden, and tulika agerwal in the current healthcare environment, a significant number of black women and women of color face barriers to accessing effective, high quality services. research has identified several issues that contribute to decreased access to primary health care for this population however racism has emerged as an overarching determinant of health and healthcare access. this is further amplified by simultaneous membership in multiple groups that experience discrimination and barriers to healthcare for example those affected by sexism, homelessness, poverty, homophobia and heterosexism, disability and hiv infection. the collaborative process to achieve access to primary health care for black women and women of colour project was developed with the university of toronto faculty of social work and five community partners using a collaborative methodology to address a pressing need within the community ro increase access to primary health care for black women and women of colour. women's health in women's hands community health centre, sistering, parkdale community health centre, rexdale community health centre and planed parenthood of toronto developed this community-based participatory-action research project to collaboratively barriers affecting these women, and to develop a model of care that will increase their access to health services. this framework was developed using a process which ensured that community members from the target population and service providers working in multiculrural clinical settings, were a part of the research process. they were given the opportunity to shape the course of action, from the design of the project to the evaluation and dissemination phase. empowerment is a goal of the participatory action process, therefore, the research process has deliberately prioritized _ro enabling women to increase control over their health and well-being. in this session, the presenters will explore community-based participatory research and how such a model can be useful for understanding and contextualizing the experiences of black women and women of colour. they will address. the development and use of community parmerships, design and implementation of the research prorect, challenges encountered, lessons learnt and action outcomes. they will examine how the results from a collaborative community-based research project can be used as an action strategy to poster sessions v address che social determinants of women health. finally the session will provide tools for service providers and researchers to explore ways to increase partnerships and to integrate strategies to meet the needs of che target population who face multiple barriers to accessing services. lynn scruby and rachel rapaport beck the purpose of this project was ro bring traditionally disenfranchised winnipeg and surrounding area women into decision-making roles. the researchers have built upon the relationships and information gachered from a pilot project and enhanced the role of input from participants on their policy prioriries. the project is guided by an advisory committee consisting of program providers and community representatives, as well as the researchers. participants included program users at four family resource cencres, two in winnipeg and two located rurally, where they participated in focus groups. the participants answered a series of questions relating to their contact with government services and then provided inpuc as to their perceptions for needed changes within government policy. following data analysis, the researchers will return to the four centres to share the information and continue che discussion on methods for advocating for change. recommendations for program planning and policy development and implementation will be discussed and have relevance to all participants in the research program. women's health vera lefranc, louise hara, denise darrell, sonya boyce, and colleen reid women's experiences with paid and unpaid work, and with the formal and informal economies, have shifted over the last years. in british columbia, women's employability is affected by government legislation, federal and provincial policy changes, and local practices. two years ago we formed the coalition ior women's economic advancement to explore ways of dealing with women's worsening economic situations. since the formation of the coalition we have discussed the need for research into women's employabilicy and how women were coping and surviving. we also identified how the need to document the nature of women's employability and reliance on the informal economy bore significanc mechodological and ethical challenges. inherent in our approach is a social model of women's health that recognizes health as containing social, economic, and environmental determinants. we aim to examine the social contexc of women's healch by exploring and legitimizing women's own experiences, challenging medical dominance in understandings of health, and explaining women's health in terms of their subordination and marginalizacion. through using a feminist action research (far) methodology we will explore the relationship between women's employability and health in communities that represent bricish columbia's social, economic, cultural/ethnic, and geographic diversities: skidegate, fort st . .john, lumhy, and surrey. over the course of our year project, in each community we will establish and work with advisory committees, hire and train local researchers, conduct far (including a range of qualitative methods), and support action and advocacy. since the selected communities are diverse, the ways that the research unfolds will ·ary between communities. expected outcomes, such as the provision of a written report and resources, the establishment of a website for networking among the communities, and a video do.:umentary, are aimed at supporting the research participants, coalition members, and advisory conuniuces in their action efforts. p t (c) health & housing: assessing the impact of transitional housing for people living with hiv i aids currently, there is a dearth of available literature which examines supporrive housing for phas in the canadian context. using qualitative, one-on-one interviews we investigace the impact of transitional housing for phaswho have lived in the up to nine month long hastings program. our post<'r pr<·senta-t on will highlight research findings, as well as an examination of transitional housing and th<· imp;kt it has on the everyday lives of phas in canada. this research is one of two ground breaking undertakings within the province of ontario in which fife house is involved. p - (c) eating our way to justice: widening grassroots approaches to food security, the stop community food centre as a working model charles l.evkoe food hanks in north america have come co play a central role as the widespread response to growing rates of hunger. originally thought to be a short term-solution, over the last years, they have v poster sessions be · · · · d wi'thi'n society by filling the gaps in the social safety net while relieving govemcome mst tut ona ze . . . t f the ir responsibilities. dependent on corporate donations and sngmauzmg to users, food banks men so th' . · i i . are incapable of addressing the structural cause~ of ~u~ger. s pres~ntation w e~~ ore a ternanve approaches to addressing urban food security while bmldmg more sustamabl.e c~mmumt es. i:nrough the f t h st p community food centre, a toronto-based grassroots orgamzanon, a model is presented case e h'l k' b 'id · b that both responds to the emergency food needs of communities w e wor mg to. u ~ sustama le and just food system. termed, the community food centre model. (cfc), ~he s~op is worki?g to widen its approach to issues of food insecurity by combining respectful ~ rect service wit~ com~~mty ~evelop ment, social justice and environmental sustainability. through this approach, various critical discourses around hunger converge with different strategic and varied implications for a~ion. as a plac~-based organization, the stop is rooted within a geographical space and connected directly to a neighbourhood. through working to increase access to healthy food, it is active in maintaining people's dignity, building a strong and democratic community and educating for social change. connected to coalitions and alliances, the stop is also active in organizing across scales in connection with the global food justice movement. inner city shelter vicky stergiopoulos, carolyn dewa, katherine rouleau, shawn yoder, and lorne tugg introduction: in the city of toronto there are more than , hostel users each year, many with mental health and addiction issues. although shelters have responded in various ways to the health needs of their clients, evidence on the effectiveness of programs delivering mental health services to the home· less in canada has been scant. the objective of this community based research was to provide a forma· tive evaluation of a multi-agency collaborative care team providing comprehensive care for high needs clients at toronto's largest shelter for homeless men. methods: a logic model provided the framework for analysis. a chart review of clients referred over a nine month period was completed. demographic data were collected, and process and outcome indicators were identified for which data was obtained and analyzed. the two main outcome measures were mental status and housing status months after referral to the program. improvement or lack of improvement in mental status was established by chart review and team consensus. housing outcomes were determined by chart review and the hostel databases. results: of the clients referred % were single and % were unemployed. forty four percent had a psychiatric hospitalization within the previous two years. the prevalence of severe and persistent men· tal illness, alcohol and substance use disorders were %, % and % respectively. six months after referral to the program % of clients had improved mental status and % were housed. logistic regression controlling for the number of general practitioner and psychiatrist visits, presence of person· ality or substance use disorder and treatment non adherence identified two variables significantly associ· ated mental status improvement: the number of psychiatric visits (or, . ; % ci, . - . ) and treatment non adherence (or, . ; % ci, . - . ). the same two variables were associated with housing outcomes. history of forensic involvement, the presence of a personality or substance use disorder and the number of visits with a family physician were not significantly associated with either outcome. conclusions: despite the limitations in sample sire and study design, this study can yield useful informa· tion to program planners. our results suggest that strategies to improve treatment adherence and access to mental health specialists can improve outcomes for this population. although within primary care teams the appropriate collaborative care model for this population remains to be established, access to psychiatric follow up, in addition to psychiatric assessment services, may be an important component of a successful program. mount sinai hospital (msh) has become one of the pre-eminent hospitals in the world by contributing to the development of innovative approaches to effective health care and disease prevention. recently, the hospital has dedicated resources towards the development of a strategy aimed at enhancing the hospital's integration with its community partners. this approach will better serve the hospital in the current health care environment where local health integration networks have been struck to enhance and support local capacity to plan, coordinate and integrate service delivery. msh has had early success with developing partnerships. these alliances have been linked to programs serving key target populations with _estabhshe~. points of access to msh. recognizing the need to build upon these achievements to remain compe~mve, the hospital has developed a community integration strategy. at the forefront of this strategy is c.a.r.e (community advisory reference engine): the hospital's compendium of poster sessions v community partners. as a single point of access to community partner information, c.a.r.e. is more than a database. c.a.r.e. serves as the foundation for community-focused forecasting and a vehicle for inter and intra-organizational knowledge transfer. information gleaned from the catalog of community parmers can be used to prepare strategic, long-term partnership plans aimed at ensuring that a comprehensive array of services can be provided to the hospital community. c.a.r.e. also houses a permanent record of the hospital's alliances. this prevents administrative duplication and facilitates the formation of new alliances that best serve both the patient and the hospital. c.a.r.e. is not a stand-alone tool and is most powerful when combined with other aspects of the hospital's community integration strategy. it iscxpected that data from the hospital's community advisory committees and performance measurement department will also be stored alongside stakeholder details. this information can then be used to drive discussions at senior management and the board, ensuring congruence between stakeholder, patient and hospital objectives. the patient stands to benefit from this strategy. the unique, distinct point of reference to a wide array of community services provides case managers and discharge planners with the information they need to connect patients with appropriate community services. creating these linkages enhances the patient's capacity to convalesce in their homes or places of residence and fosters long-term connections to neighborhood supports. these connections can be used to assist with identifying patients' ongoing health care needs and potentially prevent readmission to hospital. introduction: recruiting high-risk drug users and sex workers for hiv-prevention research has often been hampered by limited access to hard to reach, socially stigmatized individuals. our recruitment effom have deployed ethnographic methodology to identify and target risk pockets. in particular, ethnographers have modeled their research on a street-outreach model, walking around with hiv-prevention materials and engaging in informal and structured conversations with local residents, and service providers, as well as self-identified drug users and sex workers. while such a methodology identifies people who feel comfortable engaging with outreach workers, it risks missing key connections with those who occupy the margins of even this marginal culture. methods: ethnographers formed a women's laundry group at a laundromat that had a central role as community switchboard and had previously functioned as a party location for the target population. the new manager helped the ethnographers invite women at high risk for hiv back into the space, this time as customers. during weekly laundry sessions, women initiated discussions about hiv-prevention, sexual health, and eventually, the vaccine research for which the center would be recruiting women. ra.its: the benefits of the group included reintroducing women to a familiar locale, this time as customers rather than unwelcome intruders; creating a span of time (wash and dry) to discuss issues important to me women and to gather data for future recruitment efforts; creating a location to meet women encountered during more traditional outreach research; establishing the site as a place for potential retention efforts; and supporting a local business. women who participated in the group completed a necessary household task while learning information that they could then bring back to the community, empowering them to be experts on hiv-prevention and vaccine research. some of these women now assist recruitment efforts. the challenges included keeping the group women-only, especially after lunch was provided, keeping the membership of the group focused on women at risk for hiv, and keeping the women in the group while they did their laundry. conclusion: public health educators and researchers can benefit from identifying alternate congregation sites within risk pockets to provide a comfortable space to discuss hiv prevention issues with high-risk community members. in our presentation, we will describe the context necessary for similar research, document the method's pitfalls and successes, and argue that the laundry group constitutes an ethical, respectful, community-based method for recruitment in an hiv-prevention vaccine trial. p - t (c) upgrading inner city infrastructure and services for improved environmental hygiene and health: a case of mirzapur in u.p. india madhusree mazumdar in urgency for agricultural and industrial progress to promote economic d.evelopment follo_wing independence, the government of india had neglected health promotion and given less emphasis on infrastructure to promote public health for enhanced human pro uct v_ity. ong wit r~p m astrucrure development, which has become essential if citie~ are to. act ~s harbmger.s of econ~nuc ~owth, especially after the adoption of the economic liberalization policy, importance _is a_lso ~emg g ve.n to foster environmental hygiene for preventive healthcare. the world health orga~ sat ~ is also trj:' ! g to help the government to build a lobby at the local level for the purpose by off~rmg to mrroduce_ its heal.thy city concept to improve public health conditions, so as to reduce th_e disease burden. this pape~ s a report of the efforts being made towards such a goal: the paper descr~bes ~ c~se study ?f ~ small city of india called mirzapur, located on the banks of the nver ganga, a ma or lifeline of india, m the eastern part of the state of uttar pradesh, where action for improvement began by building better sanitation and environmental infrastructure as per the ganga action plan, but continued with an effort to promote pre· ventive healthcare for overall social development through community participation in and around the city. asthma physician visits in toronto, canada tara burra, rahim moineddin, mohammad agha, and richard glazier introduction: air pollution and socio-economic status are both known to be associated with asthma in concentrated urban settings but little is known about the relationship between these factors. this study investigates socio-economic variation in ambulatory physician consultations for asthma and assesses possible effect modification of socio-economic status on the association between physician visits and ambient air pollution levels for children aged to and adults aged to in toronto, canada between and . methods: generalized additive models were used to estimate the adjusted relative risk of asthma physician visits associated with an interquartile range increase in sulphur dioxide, nitrogen dioxide, pm . , and ozone, respectively. results: a consistent socio-economic gradient in the number of physician visits was observed among children and adults and both sexes. positive associations between ambient concentrations of sul· phur dioxide, nitrogen dioxide and pm . and physician visits were observed across age and sex strata, whereas the associations with ozone were negative. the relative risk estimates for the low socio-«onomic group were not significantly greater than those for the high socio-economic group. conclusions: these findings suggest that increased ambulatory physician visits represent another component of the public health impact of exposure to urban air pollution. further, these results did not identify an age, sex, or socio-economic subgroup in which the association between physician visits and air pollution was significantly stronger than in any other population subgroup. eco-life-center (ela) in albania supports a holistic approach to justice, recognizing the environ· mental justice, social justice and economic justice depend upon and support each other. low income cit· izens and minorities suffer disproportionately from environmental hazards in the workplace, at home, and in their communities. inadequate laws, lax enforcement of existing environmental regulations, and ~ea.k penalties for infractions undermine environmental protection. in the last decade, the environmental ust ce m~ve~ent in tirana metropolis has provided a framework for identifying and exposing the links ~tween irrational development practices, disproportionate siting of toxic facilities, economic depres· s on, and a diminished quality of life in low-income communities and communities of color. the envi· ~onmental justice agenda has always been rooted in economic, racial, and social justice. tirana and the issues su.rroun~ing brow~fields redevelopment are crucial points of advocacy and activism for creating ~ubstantia~ social chan~~ m low-income communities and communities of color. we engaging intensively m prevcnnng co'.' mumnes, especially low income or minority communities, from being coerced by gov· ernmenta~ age_nc es or companies into siting hazardous materials, or accepting environmentally hazard· ous_ practices m order to create jobs. although environmental regulations do now exist to address the environmental, health, and social impacts of undesirable land uses, these regulations are difficult to poster sessions v enforce because many of these sites have been toxic-ridden for many years and investigation and cleanup of these sites can be expensive. removing health risks must be the main priority of all brown fields action plans. environmental health hazards are disproportionately concentrated in low-income communities of color. policy requirements and enforcement mechanisms to safeguard environmental health should be strengthened for all brownfields projects located in these communities. if sites are potentially endangering the health of the community, all efforts should be made for site remediation to be carried out to the highest cleanup standards possible towards the removal of this risk. the assurance of the health of the community should take precedence over any other benefits, economic or otherwise, expected to result from brownfields redevelopment. it's important to require from companies to observe a "good neighbor" policy that includes on-site visitations by a community watchdog committee, and the appointment of a neighborhood environmentalist to their board of directors in accordance with the environmental principles. vancouver - michael buzzelli, jason su, and nhu le this is the second paper of research programme concerned with the geographical patterning of environmental and population health at the urban neighbourhood scale. based on the vancouver metropolitan region, the aim is to better understand the role of neighbourhoods as epidemiological spaces where environmental and social characteristics combine as health processes and outcomes at the community and individual levels. this paper builds a cohort of commensurate neighbourhoods across all six censuses periods from to , assembles neighbourhood air pollution data (several criterion/health effects pollutants), and providing an analysis to demonstrate how air pollution systematically and consistently maps onto neighbourhood socioeconomic markers, in this case low education and lone-parent families. we conclude with a discussion of how the neighbourhood cohort can be further developed to address emergent priorities in the population and environmental health literatures, namely the need for temporally matched data, a lifecourse approach, and analyses that control for spatial scale effects. solid waste management and environment in mumbai (india) by uttam jakoji sonkamble and bairam paswan abstract: mumbi is the individual financial capital of india. the population of greater mumbai is , , and sq. km. area. the density of population , per sq. km. the dayto-day administration and rendering of public services within gr. mumbai is provided by the brihan mumbai mahanagar palika (mumbai corporation of gr. mumbai) that is a body of elected councilors on a -year team. mumcial corporation provides varies conservancy services such as street sweeping, collection of solid waste, removal and transportation, disposal of solid waste, disposal of dead bodies of animals, construction, maintance and cleaning of urinals and public sanitary conveniences. the solid waste becoming complicated due to increase in unplanned urbanization and industrialization, the environment has deteriorated significantly due to inter, intra and international migration stream to mumbai. the volume of inter state migration to mumbai is considerably high i.e. . lakh and international migrant . lakh have migrated to mumbai. present paper gives the view on solid waste management and its implications to environment and health. pollution from a wide varity of emission, such as from automobiles and industrial activities, has reached critical level in mumbai, causing respiratory, ocular, water born diseases and other health problems. sources of generation of waste are -household waste, commercial waste, institutional waste, street sweeping, silt removed from drain/nallah/cleanings. disposal of solid waste in gr. mumbai done under incineration . processing to produce organic manure. . vermi-composting . landfill the study shows that the quantity of waste disposal of through processing and conversion to organic ~anure is about - m.t. per day. the processing is done by a private agency m/s excel industries ltd. who had set up a plant at the chincholi dumping ground in western mumbai for this purpose. the corporation is also disposal a plant of its waste mainly market waste through the environment friendly, natural pro-ces~ known as vermi-composing about m.t. of market waste is disposed of in this manner at the various sites. there are four land fill sites are available and percent of the waste matter generated m mumbai is disposed of through landfill. continuous flow of migrant and increa~e in slum population is a complex barrier in the solid waste management whenever community pamc pat on work strongly than only we can achieved eco-friendly environment in mumbai. persons exposed to residential craffic have elevated races of respiratory morbidity an~ ~ortality. since poverty is an important determinant of ill-health, some h~ve argued that t~es~ assoc at ons may relate to che lower socioeconomic status of those living along ma or roads. our ob ect ve was to evaluate the association between traffic intensity at home and hospital admissions for respiratory diagnoses among montreal residents older than years. morning peak traffic estimates from the emmej montreal traffic model (motrem ) were used as an indicator of exposure to road traffic outside the homes of those hospitalised. the influence of socioeconomic status on the relationship between traffic intensity and hospital admissions for respiratory diagnoses was explored through assessment of confounding by lodging value, expressed as the dollar average over road segments. this indicator of socioeconomic status, as calculated from the montreal property assessment database, is available at a finer geographic scale than socioeconomic information accessible from the canadian census. there was an inverse relationship between traffic intensity estimates and lodging values for those hospitalised (rho - . , p vehicles during che hour morning peak), even after adjustment for lodging value (crude or . , cl % . - . ; adjusted or . , cl % . - . ). in montreal, elderly persons living along major roads are at higher risk of being hospitalised for respiratory illnesses, which appears not simply to reflect the fact that those living along major roads are at relative economic disadvantage. the paper argues that human beings ought to be at the centre of the concern for sustainable development. while acknowledging the importance of protecting natural resources and the ecosystem in order to secure long term global sustainability, the paper maintain that the proper starting point in the quest for urban sustainability in africa is the 'brown agenda' to improve che living and working environment of che people, especially che urban poor who face a more immediate environmental threat to their health and well-being. as the un-habitat has rightly observed, it is absolutely essential "to ensure that all people have a sufficient stake in the present to motivate them to take part in the struggle to secure the future for humanity.~ the human development approach calls for rethinking and broadening the narrow technical focus of conventional town planning and urban management in order to incorporate the emerging new ideas and principles of urban health and sustainability. i will examine how cities in sub-saharan africa have developed over the last fifty years; the extent to which government policies and programmes have facilitated or constrained urban growth, and the strategies needed to achieve better functioning, safer and more inclusive cities. in this regard i will explore insights from the united nations conferences of the s, especially local agenda of the rio summit, and the istanbul declaration/habitat agenda, paying particular attention to the principles of enablement, decentralization and partnership canvassed by these movements. also, i will consider the contributions of the various global initiatives especially the cities alliance for cities without slums sponsored by the world bank and other partners; che sustainable cities programme, the global campaigns for good governance and for secure tenure canvassed by unhabit at, the healthy cities programme promoted by who, and so on. the concluding section will reflect on the future of the african city; what form it will take, and how to bring about the changes needed to make the cities healthier, more productive and equitable, and better able to meet people's needs. heather jones-otazo, john clarke, donald cole, and miriam diamond urban areas, as centers of population and resource consumption, have elevated emissions and concentrations of a wide range of chemical contaminants. we have developed a modeling framework in which we first ~stimate the emissions and transport of contaminants in a city and second, use these estimates along with measured contaminant concentrations in food, to estimate the potential health risk posed by these che.micals. the latter is accomplished using risk assessment. we applied our modeling framework to consider two groups of chemical contaminants, polycyclic aromatic hydrocarbons (pah) a.nd the flame re~ardants polybrominated diphenyl ethers (pbde). pah originate from vehicles and stationary combustion sources. ~veral pah are potent carcinogens and some compounds also cause noncancer effects. pbdes are additive flame retardants used in polyurethane foams (e.g., car seats, furniture) fer sessions v and cl~ equipm~nt (e.g., compute~~· televisio~s). two out of three pbdes formulations are being voluntarily phased by mdustry due to rmng levels m human tissues and their world-wide distribution. pbdes have been .related to adv.erse neurological, developmental and reproductive effects in laboratory ijlimals. we apphed our modelmg framework to the city of toronto where we considered the southcattral area of by km that has a population of . million. for pah, local vehicle traffic and area sources contribute at least half of total pah in toronto. local contributions to pbdes range from - %, depending on the assumptions made. air concentrations of both compounds are about times higher downtown than km north of toronto. although measured pah concentrations in food date to the s, we estimate that the greatest exposure and contribution to lifetime cancer risk comes from ingestion of infant formula, which is consistent with toxicological evidence. the next greatest exposure and cancer risk are attributable to eating animal products (e.g. milk, eggs, fish). breathing downtown air contributes an additional percent to one's lifetime cancer risk. eating vegetables from a home garden localed downtown contributes negligibly to exposure and risk. for pbdes, the greatest lifetime exposure comes through breast milk (we did not have data for infant formula), followed by ingestion of dust by the toddler and infant. these results suggest strategies to mitigate exposure and health risk. p - (a) immigration and socioeconomic inequalities in cervical cancer screening in toronto, canada aisha lofters, rahim moineddin, maria creatore, mohammad agha, and richard glazier llltroduction: pap smears are recommended for cervical cancer screening from the onset of sexual activity to age . socioeconomic and ethnoracial gradients in self-reported cervical cancer screening have been documented in north america but there have been few direct measures of pap smear use among immigrants or other socially disadvantaged groups. our purpose was to investigate whether immigration and socioeconomic factors are related to cervical cancer screening in toronto, canada. methods: pap smears were identified using fee codes and laboratory codes in ontario physician service claims (ohip) for three years starting in for women age - and - . all women with any health system contact during the three years were used as the denominator. social and economic factors were derived from the canadian census for census tracts and divided into quintiles of roughly equal population. recent registrants, over % of whom are expected to be recent immigrants to canada, were identified as women who first registered for health coverage in ontario after january , . results: among , women age - and , women age - , . % and . %, rtspcctively, had pap smears within three years. low income, low education, recent immigration, visible minority and non-english language were all associated with lower rates (least advantaged quintile:most advantaged quintile rate ratios were . , . , . , . , . , respectively, p < . for all). similar gradients were found in both age groups. recent registrants comprised . % of women and had mm;h lower pap smear rates than non-recent registrants ( . % versus . % for women age - and . % versus . % for women age - ). conclnsions: pap smear rates in toronto fall well below those dictated by evidence-based practice. at the area level, immigration, visible minority, language and socioeconomic characteristics are associated with pap smear rates. recent registrants, representing a largely immigrant group, have particularly low rates. efforts to improve coverage of cervical cancer screening need to be directed to all ~omen, their providers and the health system but with special emphasis on women who recently arrived m ontario and those with social and economic disadvantage. challeges faced: a) most of the resources are now being ~pent in ~reventing the sprea.d of hiv/ aids and maintaining the lives of those already affected. b) skilled medical ~rs~nal are dymg under· mining the capacity to provide the required health care services. ~) th.e comphcat o~s of hiv/aids has complicated the treatment of other diseases e.g. tbs d) the ep dem c has led. to mcrease number of h n requiring care and support. this has further stretched the resources available for health care. orp a s d db . . i methods used on our research: . a simple community survey con ucte y our orgamzat on vo · unteers in three urban centres members of the community, workers and health care prov~ders were interviewed ... . meeting/discussions were organized in hospitals, commun.ity centre a~d with government officials ... . written questionnaires to health workers, doctors and pohcy makers m th.e health sectors. lessors learning: • the biggest-health bigger-go towards hiv/aids prevention • aids are spreading faster in those families which are poor and without education. •women are the most affected. •all health facilities are usually overcrowded with hiv/aids patients. actions needed:• community education oh how to prevent the spread of hiv/aids • hiv/aids testing need to be encouraged to detect early infections for proper medical cover. • people to eat healthy • people should avoid drugs. implications of our research: community members and civic society-introduction of home based care programs to take care of the sick who cannot get a space in the overcrowded public hospitals. prl-v a te sector private sector has established programs to support and care for the staff already affected. government provision of support to care-givers, in terms of resources and finances. training more health workers. introduction: australian prisons contain in excess of , prisoners. as in most other western countries, reliance on 'deprivation of liberty' is increasing. prisoner numbers are increasing at % per annum; incarceration of women has doubled in the last ten years. the impacts on the community are great - % of children have a parent in custody before their th birthday. for aboriginal communities, the harm is greater -aboriginal and/or torres strait islanders are incarcerated at a rate ten times higher than other australians. % of their children have a parent in custody before their th birthday. australian prisons operate under state and territory jurisdictions, there being no federal prison system. eight independent health systems, supporting the eight custodial systems, have evolved. this variability provides an unique opportunity to assess the capacity of these health providers in addressing the very high service needs of prisoners. results: five models of health service provision are identified -four of which operate in one form or another in australia: • provided by the custodial authority (queensland and western australia)• pro· vided by the health ministry through a secondary agent (south australia, the australian capital territory and tasmania) • provided through tendered contract by a private organization (victoria and northern territory) • provided by an independent health authority (new south wales) • (provided by medics as an integral component of the custodial enterprise) since the model of the independent health authority has developed in new south wales. the health needs of the prisoner population have been quantified, and attempts are being made to quantify specific health risks /benefits of incarceration. specific enquiry has been conducted into prisoner attitudes to their health care, including issues such as client information confidentiality and access to health services. specific reference will be made to: • two inmate health surveys • two inmate access surveys, and • two service demand studies. conclusions: the model of care provision, with legislative, ethical, funding and operational independence would seem provide the best opportunity to define and then respond to the health needs of prisoners. this model is being adopted in the united kingdom. better health outcomes in this high-risk group, could translate into healthier families and their communities. p - (a) lnregrated ethnic-specific health care systems: their development and role in increasing access to and quality of care for marginalized ethnic minorities joshua yang introduction: changing demographics in urban areas globally have resulted in urban health systems that are racially and ethnically homogenous relative to the patient populations they aim to serve. the resultant disparities in access to and quality of health care experienced by ethnic minority groups have been addressed by short-term, instirutional level strategies. noticeably absent, however, have been structural approaches to reducing culturally-rooted disparities in health care. the development of ethnic-specific h~alth car~ systems i~ a structural, long-term approach to reducing barriers to quality health care for eth· me mmonty populations. methods: this work is based on a qualitative study on the health care experiences of san francisco chinatown in the united states, an ethnic community with a model ethnic-specific health care infrastrucrure. using snowball sampling, interviews were conducted with key stakeholders and archival research was conducted to trace and model the developmental process that led to the current ethnic-specific health care system available to the chinese in san francisco. grounded theory was the methodology ijltd to analysis of qualitative data. the result of the study is four-stage developmental model of ethnic-specific health infrastrueture development that emerged from the data. the first stage of development is the creation of the human capital resources needed for an ethnic-specific health infrastructure, with emphasis on a bilingual and bicultural health care workforce. the second stage is the effective organization of health care resources for maximal access by constituents. the third is the strengthening and stability of those institutional forms through increased organizational capacity. integration of the ethnic-specific health care system into the mainstream health care infrastructure is the final stage of development for an ethnic-specific infrastructure. conclusion: integrated ethnic-specific health care systems are an effective, long-term strategy to address the linguistic and cultural barriers that are being faced by the spectrum of ethnic populations in urban areas, acting as culturally appropriate points of access to the mainstream health care system. the model presented is a roadmap to empower ethnic communities to act on the constraints of their health and political environments to improve their health care experiences. at a policy level, ethnic-specific health care organizations are an effective long-term strategy to increase access to care and improve qualiiy of care for marginalized ethnic groups. each stage of the model serves as a target area for policy interventions to address the access and care issues faced by culturally and linguistically diverse populations. users in baltimore md: - noya galai, gregory lucas, peter o'driscoll, david celentano, david vlahov, gregory kirk, and shruti mehta introduction: frequent use of emergency rooms (er) and hospitalizations among injection drug users (idus) has been reported and has often been attributed to lack of access to primary health care. however, there is little longitudinal data which examine health care utilization over individual drug use careers. we examined factors associated with hospitalizations, er and outpatient (op) visits among idus over years of follow-up. methods: idus were recruited through community outreach into the aids link to lntravenous experience (alive) study and followed semi-annually. , who had at least follow-up visits were included in this analysis. outcomes were self-reported episodes of hospitalizations and er/op visits in the prior six months. poisson regression was used accounting for intra-person correlation with generalized estimation equations. hits: at enrollment, % were male, % were african-american, % were hiv positive, median age was years, and median duration of drug use was years. over a total of , visits, mean individual rates of utilization were per person years (py) for hospitalizations and per py for er/op visits. adjusting for age and duration of drug use, factors significantly associated with higher rates of hospitalization included hiv infection (relative incidence [ri(, . ), female gender (ri, . ), homelessness (ri, . ), as well as not being employed, injecting at least daily, snorting heroin, havmg a regular source of health care, having health insurance and being in methadone mainte.nance treatment (mmt). similar associations were observed for er/op visits except for mmt which was not associated with er/op visits. additional factors associated with lower er/op visits were use of alcohol, crack, injecting at least daily and trading sex for drugs. % of the cohort accounted for % of total er/op visits, while % of the cohort never reported an op visit during follow-up. . . . lgbt) populations. we hypothesized that prov dmg .appomtments .for p~t ~nts w thm hours would ensure timely care, increase patient satisfaction, and improve practice eff c ency. further, we anticipated that the greatest change would occur amongst our homeless patients.. . methods: we tested an experimental introduction of advanced access scheduling (usmg a hour rule) in the primary care medical clinic. we tracked variables inclu~ing waiting ti~e fo~ next available appointment; number of patients seen; and no-show rates, for an eight week penod pnor to and post introduction of the new scheduling system. both patient and provider satisfaction were assessed using a brief survey ( questions rated on a -pt scale). results and conclusion: preliminary analyses demonstrated shorter waiting times for appointments across the clinic, decreased no-show rates, and increased clinic capacity. introduction of the advanced access scheduling also increased both patient and provider satisfaction. the new scheduling was initiated in july . quantitative analyses to measure initial and sustained changes, and to look at differential responses across populations within our clinic, are currently underway. introduction: there are three recognized approaches to linking socio-economic factors and health: use of census data, gis-based measures of accessibility/availability, and resident self-reported opinion on neighborhood conditions. this research project is primarily concerned with residents' views about their neighborhoods, identifying problems, and proposing policy changes to address them. the other two techniques will be used in future research to build a more comprehensive image of neighborhood depri· vation and health. methods: a telephone survey of london, ontario residents is currently being conducted to assess: a) community resource availability, quality, access and use, b) participation in neighborhood activities, c) perceived quality of neighborhood, d) neighborhood problems, and e) neighborhood cohesion. the survey instrument is composed of indices and scales previously validated and adapted to reflect london specifically. thirty city planning districts are used to define neighborhoods. the sample size for each neighborhood reflects the size of the planning district. responses will be compared within and across neighborhoods. data will be linked with census information to study variation across socio-eco· nomic and demographic groups. linear and gis-based methods will be used for analysis. preliminary results: the survey follows a qualitative study providing a first look at how experts involved in community resource planning and administration and city residents perceive the availability, accessibility, and quality of community resources linked to neighborhood health and wellbeing, and what are the most immediate needs that should be addressed. key-informant interviews and focus groups were used. the survey was pre-tested to ensure that the language and content reflects real experiences of city residents. the qualitative research confirmed our hypothesis that planning districts are an acceptable surrogate for neighborhood, and that the language and content of the survey is appropriate for imple· mentation in london. scales and indices showed good to excellent reliability and validity during the pre· test (cronbach's alpha from . - . ). preliminary results of the survey will be detailed at the conference. conclusions: this study will help assess where community resources are lacking or need improve· ment, thus contributing to a more effective allocation of public funds. it is also hypothesized that engaged neighborhoods with a well-developed sense of community are more likely to respond to health programs and interventions. it is hoped that this study will allow london residents to better understand the needs and problems of their neighborhoods and provide a research foundation to support local understandmg of community improvement with the goal of promoting healthy neighborhoods. p - (a) hiv positive in new york city and no outpatient care: who and why? hannah wolfe and victoria sharp introduction: there are approximately million hiv positive individuals living in the united sta!es. about. % of these know their hiy status and are enrolled in outpatient care. of the remaining yo, approx~mately half do not know their status; the other group frequently know their status but are not enrolled m any .sys~em of outpatient care. this group primarily accesses care through emergency departments. when md cated, they are admitted to hospitals, receive acute care services and then, upon poster sessions v di 'harge, disappear from the health care system until a new crisis occurs, when they return to the emergency department. as a large urban hiv center, caring for over individuals with hiv we have an active inpatient service ".'ith appr~xi~.ately discharges annually. we decided to survey our inpatients to better charactenze those md v duals who were not enrolled in any system of outpatient care. results: % of inpatients were not enrolled in regular outpatient care: % at roosevelt hospital and % at st.luke\'s hospital. substance abuse and homelessness were highly prevalent in the cohort of patients not enrolled in regular outpatient care. % of patients not in care (vs. % of those in care) were deemed in need of substance use treatment by the inpatient social worker. % of those not in care were homeless (vs. % of those in care.) patients not in care did not differ significantly from those in me in terms of age, race, or gender. patients not in care were asked "why not:" the two most frequent responses were: "i haven't really been sick before" and "i'd rather not think about my health. conclusions: this study suggests that there is an opportunity to engage these patients during their stay on the inpatient units and attempt to enroll them in outpatient care. simple referral to an hiv clinic is insufficient, particularly given the burden of homelessness and substance use in this population. efforts are currently underway to design an intervention to focus efforts on this group of patients. p .q (a) healthcare availability and accessibility in an urban area: the case of ibadan city, nigeria in oder to cater for the healthcare need of the populace, for many years after nigeria's politicl independence, empphasis was laid on the construction of teaching, general, and specialist hospital all of which were located in the urban centres. the realisation of the inadequacies of this approach in adequately meeting the healthcare needs of the people made the country to change and adopt the primary health care (phc) system in . the primary health care system which is in line with the alma ata declaration of of , wsa aimed at making health care available to as many people as possible on the basis of of equity and social justice. thus, close to two decades, nigeria has operated primary health care system as a strategy for providing health care for rural and urban dwellers. this study focusing on urban area, examimes the availabilty and accessibility of health care in one of nigeria's urban centre, ibadan city to be specific. this is done within the contest of the country's national heath policy of which pimary health care is the main thrust. the study also offers necessary suggestion for policy consideration. in spite of the accessibility to services provided by educated and trained midwifes in many parts of fars province (iran) there are still some deliveries conducted by untrained traditional birth attendants in rural parts of the province. as a result, a considerable proportion of deliveries are conducted under a higher risk due to unauthorised and uneducated attendants. this study has conducted to reveal the pro· portion of deliveries with un-authorized attendants and some spatial and social factors affecting the selection of delivery attendants. method: this study using a case control design compared some potentially effective parameters indud· ing: spatial, social and educational factors of mothers with deliveries attended by traditional midwifes (n= ) with those assisted by educated and trained midwifes (n= ). the mothers interviewed in our study were selected from rural areas using a cluster sampling method considering each village as a cluster. results: more than % of deliveries in the rural area were assisted by traditional midwifes. there are significant direct relationship between asking a traditional birth attendant for delivery and mother age, the number of previous deliveries and distance to a health facility provided for delivery. significant inverse relationships were found between mother's education and ability to use a vehicle to get to the facilities. conclusion: despite the accessibility of mothers to educated birth attendants and health facilities (according to the government health standards), some mothers still tend to ask traditional birth attendants for help. this is partly because of unrealistic definition of accessibility. the other considerable point is the preference of the traditional attendants for older and less educated mothers showing the necessity of changing theirs knowledge and attitude to understand the risks of deliveries attended by traditional and un-educated midwifes. p - (a) identification and optimization of service patterns provided by assertive community treatment teams in a major urban setting: preliminary findings &om toronto, canada jonathan weyman, peter gozdyra, margaret gehrs, daniela sota, and richard glazier objective: assertive community treatment (act) teams are financed by the ontario ministry of health and long-term care (mohltc) and are mandated to provide treatment, rehabilitation and support services in the community to people with severe and persistent mental illness. there are such teams located in various regions across the city of toronto conducting home visits - times per week to each of their approximately respective clients. each team consists of multidisciplinary health professionals who assist clients to identify their needs, establish goals and work toward them. due to complex referral patterns, the need for service continuity and the locations of supportive housing, clients of any one team are often found scattered across the city which increases home visit travel times and decreases efficiency of service provision. this project examines the locations of clients in relation to the home bases of all act teams and identifies options for overcoming the geographical challenges which arise in a large urban setting. methods: using geographic information systems (gis) we geocoded all client and act agency addresses and depicted them on location maps. at a later stage using spatial methods of network analysis we plan to calculate average travel rimes for each act team, propose optimization of catchment areas and assess potential travel time savings. resnlts: initial results show a substantial scattering of clients from several act teams and substan· rial overlap of visit travel routes for most teams. conclusions: reallocation of catchment areas and optimization of act teams' travel patterns should lead to substantial savings in travel times, increased service efficiency and better utilization of resourc_~· ~e l'<!tenri~i modifications to catchment areas must be conducted with appropriate attention to specific clients servtce needs, service continuity and applicable regulations by the mohl tc. venice lido is a popular island within and outside italy because it hosts the international cinema festival yearly. only few people remember the island for its hospital, which, in the fifties, was one of the most important hospitals in italy and in europe, being a modern center for wind-, sun-and thermal-therapy. since the sixties, its fame became to drop away, since its structure was no longer adequate for the evolving medicine science. at the end of the seventies all the wards were moved into a new big building in the same area. at present the hospital is made up by about forty 'pavilions' (mostly partially used or empty) and a big building, disseminated in a hectares area, on the sea front, on the m long beach. the aim of my research is to suggest a realistic solution, sustainable on the functional use of the area according to basic local needs and economically realizable. i used a philological and multi-disciplinary method, more in detail: -from historical documents, i found what was the very first call of the property and how it adapted to the needs of the demographic development and the sanitary supply over time; -by contacting some operators from different fields, i realized which functions were suitable to the buildings in existence, to the population's needs and to the present sanitary supply. moreover the planning idea considers: -the debate going on between local people who strongly want to preserve the property, and die ones who want to renew it by different new opportunities; and -the regional sanitary politics, aiming at rationalizing the regional hospitals dislocation, and the budget needs. this plan analyzes and proposes some new alternative solutions to satisfy different needs. the different activities will be dealt out and the environmental fall will be limited as much as possible. after having analyzed its basic call, considered its environmental peculiarities and its position, verified the emerging needs of the local population, the plan proposes different activities: the hospital; the social-rehabilitation center; the elderly house; the thermal center; the residential center; and other activities. such a plan wants to share in the solution of a basic problem by giving architectonic and functional dignity to an historical completely degraded area and by starting again a social-economical broken off process, by bringing in venice lido some fresh necessary elements for its so wished new throw. p - (c) dilemma of free health care in spokane, wa david bunting introduction: the paper reports on the activities of project access spokane [pas], a physician sponsored initiative to provide uncompensated health care to low income, uninsured residents of spokane county wa. program providers included all county hospitals, over physicians, other medical professionals, and specialized clinics. each prescription requires only a $ co-payment. sponsored and administered by the county medical society, pas is funded by local and national foundations, private corporations, municipalities, civic organizations and individuals. method: the paper is based on a first year assessment report funded by pas, using hcfa [health care financing administration] insurance claim data documenting utilization rates, disease categories and donated charge information and patient cares [centralized applications, referrals and enrollment status) data. results: while essentially free for enrollees, the program involved real costs. an administrative organization to refer over patients to any of over providers had to be developed and staffed, using both paid and unpaid personnel. methods to identify potential patients and veri.fy eligibility. had to ~devised. patient appointments and transportation had to be scheduled and monitored. pu~hc relanons, provider solicitations and fundraising activities were continuous. information requirements regarding program operation were also significant. data reporting the volume. ~nd value of dona~ed medical services were necessary to demonstrate accomplishments and attr~ct addmon~l support. providers required assurances their contributions were both significant and eqmtable. funding sources sought evidence that their support had important consequences. however, generating this ~~ta proved difficult. many providers failed to submit appropriate insurance claims forms because .of a~dmonal donated effort and administrative cost, thereby not only reducing their own apparent conmbut ons but also the overall significance of the program. conclusions: during its initial year, the estimated cost to deliver free health care was ~bout per enrollee. the lesson is that without an elaborate administrative structure and record keeping s.yst~~· efforts to provide free health care probably will fail. eligible enrollees c~n not be ~parated from in~hgi ble ones, care will not be accessed or delivered in an efficient manner, neither fundmg nor ~upport "". be offered without evidence of tangible benefits, and providers will withdraw if they perceive mequ table tteannent. v p - s (c) mobility in prostitution and the impact of health therese van der helm and henk sulman poster sessions introduction: many of the estimated . commer~ial ~ex wor~ers (c~w)in a'.' ~terdam ~~me from developing countries and eastern europe. to gain ins~ght mto their workmg and_ hvmg condinons the intermediary project (ip) at the municipal health serv ~e _contacts these women via ?utreach work on regular basis. since the new brothel law in october s ~troduc~d, ~sw ~rom outside the eu and who have no dutch residence permit are not allowed to work m prost tut n. smee then, many of these csw therefore have gone "underground." the consequences of the new law in the netherlands will be discussed with regard to the accessibility of csw and their risk for stl/hiv acquisition and unplanned pregnancies. methods: topics during outreach work are the interventions to increase the knowledge of safe sex and birth control for csw. written information is handed out in relevant languages and with addresses of health and social services. in conversations with the women, it appeared that many are not aware of these services. to provide easier access to health care for women, staff of the ip carries out free sti control csw working places, in windows brothels and sex houses. also, women are offered vaccination against hepatitis b (hbv). results: from january till july we approached csw for first contact. one third was dutch; others were from developing countries, other eu countries and eastern europe. sti consul· rations were done among non-iv drug using sex workers, of whom % was dutch. of these, % was diagnosed with syphilis, % with gonorrhea, and % with chlamydia. of women tested for hiv, none were infected. due to the high turnover of csw in .brothels, most wnmen were tested only once. among csw tested for hbv -of whom one third is dutch - % had antibodies for hbv, were carrier of hbv, most of whom came from hbv endemic areas. conclusions: sti control and hbv vaccination in brothels is an important support in health care. our findings suggest that csw do not play an important role in the transmission of sti. many csw are highly mobile and often not aware of the existing health and social services. continuous outreach is important to remain in contact with this mobile population. regulations in the new brothel law should not hamper contacts with (illegal) csw. heart disease (cho) is projected to become the leading cause of death. studies conducted in europe and the united states have proven a higher rate of cho in south asians who have migrated from south asia, most notably india, pakistan and bangladesh. approximately % of all heart attacks among south asian men occur under the age of ; % of them occur under the age of -unheard of in any other population. associated risk factors such as diabetes, high blood pressure and cholesterol are also com· mon in this group. the population of south asians residing in nyc has more than doubled over the past decade to over , , the majority being young, working-class and with limited health care access. many south asian men are employed as taxi drivers ( out of nyc taxi drivers are from south asial, working daily hour plus shifts. methods: acknowledging that this vulnerable, at-risk group was unavailable for outreach through conventional venues, three of the hospitals of the new york city health and hospital corporation, (elmhurst, queens and bellevue) conducted a one day outreach effort at nyc's jfk international air· ~rt's taxi holdin~ ar~a, ~here over one thousand taxis regularly assemble. bringing an outreach event directly to the taxi dnvers workplace, a tent was set up where cardiovascular-related health screenings, in~luding bl~ pressure, sugar, cholesterol, body mass index (bmi), were provided. results were shared with and explamed to the drivers and each participant received a south asian health education brochure. a total of taxi drivers who identified as south asian were involved. rau/ts: participants were all male, ranging from to years; mean age, . . screenings revealed % hypertensive; % had cholesterols over ; % blood glucose over ; % had a bmi greater than . conc~on: a unique outreach activity, adapting to logistical, occupational limitations, is pre· se~ted. on-site f~back and explanation of results, reiterating and reinforcing the concern that south asia~. men are at mcreased danger for early coronary heart disease, and the dissemination of a culturally sensmve and r~levant brochure, may heighten awareness of prevailing cardiac risk factors in this immi· grant community. p - (c) the community-hospital integration program framework: community-hospital panoenhips to improve the population's health john stevenson, richard blickstead, ann-marie marcolin, and sandi kendal v introduction: st. josephs health centre is a catholic community teaching hospital located in the heart of southwest toronto. st. joseph\'s was founded from a community-expressed need for hospital services, and since then has stayed committed to fostering a healthy community through collaboration and parmership. st. joseph's has developed an innovative model, the community-hospital integration program (chip), to strengthen st. joseph's partnerships with community stakeholders, and facilitates the building of links between community needs, service provision, and public policy outcomes to improve the health and wellness of the diverse neighbourhoods they together serve. methods: development of the chip framework st. joseph's health centre developed the chip framework through a multidisciplinary approach that included extensive international literature reviews, consultations, and key informant interviews with community service agencies and academics. to ensure active community voice, st. joseph's has hosted a number of community consultations including a community outreach forum attended by over ninety representatives from community partners. results: the chip framework the chip framework aims to improve the health and wellness of the urban communities served by st. josephs health centre through four intersecting pillars: • raising community voices provides an infrastructure and process that supports community stakeholder input into health care service planning, decision-making, and delivery by the hospital and across the continuum of care; • sharing reciprocal capacity promotes healthy communities through the sharing of our intellectual and physical capacity with our community partners; • cultivating integration initiatives facilitates vertical, horizontal, and intersectoral integration initiatives in support of community-identified needs and gaps; and • facilitating healthy exchange develops best practices in community integration through community-based research, and facilitates community voice in informing public policy. the chip framework drives the complex inter-relationships between community-hospital engagement, reciprocal capacity-building, integration initiatives, and community-based research and evaluation, to create an interconnected network of health care services. the fluidity and simplicity of this framework, and its dedication to balancing community needs and hospital mandate, posits the st. josephs health centre's chip model as an integral component in building healthy and thriving communities. p - (c) home based care promotion: improving acess to quality services and livelihood in the face of aids home based care is a service provided to persons affected/living with hiv/aids, a menu of care/support services at home/community. it is a prominent alternative approach. in uganda, hospital bed ocupacny is high, patient health care worker ratio deteriorating. empowering communities offers solutions to the problems; adressing cost, effectiveness of care. hiv/aids demands changes in attitudes, behaviour, approaches which is enhanced in home/community settings. for example art requires high levels of adherecnce, which medical workers have vety little opportunity to enforce. it also demands other support mechanisims in terms of nutrition, personal displine, etc which work best in stigma free environments. hence the relevance of home based care. this paper highlights the gaps that call for increased action in terms of home based care, examples of whre it has worked key challenges and recommendations for the future. p - (c) health care for one ... health care for alli katharina kovacs burns introduction: at the surface, it appears that every person in canada _has. ~ccess to a publicly funded health care system. those living in urban centers should have the best ava l~b hty, chmce, and access to a variety of health care services because of the distribution of health care services, fac lmes, and health professionals in concentrated in urban centers. this is not true for everyone -people with low income or who are homeless experience the challenges of social exclusion and being marginalized: there are many factors at play making it difficult for the latter group of people to access health care. service they need,.when they need them. health care is not as accessible or inclusive as intended. the quesuon to be explore.cl ~: if health care is available and accessible to one person, what makes it not available to all people? the ~ gmfic~nce of having marginalized people accessing health care and other services includes e~hanced quality of hfe and decreased risks associated with being homeless, and cost savings in ion~ ter~ w rh acute health care. methodology: community-based participatory research is applied m a case study on health care access and challenges experienced by low income and homeless people in one urban centre, edmonton, edmonton, and their challenges. the data is being gathered and ana_lyzed usmg basic m x~d methods. results: the results will focus on how services can be more mtegrated and accessible to all people with low income and who are homeless. there will also be discussion about specific perceptions of not only the service providers but also of people with low income an~ who are homeless~ and vario~s decision makers. the results will be compared to the literature regardmg health care services access mother urban centers in canada and elsewhere. conclusions: recommendations will need to address social exclusion and other factors which can make health care and other services more available to all people in the community. the implications for health care will also be discussed. additional information will be gathered in the next phases of the study to develop a community services access model. p - (c) availability and access exemplified: a case study beth hayhoe and ruth ewert introduction: access to health care in canada requires either the correct documentation or money. street youth have neither. in addition, health services in canada are designed by adults for adults. youth in general are often wary of having trust in adults with respect to their health concerns and frequently feel misunderstood. street youth are even more mistrustful of adults and public organizations, making their contact with health care professionals minimal. this combined with their risky behaviours and dangerous environment creates a population at risk for numerous health issues but with no place to have them investi· gated. at our non-government, not for profit health service designed specifically to provide a broad range of health care to street youth, professional services are provided almost entirely by volunteers. methods: using a retrospective analysis of the years of data gathered from this organization and reviewing the initial reasons gathered from youth about their needs, the success of the health centre was examined. results: all the things youth had listed as being important in a health centre have been implemented, and even more things have been added to improve the breadth and quality of services offered. the use of the health centre has increased by more than six times since its opening in . in addition, tens of thousands of visits have been paid to the health centre, costing the government and taxpayers nothing. as far as we know there is nothing else in canada that offers so many diverse and innovative services to youth in need. conclusion: it is clear from this case, that health care targeted at the needs of specific disadvan· taged populations can successfully provide them with appropriate health care. a model of accessible health care for marginalized populations can easily be developed for high impact and low cost from this successful case. toronto is one of the most ethno-racially diverse cities in the world of the estimated , , toronto residents, % ( , ) live in scarborough population growth in scarborough is faster than toronto. scarborough's population increased by % from to while toronto increased only by %. toronto's population is projected to increase by % ( ) in while scarbor· ough's will increase by %. (census canada ) low income, pove;ty, seniors, hidden homeless, new~omers to canada, the uninsured, are just a few of the issues concerning health care in our community. health care needs in scarborough are greatly impacted by diversity of ethnic and racial groups, poverty and settlement issues. this paper will share how the scarborough hospital (tsh) an urb~n communir_y hospital cares f~~ it~ community. tsh recognizes: •the changing community• b_arriers t~ accessing care • lnequalmes m health care the hospital in caring for its community pro· v ~es services that '!'e~e cu~turally, racially, and linguistically sensitive to our community. the paper will share the hospitals unique program on access and equity. the paper will share the needs in scar· borough and tsh's response to these needs: working in partnership with the local health committee, i:ne scarborough homeless co.mminee, the scarborough network of immigrant services organiza· nons a~d others. :' e paper will also share the many initiatives this urban community hospital has taken viz. community and home programs in service areas such as mental health, haemodialysis day care, t~~ home oxyg~n program, the palliative at-home program, and above all support for the volunteer clinic for the uninsured. j"'" tllu:lion: in canada's universal health care system it is generally assumed that everyone has equal access to health care. however, some immigrant groups in canada have historically been uninswed. these groups include failed refugee claimants, those overstaying their visas, and new immigrants in transition who are waiting to become eligible for health insurance. some estimates have suggested that at the present time there may be as many as one hundred thousand undocumented and thus uninsured immigrants in toronto alone. understandably, information on the characteristics of this marginalized population is very limited, since undocumented immigrants tend to have little contact with formal institutions. knowledge of the demographic characteristics of this population may aid in the development of health and social programs to better identify and meet the needs of undocumented immigrants in toronto. we conducted a review of all undocumented, uninsured patients, years of age or older at access alliance multicultural community health centre (aamchc) between and . demographic information such as age, gender, preferred language, length of time living in canada, selfreported education level and household income were recorded. rmdts: % of all adult patients at access alliance were undocumented and uninsured. % were under years of age (with a median age of years), % were women and only % spoke english. this group lived in canada for an average period of . years before they were first seen at aamchc. % of undocumented clients reported having completed at least a secondary or post-secondary education. % had self-reported household incomes of less than , $/year, while % of households reported earning less than $ , /year. the mean income per person in an average household was $/month. conchuions: uninsured individuals at aamchc were predominantly young females with limited knowledge of the english language. despite having attained a high level of education most were living well below the poverty line. recognition of these characteristics may assist in the development of health and social programs that are better adapted to meet the needs of undocumented immigrants. p - (c) sharing expertise: a role for the hospital lactation consultant in the community. badrgrmuul: st. michael's hospital is a tertiary care hospital that serves a large inner city population in downtown toronto. in order to provide care to this population, the hospital has developed a number of unique outreach roles. one such role was developed to work with pregnant and breastfeeding women living in regent park, a social housing complex located near the hospital. the population of regent park includes new immigrants, refugees and the socially disadvantaged. approach: the outreach lactation consultant provides care, as part of the canada prenatal nutrition program, in the community prenatally, in the hospital during their inpatient stay and postnatally when they return to the community. the continuity of care enhances the probability of long term successful breastfeeding. aside from the health benefits of breastmilk, breastfeeding is especially important for women who are financially needy and must depend on food banks for formula. . . lason learned: aher two years of partnership, the relationship between the an-hospital ~stpar tum experience for breastfeeding mothers and the community postpartum support, the breastfeeding rate ~thin this community is high. the professional support and visibility of the : ctation consultant, both m the hospital and in the community, contributes to the support of breastfee~m~.. . in light of ongoing funding constraints, this ha son between hospital and community could be at risk and discontinued. in light of the benefits to the mother/baby dyad, the lactation consultant as a community partner in the canada prenatal nutrition program should be safeguarded. . lldpodiu:tion: although the importance of adequate health care in pregna~cy is well recognised, ethnic disparities in utilization of prenatal care still exist in many western coun~~es. a fun~amental factor in these disparities may be language proficiency, as it influences women's ab hty. to ob~m and understand health information, to find the way in the health care system and to communicate with health care v poster sessions providers. we investigated the role of language proficiency in use and knowledge of folic acid as aspect of prenatal care in an urban multi-ethnic pregnancy c?hort. . . design: prospective cohort study. setting and parnc pants: amsterdam ~regnant women attending obstetric care providers for their first antenatal visit (n= ). country of birth defined ethnicity: the netherlands, surinam, antilles, turkey, morocco, ghana, other non-~est~m (nw) and other western (w) country. main outcome measures: knowledge about and use of.fohc a~d (fa) supplements in pregnancy, and determinants of these in diffe~~t ethnic ~~ups. deterrrunants mcl~ded age, ed~ tion, parity, pregnancy intention and dutch prof c ency. stansncs: ~ to co~p~re e~c groups, stranfied logistic regression (forward stepwise method) to explore determmants "'.'thm ethmc groups .. use of fa supplements was significantly lower among ghanaian, moroccan, turkish and other nw women ( %to %) than among dutch ( %) or other w women ( %). use amongsurinames and antillean women was intermediate ( %and %). ethnic differences in fa knowledge were similar. knowledge was the strongest determinant of use in all ethnic groups, with odds ratios (ors) ranging from . to . . language proficiency was the strongest determi~a~t of kno~ledge in ethnic groups with a mother tongue different from dutch (ors good vs. low proficiency ranging from . ro . ). educational level had a modifying role, as shown by an interaction effect between education and language proficiency in the nw group. here, the odds of having fa knowledge given a high education and good dutch proficiency was times the odds given a good proficiency but low education. conclusions: appropriate periconceptional use of folic acid supplements in non-western ethnic groups is low, reflecting an absence of knowledge that is largely determined by the inability to speak and understand the language of the habitual country. tailored interventions using communication channels most likely to address (pregnant) women from ethnic minority groups are necessary. apan from specific interventions, our results are in support of strong incentives on language education despite current political debate. introduction: recent research suggests living in an economically disadvantaged neighborhood is asso· ciated with decreased likelihood of undergoing mammography and increased risk of late-stage breast can· cer diagnosis. long distances and travel times to facilities offering low-or no-cost mammography may be imponant barriers to adherence to mammography screening recommendations for residents of economically disadvantaged neighborhoods. the purpose of this study was to examine whether facilities providing low-and no-cost screening mammography were less spatially accessible in low-income neighborhoods in chicago, and the extent to which the relationship between neighborhood income and the spatial accessibility of facilities varied by the proponion of african-american residents in the neighborhood. methods: the sample consisted of chicago neighborhoods. for each neighborhood, we con· structed three measures of the spatial accessibility of facilities: street network distance to the nearest facility, public transportation travel time to the nearest facility, and shortest automobile travel time to a facility. using decennial census data, we characterized the neighborhoods according to proportion of residents with incomes below the poverty line, proportion of residents in each of four raciavethnic groups (african-american, latino, white, and other), and population density. we used ordinary least squares (ols) and spatial exogenous lag regression to examine relationships. model estimated the relationship between neighborhood poverty and the spatial accessibility of facilities, adjusting for raciaveth· nic composition and population density. model added a multiplicative interaction term between neighborhood poverty and african-american. restllts: we identified deven facilities that provided low-or no-cost screening mammography to chicago residents in . we found that the distance and travel times via automobile and public trans· portation to facilities generally decreased as neighborhood poveny increased. however, we also found that the ~egative associations between neighborhood poverty and two of the spatial accessibility mea· sures -distance and public transportation travel time -were less strong in neighborhoods with the highest proponions of african-american residents. among neighborhoods in the highest tertile for poveny, th~ mean distance and mean public transportation travel time to facilities were over twice as long in neighborhoods in the highest tertile than in those in the lowest tenile of african-american residents. . ~ persistent socioeconomic and racial/ethnic disparities in breast cancer stage at diagno-s ~nd su~ val suggest that ensuring an equitable distribution of affordable mammography is a worth-w~e policy .goal. the ~~dy sugges~ that ~ture investigations should consider both neighborhood soc oecono d c charactensbes and rac avethmc composition when examining the spatial distribution of health resources. , ) . epidemiological data suggest tha~ hiv prevalence among msm is over % in some metropolitan cities, such .as beijing (ibid.). due to widespread homophobia in chinese society, however, this population remains invisible within current health/social services. lack of research on sexuality, specifically homosexuality, has impaired our understanding of health and health practices of chinese msm. focusing on the illness experiences of chinese msm with hiv/aids, this paper explores the socio-cultural impacts of hiv/ aids on this group. the data used for this paper were collected through semi-constructed in-depth face-toiace interviews with adult plwhas (including msm) in beijing, china. with the permission of the participants, the interviews were audio-taped or recorded in notes. the transcribed interviews and interview notes were analyzed by using n-vivo, a software program for qualitative data analysis. this phenomenological study aimed to understand the experiences chinese plwhas (including msm) from their own perspectives. results: it is found that the illness experiences of chinese msm with hiv/aids are profoundly shaped by the socio-cultural meanings of homosexuality, which are further complicated by the dominant discourses on hiv/aids in china. at a macro level, homophobia in the larger society has decreased the capability of this group to respond to this epidemic in a more efficient way. at a meso level, aids-phobia within the chinese msm circuits has prevented this group from openly confronting this disease and offering support to those who are already affected by it. at a micro level, however, these hiv-infected/ affected msm have tried their best to locate spaces to live and to construct hope for their future lives despite various barriers within family, community, and the larger society. this study suggests that facilitating chinese msm's response to the aids crisis urgently requires bridging awareness, commitment, knowledge and resources both within and without this group. it also illustrates the importance of understanding homosexuality in the local context of hiv i aids, which will be helpful for developing culturally sensitive hiv/aids programs for this population on the community, national and international levels. introduction: having a regular family doctor (rfd) is known to be positively correlated with a good medical follow up, including access to preventive and/or chronic care. inversely, a lack of primary care may lead to high rates of avoidable hospitalizations, especially among poor people and/or in underserved neighbourhoods. in such a matter, a recent comparative study showed that paris was better ranged than other cities, such as nyc, tokyo or london. nevertheless, despite a quasi universal health insurance and a high density of general practitioners, a noticeable fraction of the paris population does not have any regular physician and we aimed to understand who they are and for what reasons rhey don't have any rfd. mdbods: cross sectional population survey among a random sample of households in ~nderpriv ileged neighbourhoods in paris inner city, performed in , using a face-to-face quest nna re collecr- ng more than social and health characteristics. ruults: a quarter ( . %) of rhe study popularion did not have any rfd. this proporrion was iignificantly higher among male (or= . , %ci = [ . - . ), younger (e.g. or - /> .s l _= ._oo, " .ci = ( . - . )), and/or unemployed (or = . , %ci = ij . - . _ people. in multtvanate analysis, after a full adjustment on gender, age, health status, health insura~ce, income, occupat n and tducation level, we observed significant associations between having no rfd and: ~arrtal and_ pare~t hood status (e.g. or single no kids/in couple+kids = . , %ci = ( . - . ()~ quality of relattonsh ps with neighbours (or bad/good= . , %ci = [ . - . )), and length of residence m the neighbourhood (with a dose/effect statistical relationship). . co clusion: gender, age, employment status, mariral and parenthood stat~s as well as ~e gh bourhood anchorage seem to be major predictors of having a rfd, even when um.versa! health i~sur ance has reduced most of financial barriers. in urban contexts, where residential migrattons and single lift (or family ruptures) are frequent, specific information may be conducted to encourage people to ket rfd. :tu~y tries to assess the health effects and costs and also analyse the availability and accessibility to health care for poor. . methods: data for this study was collected by a survey on households of the local community living near the factories and households where radiation hazard w~s n?~ present. ~~art from mor· bidity status and health expenditure, data was collected ~n access, a~ail~b .hty and eff c ency of healrh care. a discriminant analysis was done to identify the vanables that d scnmmate between the study and control group households in terms of health care pattern. a contingent valuation survey was also undertaken among the study group to find out the factors affecting their willingness to pay for health insurance and was analysed using logit model. results: the health costs and indebtedness in families of the study group was high as compared to control group households and this was mainly due to high health expenditure. the discriminant analysis showed that expenditure incurred by private hospital inpatient and outpatient expenditure were significant variables, which discriminated between the two types of households. the logit analysis showed !hat variables like indebtedness of households, better health care and presence of radiation induced illnesses were significant factors influencing willingness to pay for health insurance. the study showed that study group households were dependent on private sector to get better health care and there were problems with access and availability at the public sector. conclusion: the study found out that the quality of life of the local community is poor due to health effects of radiation and the burden of radiation induced illnesses are so high for them. there is an urgent need for government intervention in this matter. there is also a need for the public sector to be efficient to cater to the needs of the poor. a health insurance or other forms of support to these households will improve the quality for health care services, better and fast access to health care facilities and reduces the financial burden of the local fishing community. the prevalence of substance abuse is an increasing problem among low-income urban women in puerto rico. latina access to treatment may play an important role in remission from substance abuse. little is known, however, about latinas' access to drug treatment. further, the role of social capital in substance abuse treatment utilization is unknown. this study examines the relative roles of social capital and other factors in obtaining substance abuse treatment, in a three-wave longitudinal study of women ages - living in high-risk urban areas of puerto rico, the inner city latina drug using study (icldus). social capital is measured at the individual level and includes variables from social support and networks, familism, physical environment, and religion instruments of the icdus. the study also elucidates the role of treatment received during the study in bringing about changes in social capital. the theoretical framework used in exploring the utilization of substance abuse treatment is the social support approach to social capital. the research addresses three main questions: ( t) does social capital predict parti~ipating in treatment programs? ( ) does participation in drug treatment programs increase social capital?, and ( ) is there a significant difference among treatment modalities in affecting change in ~ial capital? the findings revealed no significant association between levels of social capital and gettmg treatment. also, women who received drug treatment did not increase their levels of social capital. the findings, however, revealed a number of significant predictors of social capital and receiving drug ~buse treatment. predictors of social capital at wave iii include employment status, total monthly mcoi:rie, and baseline social capital. predictors of receiving drug abuse treatment include perception of physical health and total amount of money spent on drugs. other different variables were associated to treatment receipt prior to the icldus study. no significant difference in changes of social capital was found among users of different treatment modalities. this research represents an initial attempt to elucidate the two-way relationship between social capital and substance abuse treatment. more work is necessary to unden~nd. ~e role of political forces that promote social inequalities in creating drug abuse problems and ava lab hty of treatment; the relationship between the benefits provided by current treatment poster sessions v sctrings and treatment-seeking behaviors; the paths of recovery; and the efficacy and effectiveness of the trtaanent. and alejandro jadad health professionals in urban centres must meet the challenge of providing equitable care to a population with diverse needs and abilities to access and use available services. within the canadian health care system, providers are time-pressured and ill-equipped to deal with patients who face barriers of poverty, literacy, language, culture and social isolation. directing patients to needed supportive care services is even more difficult than providing them with appropriate technical care. a large proportion of the population do not have equitable access to services and face major problems navigating complex systems. new approaches are needed to bridge across diverse populations and reach out to underserved patients most in need. the objective of this project was to develop an innovative program to help underserved cancer patients access, understand and use needed health and social services. it implemented and evaluated, a pilot intervention employing trained 'personal health coaches' to assist underserved patients from a variety of ethno-linguistic, socio economic and educational backgrounds to meet their supportive cancer care needs. the intervention was tested with a group of underserved cancer patients at the princess margaret hospital, toronto. personal coaches helped patients identify needs, access information, and use supportive care services. triangulation was used to compare and contrast multiple sources of quantitative and qualitative evaluation data provided by patients, personal health coaches, and health care providers to assess needs, barriers and the effectiveness of the coach program. many patients faced multiple barriers and had complex unmet needs. barriers of poverty and language were the easiest to detect. a formal, systematic method to identify and meet supportive care needs was not in place at the hospital. however, when patients were referred to the program, an overwhelming majority of participants were highly satisfied with the intervention. the service also appeared to have important implications for improved technical health care by ensuring attendance at appointments, arranging transportation and translation services, encouraging adherence to therapy and mitigating financial hardship -using existing community services. this intervention identified a new approach that was effective in helping very needy patients navigate health and social services systems. such programs hold potential to improve both emotional and physical health out· comes. since assistance from a coach at the right time can prevent crises, it can create efficiencies in the health system. the successful use of individuals who were not licensed health professionals for this purpose has implications for health manpower planning. needle exchange programs (neps) have been distributing harm reduction materials in toronto since . counterfit harm reduction program is a small project operated out of a community health centre in south-east toronto. the project is operated by a single full-time coordinator, one pan-rime mobile outreach worker and two peers who work a few hours each week. all of counterfit's staff, peers, and volunteers identify themselves as active illicit drug users. yet the program dis~rib utes more needles and safer crack using kits and serves more illicit drug u~rs t~an the comb ~e~ number of all neps in toronto. this presentation will discuss the reasons behind this success, .s~ f cally the extended hours of operation, delivery models, and the inclusion of an. extremely marg ~ahzed community in all aspects of program design, implementation and eva.luat ?n. ~ounterfit was recently evaluated by drs. peggy milson and carol strike, two leading ep dem olog st and researchers in the hiv and nep fields in toronto and below are some of their findings: "the program has experienced considerable success in delivering a high quality, accessible and well-used program .... the pro· gram has allowed (service users) to become active participants in providing. services to others and has resulted in true community development in the best sense. " ... counterf t has ~~n verr succe~sful attracting and retaining clients, developing an effective peer-based model an.d assisting chen~s ~ th a vast range of issues .... the program has become a model for harm red~ctmn progr~ms withm the province of ontario and beyond." in june , the association of ?ntano co~mumty heal~~ <:en· ires recognized counterfit's acheivements with the excellence m community health initiatives award. in kenya, health outcomes and the performance of government health service~ have det~riorated since the late s, trends which coincide with a period of severe resource constramts necessitated by macro-economic stabilization measures after the extreme neo-liberalism of the s. when the govern· ment withdrew from direct service provision as reform trends and donor advocacy suggested, how does it perform its new indirect role of managing relations with new direct health services providers in terms of regulating, enabling, and managing relations with these health services providers? in this paper therefore, we seek to investigate how healthcare access and availability in the slums of nairobi has been impacted upon by the government's withdrawal from direct health care provision. the methodology involved col· leering primary data by conducting field visits to health institutions located in the slum areas of kibera and korogocho in nairobi. purposive random sampling was utilized in this study because this sampling technique allowed the researcher(s) to select those health care seekers and providers who had the required information with respect to the objectives of the study. in-depth interviews using a semi-structured ques· tionnaire were administered ro key informants in health care institutions. this sought to explore ways in which the government and the private sector had responded and addressed in practical terms to new demands of health care provision following the structural adjustment programmes of the s. this was complemented by secondary literature review of publications and records of key governmental, bilateral and multilateral development partners in nairobi. the study notes a number of weaknesses especially of kenya's ministry of health to perform its expected roles such as managing user fee revenue and financial sustainability of health insurance systems. this changing face of health services provision in kenya there· fore creates a complex situation, which demands greater understanding of the roles of competition and choice, regulatory structures and models of financing in shaving the evolution of health services. we rec· ommend that the introduction of user fees, decentralization of service provision and contracting-out of non-clinical to private and voluntary agencies require a new management culture, and new and clear insri· tutional relationships. experience with private sector involvement in health projects underlines the need not only for innovative financial structures to deal with a multitude of contractual, political, market and risks, but also building credible structures to ensure that health services projects are environmentally responsive, socially sensitive, economically viable, and politically feasible. purpose: the purpose of this study is to examine the status of mammography screening utilization and its predictors among muslim women living in southern california. methods: we conducted a cross-sectional study that included women aged ::!: years. we col· leered data using a questionnaire in the primary language of the subjects. the questionnaire included questions on demography; practices of breast self-examination (bse) and clinical breast examination (cbe); utilization of mammography; and family history of breast cancer. bivariate and multiple logistic regression analyses were performed to estimate the odds ratios of mammography use as a function of demographic and other predictor variables. . results: among the women, % were married, % were - years old, and % had family h story of breast cancer. thirty-two percent of the participating women never practiced bse and % had not undergone cbe during the past two years. the data indicated that % of the women did not have mammography in the last two years. logistic regression analysis showed that age ( r= . , % confi· dcnc~ interval (cl)=l. - . ), having clinical breast examination ( r= . , % cl= . - . ), and practtce of self-breast examination ( r= . , % cl= . - . ), were strong predictors of mammography use . . conclusions: the data point to the need for intervention targeting muslim women to inform and motivate th.cm a~ut practices for early detection of breast cancer and screening. further studies are needed to investigate the factors associated with low utilization of mammography among muslim women population in california. we conducted a review of the scientific literature and° government documents to describe ditnational health care program "barrio adentro" (inside the neighborhood). we also conducted qualiurivt interviews with members of the local health committees in urban settings to descrihe the comm unity participation component of the program. rtsmlts: until recently, the venezuelan public health system was characterized by a lack or limited access w health care ( % of the population) and long waiting lists that amounted to denial of service. moit than half of the mds worked in the five wealthiest metropolitan areas of the country. jn the spring oi , a pilot program hired cuban mds to live in the slums of caracas to provide health care to piople who had previously been marginalized from social programs. the program underwent a massive expansion and in only two years , cuban and , venezuelan health care providers were working acmss the country. they provide a daily average of - medical consultations and home visits, c lly out neighborhood rounds, and deliver health prevention initiatives, including immunization programs. they also provide generic medicines at no cost to patients, which treat % of presenting ill-ij!m, barrio adentro aims to build , clinics (primary care), , diagnostic and rehabilitation ctnrres (secondary care), and upgrade the current hospital infrastructure (tertiary care). local health committees survey the community to identify needs and organize a variety of lobby groups to improve dit material conditions of the community. last year, barrio adentro conducted . times the medical visits conducted by the ministry of health. the philosophy of care follows an integrated approach where btalrh is related to housing, education, employment, sports, environment, and food security. conclusions: barrio adentro is a unique collaboration between low-middle income countries to provide health care to people who have been traditionally excluded from social programs. this program shows that it is possible to develop an effective international collaboration based on participatory democracy. low-income americans are at the greatest risk of being uninsured and often face multiple health concerns. this evaluation of the neighborhood health initiative (nh!), an organization which uses multiple programmatic approaches to meet the multiple health needs of clients, reflected the program's many activities and the clients' many service needs. nh! serves low-income, underserved, and hard-to-reach residents in the des moines enterprise community. multiple approaches (fourth-generation evaluation, grounded theory, strengths-and needs-based) and methods (staff and client interviews, concept mapping, observations, qualitative and quantitative analysis) were used to achieve that reflection. results indicate good targeting of residents in the zip code and positive findings in the way of health insurance coverage and reported unmet health needs of clients. program activities were found to match client nttds, validating the organization\'s assessment of clients. important components of nhi were the staff composition and that the organization had become part of both the formal and informal networks. nhi positioned as a link between the target population and local health and social sc:rvice agencies, working to connect residents with services and information as well as aid local agencies in reaching this underserved population. p - (c) welfare: definition by new york city maribeth gregory for an individual who resides in new york city, to obtain health insurance under the medicaid policy one must fall under certain criteria .. (new york city's welfare programs ) if the individual _is on ssi or earns equal to or less than $ per month, he is entitled to receive no more than $ , m resources. a family the size of two would need to earn less than $ per month to qualify for no greater than ss, worth of medicaid benefits. a family of three would qualify for $ , is they earned less than $ per month and so on. introduction: the vancouver gay communiry has a significant number of asian descendan!l. because of their double minority status of being gay and asian, many asian men who have sex with men (msm) are struggling with unique issues. dealing with racism in both mainstream society and the gay communiry, cultural differences, traditional family relations, and language challenges can be some of their everyday srruggles. however, culturally, sexually, and linguistically specific services for asian msm are very limited. a lack of availability and accessibiliry of culturally appropriate sexual health services isolates asian msm from mainstream society, the gay community, and their own cultural communities, deprives them of self-esteem, and endangers their sexual well-being. this research focuses on the qualita· tive narrative voices of asian msm who express their issues related to their sexualiry and the challenges of asking for help. by listening to their voices, practitioners can get ideas of what we are missing and how we need to intervene in order to reach asian msm and ensure their sexual health. methods: since many asian msm are very discreet, it is crucial to build up trust relationships between the researcher and asian msm in order to collect qualitative data. for this reason, a community based participatory research model was adopted by forming a six week discussion group for asian msm. in each group session, the researcher tape recorded the discussion, observed interactions among the participants, and analyzed the data by focusing on participants' personal thoughts, experiences, and emotions for given discussion topics. ra lts: many asian msm share challenges such as coping with a language barrier, cultural differ· ences for interpreting issues and problems, and westerncentrism when they approach existing sexual health services. moreover, because of their fear of being disclosed in their small ethnic communities, a lot of asian msm feel insecure about seeking sexual health services when their issues are related to their sexual orientation. conclflsion: sexual health services should contain multilingual and multicultural capacities to meet minority clients' needs. for asian msm, outreach may be a more effective way to provide them with accessible sexual health services since many asian msm are closeted and are therefore reluctant to approach the services. building a communiry for asian msm is also a significant step toward including them in healthcare services. a communiry-based panicipatory approach can help to build a community for asian msm since it creates a rrust relationship between a worker and clients. p - (c) identifying key techniques to sustain interpretation services for assisting newcomers isolated by linguistic and cultural barriers from accessing health services s. gopi krishna lntrodaetion: the greater toronto area (gta) is home to many newcomer immigrants and other vulnerable groups who can't access health resources due to linguistic, cultural and systemic barriers. linguistic and cultural issues are of special concern to suburbs like scarborough, which is home to thousands of newcomer immigrants and refugees lacking fluency in english. multilingual community ~nterpreter. service~ (mcis) is a non-profit social service organization mandated to provide high quality mterpretanon services. to help newcomers access health services, mcis partnered with the scarborough network of immigrant serving organizations (sniso) to recruit and train volunteer interpreters to accompany clienrs lacking fluency in english and interpret for them to access health services at various locati?ns, incl~~ing communiry ~c:-lth centres/social service agencies and hospitals. the model envisioned agencies recruin~ and mcis ~.mm.g and creating an online database of pooled interpreter resources. this da.tabase, acces& bl~ to all pama~~g ?rganization is to be maintained through administrative/member · ship fees to. be ~ d by each parnapanng organization. this paper analyzes the results of the project, defines and identifies suc:cases before providing a detailed analysis for the reasons for the success . . methods:. this ~per~ q~ntitative (i.e. client numben) and qualitative analysis (i.e. results of key •~ormant m~rv ews with semce ~sers and interpreters) to analyze the project development, training and mplementanon phases of the project. it then identifies the successes and failures through the afore· mentioned analysis. poster sessions vss resljts: the results of the analysis can be summarized as: • the program saw modest success both ia l?lllls of numbers of clients served as well as sustainability at various locations, except in the hospital iririog. o the success of the program rests strongly on the commitment of not just the volunteer interprmr, but on service users acknowledgments through providing transponation allowance, small honororia, letter of reference etc. • the hospital sustained the program better at the hospital due to the iolume and nature of the need, as well as innate capacity for managing and acknowledging volunceers. collc/llsion: it is possible to facilitate and sustain vulnerable newcomer immigrants access to health !ul'ices through the training and commitment of an interpreter volunteer core. acknowledging volunteer commitment is key to the sustenance of the project. this finding is important to immigration and health policy given the significant numbers of newcomer immigrants arriving in canada's urban communities. nity program was established in to provide support to people dying at home, especially those who were waiting for admission to the resi<lential hospice. with the advent of haart and corresponding challenges for people living with hiv/aids in the community, the community program has developed a unique case management approach. this model features an interdisciplinary team providing a clientdrivcn service. the case manager provides continuity of care to clients in a variety of settings both within and outside of the health care system. a case study is used to demonstrate how formal and informal networks of support facilitate efficient and appropriate resource utilization to promote client health. this case study demonstrates the value of consistent coordination with a client who has complex physical, spiritual, substance use and mental health needs. the authors will show how they liaised with the housing authority, police, social services as well as the family physician, clinic staff and a hospital emergtncy room to ensure this client did not fall between the cracks. tarek hussain recognition of the importance of community involvement and sectoral cooperation in health and !ocial services, formalized in alma-ata declaration in , was reinforced at riga meeting held at the mid·point between alma-ata and the year . then at the th anniversary of alma-ata declaration, ir was declared that 'primary health care is everybody's business'. health does not exist in isolation. health cannot be defined only as an outcome of 'medical care' but also as one of 'social action'; the responsibility of disease prevention and health promotion rests not only on governments, but also with don·govemmentorgan izations, the community, and individuals. the major accomplishment to date may be that rhere is growing realization in the health sector that community involvement is more than a political right-it is absolute necessary. lessons have learned during the implementation of disease-specific l'cltical programmes, such as cdd, ari, and epi; first, integrated and holistic approaches to childcare art needed, and second, the need for community involvement has become evident. imc! is a broad inte-gra ed strategy with an overall objective contributing to reducing child morbidity and mortality in developing countries. and one of the imci components, 'community !mci', which is now broadening ~s an entry point for child-focused community development initiatives. community jmcl/c~ ld health is ~n mtcgrated approach to the promotion of key family and community practices that have impact on: child growth and development, disease prevention, home care for sick, malnourished child~en, a.nd care-seekmg behavior and compliance with advice and treatment. the presentation addres~es, m brief, the ~evel opinent of community !mci, operational aspect of community/im cl, key strategies and tools ava la~le for implementation of c/imci. the paper draws some successful programme examples on working logether for imc! with the community in various countries which had substantial benefns on programme outcomes. p - t (c) healthy child screening: an innovative service initiative ann-marie marcolin and joyce allen . introduction: with mounting attention for creative and integrated models of c~re .that are populallon and community focused, the healthy child screening initiative achiev.es t~ese pnncipl~s and more! . • parkdale high park rotary (sponsorship) the heal~h ~h ld scree? ?g is a ~opl~-centred model of care. agency and professional sector-specific silos are ehmmated, ~rov dmg f~~ hes wit~ one-sto~ access to primary prevention services in a local school gym! children at nsk are rece vmg early mtervent n and appropriate referrals to the right care provider, at the right time a~d in t~e right place. further, with a complimentary focus on prevention, the program serves to keep at nsk children healthy. healthy child screening results: the service model is developed around four distinct phases: ) planned outreach; ) coordinated intake and registration; ) interdisciplinary screening; and ) targeted referral. since the fall and through six collaborative healthy child screenings children ranging in age from to have benefited from this unique service model of care. conclusion: the presentation will provide practical information on the development and implementation of the model. there will also be a focus on lessons learned in building community service provider-hospital relationships. according to statistics canada ( ) % of the toronto population was born outside of canada and % were new immigrants. immigrants often arrive in canada in superior health compared to the canadian born population, but they lose this health advantage over time. changes in immigrant health status over time may be attributed to a variety of factors including barriers to accessing and receiving care as well as limitations in the mainstream health service organizations and their approaches to health care delivery (hyman, ) . for example, immigrant women are less likely to receive pap tests, which places them at a greater risk for developing cervical cancer. similarly, immigrant women receive less mammography screening than their canadian counterparts. the immigrant women's health centre mobile health unit (mhu) was created as an alternative care delivery model to address the need for increased accessibility as well as culturally and linguistically appropriate reproductive health care. toronto western hospital and the immigrant women's health centre have formed a collaborative partnership which incorporates a primary care nurse practitioner and lay ethnocultural counselors providing care on the mhu. currently, a qualitative ethnonursing study is underway to understand the unique experiences of women using the mhu for their reproductive health care as well as the perspectives of the mhu health care providers. based on a literature review and preliminary findings from provider and participant interviews, the proposed presentation will address the themes of health status for immigrant and refugee women, accessibility issues as well strategies to improve their reproductive health care. we will discuss benefits as well as limitations to health care provision using this alternative service delivery model. michael carden, brian edlin, andrew talal, elizabeth getter, and marla shu lntrod.ction: to date most active drug users have not had access to treatment for hepatitis c virus (hcv) infection and substantial barriers continue to exist that interfere with treatment availability for this population. methods: active illicit drug users interested in pursuing hcv care and treatment were recruited in partnership w~th co~munity-based organizations (cbo's) in new york city. baseline data were collected on quahty of hfe, substance use patterns, depression, health care utilization, hcv health beliefs and other relev.ant variables. medical evaluations were conducted, including liver biopsy when indicated, an~ treatment ts ~ffered when no contraindications are present. participants also receive psychiatric evaluahons to determme the appropriateness of interferon treatment. renlts: fifteen individuals have been recruited to date and received an initial medical evaluation. the mean age was years and _the average age of initial heroin or cocaine use was . . eight ( %) ha~ been homeless at least once m the last months and s ( %) were homeless for most or all of this penod. fourteen ( %) had a history of injection drug use with the mean age at first injection being s frsewons v ,an. elrven persc.!ns ( %) reported inje~~ng .heroin or cocaine within the last days while the .wing four ( l'o) reported regular non-m ect on use of cocaine and street-obtained benzodiazepines. sijiy seven percent of the sample (n= ) reported ever being referred to hcv treatment while ( t % ) ftponeddiattreann~nt had been offered by~ ~e.dical provider. none had ever received a liver biopsy or araanent. most believed that hcv was a s gmf cant threat to their health ( %) and that there was a pm)dchance they would eventually die if their hepatitis c was not treated ( %). though individuals % believed that there was no cure for hcv, ( %) reported that they would initiate treatment if i was recommended by their doctor. thirteen ( %) had a current psychiatric diagnosis including «pmsion, anxiety disorder, schizophrenia, schizoaffective disorder, and borderline and antisocial persooaliry disorders. among eight individuals who had the beck depression inventory administered, the mean score was . . attendance rates were % ( / ) at scheduled medical and psychiatric ppointments and % ( / ) at liver biopsy. <andtuions: active drug users, despite experiencing multiple psycho-social problems, can be mgaged in hcv care using a multidisciplinary approach, but require intensive follow-up support. hcv aunnent of active drug users should not be dismissed. n- (c) antiretroviral therapy in mv infected infants: when to initiate therapy an african experience kingsley okonkwo, ademola adeyemo, israel sokeye, and nwaife umeike /""°""ction: as technology for early diagnosis of human immunodeficiency virus [hiv] improves, m to commence highly active antiretroviral therapy [haarn is yet to be fully evaluated. this prospective study describes our initial experience with early haart in hiv infected nigerian infants and rqions the outcome. we also analyzed the socioeconomic implications of early haart therapy in infants in the african setting. method: hiv infected infants were started on haart before months and followed up at mkly intervals.we monitored baseline and monthly cd . conclusion: initial results suggest early haart before months resulted. in improv~d out~ome in african children. treatment appears to be as effective as in developed counmes. in. a~nca as. m most developing countries with limited resources it is possible and effective to use haart m ~~ants if p~oper llloniroring facilities are available. however the occurrence of long-term drug related tox c ty and mk of emergence of resistant viral strains create need for further evaluation of haart in infants. background: most risk factors for cardiovascular disease (cvd) can be mitigated through ~th clinical interventions and lifestyle change. we used data from a telephone survey of new york city (nyc) adults to characterize health care access and healthy behavior among those with three or more cvd risk factors. methods: the study population included respondents to the nyc community health survey (n= , ) self-reporting~ of the following: smoking, diabetes, high cholesterol level, high blood pres· sure, body mass index > , and age > (males) or > (females) (n= , ). results: based on self-report, an estimated . , ( %) of nyc adults have~ or more cvd risk factors. this population is % male, % white, % black, and % with s years of education. most report good access to health care, indicated by having health insurance ( %), regular doctor ( %), their blood pressure checked within last months ( %), and their choles· terol checked within the past year ( % ). only % reported getting at least minutes of exercise ~ times per week and only % eating ~ servings of fruits and vegetables the previous day. among current smokers, % attempted to quit in past months, but only % used medication or counseling. implications: these data suggest that most nyc adults known to be at high risk for cvd have access to regular health care, but most do not engage in healthy lifestyle or, if they smoke, attempt effective quit strategies. more clinic-based and population-level interventions are needed to support lifestyle change among those at high risk of cvd. introduction: recently, much interest has been directed at "obesogenic" (obesity-promoting) (swinburn, egger & raza, ) built environments, and at geographic information systems (gis) as a tool for their exploration. a major geographical concept is accessibility, or the ease of moving from an origin to a destination point, which has been recently explored in several health promotion-related stud· ies. there are several methods of calculating accessibility to an urban feature, each with its own strengths, drawbacks and level of precision that can be applied to various health promotion research issues. the purpose of this paper is to describe, compare and contrast four common methods of calculating accessibility to urban amenities in terms of their utility to obesity-related health promotion research. practical and conceptual issues surrounding these methods are introduced and discussed with the intent of providing health promotion researchers with information useful for selecting the most appropria e accessibility method for their research goal~ ~ethod: this paper describes methodological insights from two studies, both of which assessed the neighbourhood-level accessibility of fast-food establishments in edmonton, canada -one which used a relatively simple coverage method and one which used a more complex minimum cos method. res.its: both methods of calculating accessibility revealed similar patterns of high and low access to fast-food outlets. however, a major drawback of both methods is that they assume the characteristics of the a~e~ities and of the populations using them are all the same, and are static. the gravity potential method is introduced as an alternative, since it is ·capable of factoring in measures of quality and choice. a n~mber of conceptual and pr~ctical iss~es, illustrated by the example of situational influences on food choice, make the use of the gravity potential model unwieldy for health promotion research into sociallydetermined conditions such as obesity. co.nclusions: i~ ~ommended that geographical approaches be used in partnership with, or as a foun~ation for, ~admonal exploratory methodologies such as group interviews or other forms of commumty consultation that are more inclusive and representative of the populations of interest. qilhl in los angeles county ,,..ia shaheen, richard casey, fernando cardenas, holman arthurs, and richard baker ~the retinomax autorefractor has been used for vision screening of preschool age childien. ir bas been suggested to be used and test school age children but not been validated in this age poup. ob;taiw: to compare the results of retinomax autorefractor with findings from a comprehensive i!' examination using wet retinoscopy for refractive error. mllhods: children - years old recruited from elementary schools at los angeles county were iaml with snellen's chart and the retinomax autorefractor and bad comprehensive eye examination with dilation. the proportion of children with abnormal eye examination as well as diesensitiviry and specificity of the screening tools using retinomax autorefractor alone and in combinalion wirh snellen's chart. results of the children enrolled in the study (average age= . ± . years; age range, - years), ?% had abnormal eye examination using retinoscopy with dilation. for the lerinomax, the sensitivity was % ( % confidence interval [ci] %- %), and the specificity was % ( % ci, %- o/o). simultaneous testing using snellen's chart and retinomax resulted in gain in sitiviry ( %, % cl= , ), and loss in specificity ( %, % cl= %- %). the study showed that screening school age children with retinomax autorefractor could identify most cases with abnormal vision but would be associated with many false-positive results. simuhaneous resting using snellen's chart and retinomax maximize the case finding but with very low specificiry. mdhotjs: a language-stratified, random sample of members of the college of family physicians of canada received a confidential survey. the questionnaire collected data on socio-demographic characteristics, medical training, practice type, setting and hcv-related care practices. the self-adminisratd questionnaire was also made available to participants for completion on the internet. batdti: response proportion was %. median age was years ( % female) and the proporlionoffrench questionnaires was %. approximately % had completed family medicine residency lllining in canada; median year of training completion was . sixty-seven percent, % and % work in private offices/clinics, community hospitals and emergency departments, respectively. regarding ~practices, % had ever requested a hcv test and % of physicians had screened for hcv iafrction in rhe past months· median number of tests was . while % reported having no hcv-uaed patients in their practic~, % had - hcv-infected patients. regarding the level of hcv care provided, . % provide ongoing advanced hcv care including treatment and dose monitoring for ctmduions: in this sample of canadian family physicians, most had pro~ided hcv screening. to •least one patient in the past year. less than half had - hcv-infected patients and % provide ~:relared care the role of socio-demographic factors, medical training as wel_i as hcv ca~e percep-lldas rhe provision of appropriate hcv screening will be examined and described at the time of the canference. ' - (c) healthcare services: the context of nepal meen poudyal chhetri """ tl.ction healthcare service is related with the human rights and fundamental righ~ of the ci~ ciaaiuntry. however, the growing demand foi health care services, quality heal~care service, accessib b~ id die mass population and paucity of funds are the different but interrelated issues to .be ~ddressed. m nepat. n view of this context, public health sector in nepal is among other sectors, which is struggling -.i for scarce resources. . . . nepal, the problems in the field of healthcare servic~s do not bnut ~o the. paucity of faads and resources only, but there are other problems like: rural -urban imbalance, regional unbalance, poster sessio~ f the ll ·m ·ted resources poor healthcare services, inequity and inaccessibility of the poor management o , . poor people of the rural, remote and hilly areas for the healthcare services and so on.. . . . · . i f ct the best resource allocation is the one that max m zes t e sum o m ivi ua s u · ea t services. n a , · h d' ·b · · · h . ·t effi.ciency and efficient management are correlated. it might be t e re istn utmn of mes. ence, equi y, . . . . . income or redistribution of services. moreover, maximizanon of available resources, qua tty healthcare services and efficient management of them are the very important and necessary tools and techmques to meet the growing demand and quality healthcare services in nepal. p - (a) an jn-depth analysis of medical detox clients to assist in evidence based decision making xin li, huiying sun, ajay puri, david marsh, and aslam anis introduction: problematic substance use represents an ever-increasing public health challenge. in the vancouver coastal health (vch) region, there are more than , individuals having some probability of drug or alcohol dependence. to accommodate this potential demand for addiction related services, vch provides various services and treatment, including four levels of withdrawal management services (wms). clients seeking wms are screened and referred to appropriate services through a central telephone intake service (access i). the present study seeks to rigorously evaluate one of the services, vancouver detox, a medically monitored -bed residential detox facility, and its clients. doing so will allow decision makers to utilize evidence based decision-making in order to improve the accessibility and efficiency of wms, and therefore, the health of these clients. methods: we extract one-year data (october , -september , from an efficient and comprehensive database. the occupancy rate of the detox centre along with the clients' wait time for service and length of stay (los) are calculated. in addition, the effect of seasonality on these variables and the impact of the once per month welfare check issuance on the occupancy rate are also evaluated. results: among the clients (median age , % male) who were referred by access! to vancouver detox over the one-year period, were admitted. the majority ( %) of those who are not admitted are either lost to follow up (i.e., clients not having a fixed address or telephone) or declined service at time of callback. the median wait time was day [q -ql: - ], the median los was days iq -qt: - ], and the average bed occupancy rate was %. however, during the threeday welfare check issue period the occupancy rate was lower compared to the other days of the year % vs. %, p conclusion: our analysis indicates that there was a relatively short wait time at vancouver detox, however % of the potential clients were not served. in addition, the occupancy rate declined during the welfare check issuance period and during the summer. this suggests that accessibility and efficiency at vancouver detox could be improved by specifically addressing these factors. background: intimate partner violence (ipv) is associated with acute and chronic physical and men· tal health outcomes for women resulting in greater use of health services. yet, a vast literature attests to cultural variations in perceptions of health and help-seeking behaviour. fewer studies have examined differences in perceptions of ipv among women from ethnocultural communities. the recognition, definition, and understanding of ipv, as well as the language used to describe these experiences, may be different in these communities. as such, a woman's response, including whether or not to disclose or seek help, may vary according to her understanding of the problem. methods: this pilot study explores the influence of cultural factors on perceptions of and responses to ipv among canadian born and immigrant young women. in-depth focus group interviews were con· ducted with women, aged to years, living in toronto. open-ended and semi-structured interview questions were designed to elicit information regarding how young women socially construct jpv and where they would go to receive help. interviews were transcribed, then read and independently coded by the research team. codes were compared and disagreements resolved. qualitative software qsr n was used to assist with data management. . ruu~ts_: res~nses_abo~t what constitutes ipv were similar across the study groups. when considering specific ab.us ve ~ tuanons and types of relationships, participants held fairly relativistic views about ipv, especially with regard to help-seeking behaviour. cultural differences in beliefs about normaive m;ile/femal~ relations. familial.roles, and customs governing acceptable behaviours influenced partictpants perceptions about what n ght be helpful to abused women. interview data highlight the social l ter srnfons v suucrural _impact these factors ha:e on you?g women and provide details regarding the dynamics of cibnocultur~ m~uences on help-~eekmg behav ur: t~e ro~e of such factors such as gender inequality within rtlaoo?sh ps and t_he ~erce ved degree of ~oc al solat on and support nerworks are highlighted. collc~ the~ findmgs unde~score the _ mporta_nc_e of understanding cultural variations in percrprions of ipv ~ relanon to ~elp-seekmg beha~ ':'ur. th s_mformation is critical for health professionals iodiey may connnue developmg culturally sensmve practices, including screening guidelines and protorol s. ln addition, _this study demonstr~tes that focus group interviews are valuable for engaging young romen in discussions about ipv, helpmg them to 'name' their experiences, and consider sources of help when warranted. p -s (a) health problems and health care use of young drug users in amsterdam .wieke krol, evelien van geffen, angela buchholz, esther welp, erik van ameijden, and maria prins / trod ction: recent advances in health care and drug treatment have improved the health of populations with special social and health care needs, such as drug users. however, still a substantial number dots not have access to the type of services required to improve their health status. in the netherlands, tspccially young adult drug users (yad) whose primary drug is cocaine might have limited access to drugrreatment services. in this study we examined the history and current use of (drug associated) treatmmt services, the determinants for loss of contact, and the current health care needs in the young drug mm amsterdam study (yodam). methods: yodam started in and is embedded in the amsterdam cohort study among drug mm. data were derived from y ad aged < years who had used cocaine, heroin, ampheramines and i or methadone at least days a week during the months prior to enrolment. res lts:of yao, median age was years (range: - years), % was male and % had dutch nationality at enrolment. nearly all participants ( %) reported a history of contact with drug llt.lnnent services (methadone maintenance, rehabilitation clinics and judicial treatment), mental health car? (ambulant mental care and psychiatric hospital) or general treatment services (day-care, night-care, hdp for living arrangements, work and finance). however, only % reported contact in the past six l!xlllths. this figure was similar in the first and second follow-up visit. among y ad who reported no current contact with the health care system, % would like to have contact with general treatment serl' icts. among participants who have never had contact with drug treatment services, % used primarily cocaine compared with % and % among those who reported past or current contact, respectively. saied on the addiction severity index, % reported at least one mental health problem in the past days, but only % had current contact with mental health services. concl sion: results from this study among young adult drug users show that despite a high contact rm with health care providers, the health care system seems to lose contact with yao. since % indicatt the need of general treatment services, especially for arranging house and living conditions, health m services that effectively integrate general health care with drug treatment services and mental health care might be more successful to keep contact with young cocaine users. mtthods: respondents included adults aged and over who met dsm-iv diagn?snc criteria for an anxiety or depressive disorder in the past months. we performed two sets of logisnc regressmns. thtdichotomous dependent variables for each of the regressions indicated whether rhe respondenr_vis-ud a psychiatrist, psychologist, family physician or social worker in the _past_ months. no relationship for income. there was no significant interaction between educatmn an mco~:· r: ::or respondents with at least a high school education to seek help ~rom any of the four servic p were almost twice that for respondents who had not completed high school. th . d ec of analyses found che associacion becween educacion and use of md-provided care e secon s · · be d · · ·f· ly ·n che low income group for non-md care, the assoc anon cween e ucatlon and was s gm icant on -· . . . . use of social workers was significant in both income groups, but significant only for use of psychologists in che high-income group. . . . conclusion: we found differences in healch service use by education level. ind v duals who have nor compleced high school appeared co use less mental he~lt~ servi~es provided ~y psyc~iatrists, psycholo· gists, family physicians and social workers. we found limited e.v dence _suggesting the influence of educa· tion on service use varies according to income and type of service provider. results suggesc there may be a need to develop and evaluate progr~ms.designe~ to deliver targeted services to consumers who have noc completed high school. further quahtanve studies about the expen· ence of individuals with low education are needed to clarify whether education's relationship with ser· vice use is provider or consumer driven, and to disentangle the interrelated influences of income and education. system for homeless, hiv-infected patients in nyc? nancy sahler, chinazo cunningham, and kathryn anastos introduction: racial/ethnic disparities in access to health care have been consistently documented. one potential reason for disparities is that the cultural distance between minority patients and their providers discourage chese patients from seeking and continuing care. many institucions have incorporated cultural compecency craining and culturally sensicive models of health care delivery, hoping co encourage better relacionships becween patients and providers, more posicive views about the health care system, and, ulcimacely, improved health outcomes for minority patients. the current scudy tests whether cultural distance between physicians and patients, measured by racial discordance, predicts poorer patient attitudes about their providers and the health care system in a severely disadvantaged hiv-infected population in new york city that typically reports inconsistent patterns of health care. methods: we collected data from unscably housed black and latino/a people with hiv who reported having a regular health care provider. we asked them to report on their attitudes about their provider and the health care system using validated instruments. subjects were categorized as being racially "concordant" or "discordant" with their providers, and attitudes of these two groups were compared. results: the sample consisted of ( %) black and ( %) latino/a people, who reported having ( %) black physicians, ( %) latino/a physicians, ( %) white physicians, and ( %) physicians of another/unknown race/ethnicity. overall, ( %) subjects had physicians of a different race/ethnicity than their own. racial discordance did not predict negative attitudes about rela· tionship with providers: the mean rating of a i-item trust in provider scale (lo=high and o=low) was . for both concordant and discordant groups, and the mean score in -icem relationship with provider scale ( =high and !=low) was . for both groups. however discordance was significantly associated with distrust in che health care syscem: che mean score on a -icem scale ( =high discrust and l=low distrust) was . for discordant group and . for che concordant group (t= . , p= . ). we further explored these patterns separacely in black and lacino/a subgroups, and using different strategies ro conceptualize racial/ethic discordance. conclusions: in this sample of unscably housed black and latino/a people who receive hiv care in new york city, having a physician from the same racial/ethnic background may be less important for developing a positive doctor-patient relationship than for helping the patients to dispel fear and distrust about the health care system as a whole. we discuss the policy implications of these findings. ilene hyman and samuel noh . .abstract objectiw: this study examines patterns of mental healthcare utilization among ethiopian mm grants living in toronto. methods: a probability sample of ethiopian adults ( years and older) completed structured face-to-face interviews. variables ... define, especially who are non-health care providers. plan of analysis. results: approximately % of respondents received memal health services from mainstream healthcare providers and % consulted non-healthcare professionals. of those who sought mental health services from mainstream healthcare providers, . % saw family physicians, . % visited a psychiatrist. and . % consulted other healthcare providers. compared with males, a significantly higher proportion gsfer sessions v ri ftlnales consulted non-healthcare_ professionals for emotional or mental health problems (p< . ). tlbile ethiopian's overall use of mamstream healthcare services for emotional problems ( %) did not prlydiffer from the rate ( %) of the general population of ontario, only a small proportion ( . %) rjerhiopians with mental health needs used services from mainstream healthcare providers. of these, !oj% received family physicians' services, . % visited a psychiatrist, and . % consulted other healthll/c providers. our data also suggested that ethiopian immigrants were more likely to consult tradioooal healers than health professionals for emotional or mental health problems ( . % vs. . % ). our bivariate analyses found the number of somatic symptoms and stressful life events to be associated with an increased use of medical services and the presence of a mental disorder to be associated with a dfcreased use of medical services for emotional problems. however, using multivariate methods, only die number of somatic symptoms remained significantly associated with use of medical services for emooonal problems. diu#ssion: study findings suggest that there is a need for ethnic-specific and culturally-appropriate mrcrvention programs to help ethiopian immigrants and refugees with mental health needs. since there ~a strong association between somatic symptoms and the use family physicians' services, there appears robe a critical role for community-based family physicians to detect potential mental health problems among their ethiopian patients, and to provide appropriate treatment and/or referral. the authors acknowledge the centre of excellence for research in immigration and settlement (ceris) in toronto and canadian heritage who provided funding for the study. we also acknowledge linn clark whose editorial work has improved significantly the quality of this manuscript. we want to thank all the participants of the study, and the ethiopian community leaders without whose honest contributions the present study would have not been possible. this paper addresses the impact of the rationalization of health-care services on the clinical decision-making of emergency physicians in two urban hospital emergency departments in atlantic canada. using the combined strategies of observational analysis and in-depth interviewing, this study provides a qualitative understanding of how physicians and, by extension, patients are impacred by the increasing ancmpts to make health-care both more efficient and cost-effective. such attempts have resulted in significantly compromised access to primary care within the community. as a consequence, patients are, out of necessity, inappropriately relying upon emergency departments for primary care services as well as access to specialty services. within the hospital, rationalization has resulted in bed closures and severely rmricted access to in-patient services. emergency physicians and their patients are in a tenuous position having many needs but few resources. furthermore, in response to demands for greater accountability, physicians have also adopted rationality in the form of evidence-based medicine. ultimately, ho~ever, rationality whether imposed upon, or adopted by, the profession significantly undermines physu.: ans' ability to make decisions in the best interests of their patients. johnjasek, gretchen van wye, and bonnie kerker introduction: hispanics comprise an increasing proportion of th.e new york city (nyc) populanon !currently about %). like males in the general population, h spamc males (hm) have a lower prrval,nce of healthcare utilization than females. however, they face additional access barriers such as bnguage differences and high rates of uninsurance. they also bear a heavy burden of health problems lllehasobesity and hiv/aids. this paper examines patterns of healthcare access and ut hzat on by hm compared to other nyc adults and identifies key areas for intervention. . . . and older are significantly lower than the nhm popu anon . v. . , p<. ), though hi\' screening and immunizations are comparable between the two groups. conclusion: findings suggest that hm have less access t? healthcare than hf or nhm. hown r, hm ble to obtain certain discrete medical services as easily as other groups, perhapsdueto!rtor are a hm. i i . subsidized programs. for other services, utilization among s ower. mprovmg acc~tocareinthis group will help ensure routine, quality care, which can lead to a greater use of prevennve services iii! thus bener health outcomes. introduction: cancer registry is considered as one of the most important issues in cancer epidemiology and prevention. bias or under-reporting of cancer cases can affect the accuracy of the results of epidemiological studies and control programs. the aim of this study was to assess the reliability of the regional cancer report in a relatively small province (yasuj) with almost all facilities needed for c llcll diagnosis and treatment. methods: finding the total number of cancer cases we reviewed records of all patients diagnoicd with cancer (icd - ) and registered in any hospital or pathology centre from until i n yasuj and all ( ) surrounding provinces. results: of patients who were originally residents of yasui province, . % wereaccoulll!d for yasuj province. the proportion varies according to the type of cancer, for exarnplecancetsofdiglstive system, skin and breast were more frequently reported by yasuj's health facilities whereas cancmoi blood, brain and bone were mostly reported by neighbouring provinces. the remaining cases ( . % were diagnosed, treated and recorded by neighbouring provinces as their incident cases. this is partly because of the fact that patients seek medical services from other provinces as they believed that the facil. ities are offered by more experienced and higher quality stuffs and their relative's or temporary acooiii' modation addresses were reported as their place of residence. conclusion: measuring the spatial incidence of cancer according to the location of report ortht current address affected the spatial statistics of cancer. to correct this problem recording the permanm! address of diagnosed cases is important. p - (c). providing primary healthcare to a disadvantaged population at a university-run commumty healthcare facility tracey rickards the. c:ommuni~y .h~alth ~linic (chc) is a university sponsored nurse-managed primary bealthwt (p~c:l clime. the clm c is an innovative model of healthcare delivery in canada that has integrated tht principles of phc ser · · h' . vices wit ma community development framework. it serves to provide access to phc services for members of th · · illi · dru is ii be . . e community, particularly the poor and those who use or gs, we mg a service-learning facil'ty f d · · · · · · d rionll h . . .,m.:. · t · . meet c ient nee s. chmc nursing and social work staff and srudents r·--· ipa em various phc activities and h .l.hont" less i . f . outreac services in the local shelters and on the streels to'"" popu auon o fredericton as well th chc · model iii fosterin an on oi : . • e promotes and supports a harm reduction . · local d!or an~ h ng ~art:ersh p with aids new brunswick and their needle exchange program, w tha ing condoms and :xu:t h:~~~e e~aint~nance therapy clients, and with the clie~ts themselves ~_r; benefits of receiving health f ucation, a place to shower, and a small clothing and food oai~· care rom a nurse p · · d d · --""~'i"· are evidenced in th r research that involved needsaans mvo ves clients, staff, and students. to date the chc has unacn- · sessment/enviro i . d ; •• '"""" ll eva uanon. the clinic has also e . d nmenta scan, cost-benefit analysis, an on-go...,, "".'i'~ facility and compassionate lea x~mme the model of care delivery' focusing on nursing roles wi~ cj rmng among students. finally, the clinic strives to share the resu•p v . -arch with the community in which it provides service by distributing a bi-monthly newsletter, and plllicipating in in-services and educational sessions in a variety of situations. the plan for the future is coolinued research and the use of evidence-based practice in order to guide the staff in choosing how much n~ primary healthcare services to marginalized populations will be provided. n- (c) tuming up the volume: marginalized women's health concerns tckla hendrickson and betty jane richmond bdrotbu:tion: the marginalization of urban women due to socio-economic status and other determinants negatively affects their health and that of their families. this undermines the overall vitaliry of urban communities. for example, regarding access to primary health care, women of lower economic surus and education levels are less likely to be screened for breast and cervical cancer. what is not as widely reported is how marginalized urban women in ontario understand and articulate their lack of access to health care, how they attribute this, and the solutions that they offer. this paper reports on the rnults of the ontario women's health network (owhn) focus group project highlighting urban women's concerns and suggestions regarding access to health care. it also raises larger issues about urban health, dual-purpose focus group design, community-based research and health planning processes. mdhods: focus group methodology was used to facilitate a total of discussions with urban and rural women across ontario from to . the women were invited to participate by local women's and health agencies and represented a range of ages, incomes, and access issues. discussions focussed on women's current health concerns, access to health care, and information needs. results were analyzed using grounded theory. the focus groups departed from traditional focus group research goals and had two purposes: ) data collection and dissemination (representation of women's voices), and ) fostering closer social ties between women, local agencies, and owhn. the paper provides a discussion and rationale for a dual approach. rax/ts: the results confirm current research on women's health access in women's own voices: urban women report difficulty finding responsive doctors, accessing helpful information such as visual aids in doctors' offices, and prohibitive prescription costs, in contrast with rural women's key concern of finding a family doctor. the research suggests that women's health focus groups can address access issues by helping women to network and initiate collective solutions. the study shows that marginalized urban women are articulate about their health conctrns and those of their families, often understanding them in larger socio-economic frameworks; howtver, women need greater access to primary care and women-friendly information in more languages and in places that they go for other purposes. it is crucial that urban health planning processes consult directly with women as key health care managers, and turn up the volume on marginalized women's voices. women: an evaluation of awareness, attitudes and beliefs introduction: nigeria has one of the highest rates of human immunodeficiency virus ihivi seroprrvalence in the world. as in most developing countries vertical transmission from mother to child account for most hiv infection in nigerian children. the purpose of this study was ro. determine the awareness, attitudes and beliefs of pregnant nigerian women towards voluntary counseling and testing ivct! for hiv. mnbod: a pre-tested questionnaire was used to survey a cross section '.>f. pregnant women ~t (lrlleral antenatal clinics in awka, nigeria. data was reviewed based on willingness to ~c~ept or re ect vct and the reasons for disapproval. knowledge of hiv infection, routes of hiv transm ssmn and ant rnroviral therapy iart) was evaluated. hsults: % of the women had good knowledge of hiv, i % had fair knowledge while . % had poor knowledge of hiv infection. % of the women were not aware of the association of hreast milk feeding and transmission of hiv to their babies. majority of the women % approved v~t while % disapproved vct, % of those who approved said it was because vct could ~educe risk of rransmission of hiv to their babies. all respondents, % who accepted vc.i ~ere willing to be tnted if results are kept confidential only % accepted to be tested if vc.t results w. be s~ared w .th pinner and relatives % attributed their refusal to the effect it may have on their marriage whale '-gave the social 'and cultural stigmatization associated with hiv infection for their r~fusal.s % wall accept vct if they will be tested at the same time with their partners. ~ of ~omen wall pref~r to breast feed even if they tested positive to hiv. women with a higher education diploma were times v more likely to accept vct. knowledge of art for hiv infected pregnant women as a means of pre. vention of maternal to child transmission [pmtct) was generally poor, % of respondents wm aware of art in pregnancy. conclusion: the acceptance of vct by pregnant women seems to depend on their understanding that vct has proven benefits for their unborn child. socio-cultur al factors such as stigmatizationof hiv positive individuals appears to be the maj_or impedi~ent towards widespread acceptanee of ycr in nigeria. involvemen t of male partners may mpro~e attitudes t~wa~ds vct:the developmentofm novative health education strategies is essential to provide women with mformanon as regards the benefits of vct and other means of pmtct. p - (c) ethnic health care advisors in information centers on health care and welfare in four districts of amsterdam arlette hesselink, karien stronks, and arnoud verhoeff introduction : in amsterdam, migrants report a "worse actual health and a lower use of health care services than the native dutch population. this difference might be partly caused by problems migrants have with the dutch language and health care and welfare system. to support migrants finding their way through this system, in four districts in amsterdam information centers on health care and welfare were developed in which ethnic health care advisors were employed. their main task is to provide infor· mation to individuals or groups in order to bridge the gap between migrants and health care providers. methods: the implementat ion of the centers is evaluated using a process evaluation in order to give inside in the factors hampering and promoting the implementat ion. information is gathered using reports, attending meetings of local steering groups, and by semi-structu red interviews with persons (in)directly involved in the implementat ion of the centers. in addition, all individual and groupcontaets of the health care advisors are registered extensively. results: since four information centers, employing ethnic health care advisors, are implemented. the ethnicity of the health care advisors corresponds to the main migrant groups in the different districts (e.g. moroccan, turkeys, surinamese and african). depending on the local steering groups, the focus of the activities of the health care advisors in the centers varies. in total, around individual and group educational sessions have been registered since the start. most participants were positive about the individual and group sessions. the number of clients and type of questions asked depend highly on the location of the centers (e.g. as part of a welfare centre or as part of a housing corporation). in all districts implementa tion was hampered by lack of ongoing commitment of parties involved (e.g. health care providers, migrant organization s) and lack of integration with existing health care and welfare facilities. discussion: the migrant health advisors seem to have an important role in providing information on health and welfare to migrant clients, and therefore contribute in bridging the gap between migrants and professionals in health care and welfare. however, the lack of integration of the centers with the existing health care and welfare facilities in the different districts hampers further implementation . therefore, in most districts the information centres will be closed down as independent facilicities in the near future, and efforts are made to better connect the position of migrant health advisor in existing facilities. the who report ranks the philippines as ninth among countries with a high tb prevalence. about a fourth of the country's population is infected, with majority of cases coming from the lower socioeconomic segments of the community. metro manila is not only the economic and political capital of the philippines but also the site of major universities and educational institutions. initial interviews with the school's clinicians have established the need to come up with treatment guidelines and protocols for students and personnel when tb is diagnosed. these cases are often identified during annual physical examinations as part of the school's requirements. in many instances, students and personnel diagnosed with tb are referred to private physicians where they are often lost to follow-up and may have failure of treatment due to un monitored self-administered therapy. this practice ignores the school clinic's great potential as a tb treatment partner. through its single practice network (spn) initiative, the philippine tuberculosis initiatives for the private sector (philippine tips), has established a model wherein school clinics serve as satellite treatment partners of larger clinics in the delivery of the directly observed treatment, short course (dots) protocol. this "treatment at the source" allows school-based patients to get their free government-suppl ied tb medicines from the clinic each day. it also cancels out the difficulty in accessing medicines through the old model where the patient has to go to the larger clinic outside his/her school to get treatment. the model also enables the clinic to monitor the treatment progress of the student and assumes more responsibility over their health. this experience illustrates how social justice in health could be achieved from means other than fund generation. the harnessing of existing health service providers in urban communities through standardized models of treatment delivery increases the probability of treatment success, not only for tb but for other conditions as well. p - (c) voices for vulnerable populations: communalities across cbpr using qualitative methods martha ann carey, aja lesh, jo-ellen asbury, and mickey smith introduction: providing an opportunity to include, in all stages of health studies, the perspectives and experiences of vulnerable and marginalized populations is increasingly being recognized as a necessary component in uncovering new solutions to issues in health care. qualitative methods, especially focus groups, have been used to understand the perspectives and needs of community members and clinical staff in the development of program theory, process evaluation and refinement of interventions, and for understanding and interpreting results. however, little guidance is available for the optimal use of such information. methods: this presentation will draw on diverse experiences with children and their families in an asthma program in california, a preschool latino population in southern california, a small city afterschool prevention program for children in ohio, hiv/aids military personnel across all branches of the service in the united states, and methadone clinic clients in the south bronx in new york city. focus groups were used to elicit information from community members who would not usually have input into problem definitions and solutions. using a fairly common approach, thematic analysis as adapted from grounded theory, was used to identify concerns in each study. next we looked across these studies, in a meta-synthesis approach, to examine communalities in what was learned and in how information was used in program development and refinement. results: while the purposes and populations were diverse, and the type of concerns and the reporting of results varied, the conceptual framework that guided the planning and implementation of each study was similar, which led to a similar data analysis approach. we will briefly present the results of each study, and in more depth we will describe the communalities and how they were generated. conclusions: while some useful guidance for planning future studies of community based research was gained by looking across these diverse studies, it would be useful to pursue a broader examination of the range of populations and purposes to more fully develop guidance. background: the majority of studies examining the relationship between residential environments and cardiovascular disease have used census derived measures of neighborhood ses. there is a need to identify specific features of neighborhoods relevant to cardiovascular disease risk. we aim to ) develop methods· data on neighborhood conditions were collected from a telephone survey of s, fesi· dents in balth:.ore, md; forsyth county, nc; and new york, ny. a sample of of the i.ni~~l l'elpondents was re-interviewed - weeks after the initial interview t~ measure the tes~-~etest rebab ~ ty of ~e neighborhood scales. information was collected across seven ~e ghborho~ cond ~ons (aesth~~ ~uah~, walking environment, availability of healthy foods, safety, violence, social cohesion, and acnvmes with neighbors). neighborhoods were defined as census tracts or homogen~us census tra~ clusters. ~sycho metric properties.of the neighborhood scales were accessed by ca~cu~~.ng chronba~h s alpha~ (mtemal consistency) and intraclass correlation coefficients (test-r~test reliabilmes) .. pear~n s .corre~anons were calculated to test for associations between indicators of neighborhood ses (tncludmg d mens ons of race/ ethnic composition, family structure, housing, area crowding, residential stability, education, employment, occupation, and income/wealth) and our seven neighborhood scales. . chronbach's alphas ranged from . (walking environment) to . (violence). intraclass correlations ranged from . (waling environment) to . (safety) and wer~ high~~~ . ~ for ~urout of the seven neighborhood dimensions. our neighborhood scales (excluding achv hes with neighbors) were consistently correlated with commonly used census derived indicators of neighborhood ses. the results suggest that neighborhood attributes can be reliably measured. further development of such scales will improve our understanding of neighborhood conditions and their importance to health. childhood to young adulthood in a national u.s. sample jen jen chang lntrodfldion: prior studies indicate higher risk of substance use in children of depressed mothers, but no prior studies have followed up the offspring from childhood into adulthood to obtain more precise estimates of risk. this study aimed to examine the association between early exposure to maternal depl'elsive symptoms (mds) and offspring substance use across time in childhood, adolescence, and young adulthood. methods: data were obtained from the national longitudinal survey of youth. the study sample includes , mother-child/young adult dyads interviewed biennially between and with children aged to years old at baseline. data were gathered using a computer-assisted personal interview method. mds were measured in using the center for epidemiologic studies depression scale. offspring substance use was assessed biennially between and . logistic and passion regression models with generalized estimation equation approach was used for parameter estimates to account for possible correlations among repeated measures in a longitudinal study. rnlllta: most mothers in the study sample were whites ( %), urban residents ( %), had a mean age of years with at least a high school degree ( %). the mean child age at baseline was years old. offspring cigarette and alcohol use increased monotonically across childhood, adolescence, and young adulthood. differential risk of substance use by gender was observed. early exposure to mds was associated with increased risk of cigarette (adjusted odds ratio (aor) = . , % confidence interval ( ): . , . ) and marijuana use (aor = . , % ci: . , . ), but not with alcohol use across childhood, adolescence, and young adulthood, controlling for a child's characteristics, socioeconomic status, ~ligiosity, maternal drug use, and father's involvement. among the covariates, higher levels of father's mvolvement condluion: results from this study confirm previous suggestions that maternal depressive symptoms are associated with adverse child development. findings from the present study on early life experi-e~ce have the potential to inform valuable prevention programs for problem substance use before disturbances become severe and therefore, typically, much more difficult to ameliorate effectively. the ~act (~r-city men~ health study predicting filv/aids, club and other drug transi-b~) study a multi-level study aimed at determining the association between features of the urban enyjronment mental health, drug use, and risky sexual behaviors. the study is randomly sampling foster sessions v neighborhood residents and assessing the relations between characteristics of ethnographically defined urban neighborhoods and the health outcomes of interest. a limitation of existing systematic methods for evaluating the physical and social environments of urban neighborhoods is that they are expensive and time-consuming, therefore limiting the number of times such assessments can be conducted. this is particularly problematic for multi-year studies, where neighborhoods may change as a result of seasonality, gentrification, municipal projects, immigration and the like. therefore, we developed a simpler neighborhood assessment scale that systematically assessed the physical and social environment of urban neighborhoods. the impact neighborhood evaluation scale was developed based on existing and validated instruments, including the new york city housing and vacancy survey which is performed by the u.s. census bureau, and the nyc mayor's office of operations scorecard cleanliness program, and modified through pilot testing and cognitive testing with neighborhood residents. aspects of the physical environment assessed in the scale included physical decay, vacancy and construction, municipal investment and green space. aspects of the social environment measured include social disorder, social trust, affluence and formal and informal street economy. the scale assesses features of the neighborhood environment that are determined by personal (e.g., presence of dog feces), community (e.g., presence of a community garden), and municipal (e.g., street cleanliness) factors. the scale is administered systematically block-by-block in a neighborhood. trained research staff start at the northeast corner of an intersection and walk around the blocks in a clockwise direction. staff complete the scale for each street of the block, only evaluating the right side of the street. thus for each block, three or more assessments are completed. we are in the process of assessing psychometric properties of the instrument, including inter-rater reliability and internal consistency, and determining the minimum number of blocks or street segments that need to be assessed in order to provide an accurate estimate of the neighborhood environment. these data will be presented at the conference. obj«tive: to describe and analyze the perceptions of longterm injection drug users (idus) about their initiation into injecting. toronto. purposive sampling was used to seek out an ethnoculturally diverse sample of idus of both genders and from all areas of the city, through recruitment from harm reduction services and from referral by other study participants. interviews asked about drug use history including first use and first injecting, as well as questions about health issues, service utilization and needs. thematic analysis was used to examine initiation of drug use and of injection. results: two conditions appeared necessary for initiation of injection. one was a developed conception of drugs and their (desirable) effects, as suggested by the work of becker for marijuana. thus virtually all panicipants had used drugs by other routes prior to injecting, and had developed expectations about effects they considered pleasureable or beneficial. the second condition was a group and social context in which such use arose. no participants perceived their initiation to injecting as involving peer pressure. rather they suggested that they sought out peers with a similar social situation and interest in using drugs. observing injection by others often served as a means to initiate injection. injection served symbolic purposes for some participants, enhancing their status in their group and marking a transition to a different social world. concl ion: better understanding of social and contextual factors motivating drug users who initiate injection can assist in prevention efforts. ma!onty of them had higher educational level ( %-highschool or higher).about . yo adffiltted to have history of alcohol & another . % had history of smoking. only . % people were on hrt & . % were receiving steroid. majority of them ( . ) did not have history of osteoporosis. . % have difficulty in ambulating. only . % had family history of osteoporosis. bmd measurements as me~sured by dual xray absorptiometry (dexa) were used for the analysis. bmd results were compare~ w ~ rbc folate & serum vitamin b levels. no statistical significance found between bmd & serum v taffiln b level but high levels of folate level is associated with normal bmd in bivariate and multivariate analysis. conclusion: in the studied elderly population, there was no relationship between bmd and vitamin b ; but there was a significant association between folate levels & bmd. introduction: adolescence is a critical period for identity formation. western studies have investigated the relationship of identity to adolescent well-being. special emphasis has been placed on the influence of ethnic identity on health, especially among forced migrants in different foreign countries. methodology: this study asses by the means of an open ended question identity categorization among youth in three economically disadvantaged urban communities in beirut, the capital of lebanon. these three communities have different histories of displacement and different socio-demographic makeup. however, they share a history of displacement due to war. results and conclusion: the results indicated that nationality was the major category of identification in all three communities followed by origin and religion. however, the percentages that self-identify by particular identity categories were significantly different among youth in the three communities, perhaps reflecting different context in which they have grown up. mechanical heart valve replacement amanda hu, chi-ming chow, diem dao, lee errett, and mary keith introduction: patients with mechanical heart valves must follow lifelong warfarin therapy. war· farin, however, is a difficult drug to take because it has a narrow therapeutic window with potential seri· ous side effects. successful anticoagulation therapy is dependent upon the patient's knowledge of this drug; however, little is known regarding the determinants of such knowledge. the purpose of this study was to determine the influence of socioeconomic status on patients' knowledge of warfarin therapy. methods: a telephone survey was conducted among patients to months following mechan· ical heart valve replacement. a previously validated -item questionnaire was used to measure the patient's knowledge of warfarin, its side effects, and vitamin k food sources. demographic information, socioeconomic status data, and medical education information were also collected. results: sixty-one percent of participants had scores indicative of insufficient knowledge of warfarin therapy (score :s; %). age was negatively related to warfarin knowledge scores (r= . , p = . ). in univariate analysis, patients with family incomes greater than $ , , who had greater. than a grade education and who were employed or self employed had significantly higher warfarm knowledge scores (p= . , p= . and p= . respectively). gender, ethnicity, and warfar~n therapy prior to surgery were not related to warfarin knowledge scores. furthermore, none of t~e. m-hospital tea~hing practices significantly influenced warfarin knowledge scores. however, panic ~ants who _rece v~d post discharge co~unity counseling had significantly higher knowledge scores tn comp~r son with those who did not (p= . ). multivariate regression analysis revealed that und~r~tandmg the ~oncept of ?ternational normalized ratio (inr), knowing the acronym, age and receiving ~ommum !' counseling after discharge were the strongest predictors of warfarin kn~wledge. s~ oeconom c status was not an important predictor of knowledge scores on the multivanate analysis. poster sessions v ~the majority of patients at our institution have insufficient knowledge of warfarin therapy.post-discharge counseling, not socioeconomic status, was found to be an important predictor of warfarin knowledge. since improved knowledge has been associated with improved compliance and control, our findings support the need to develop a comprehensive post-discharge education program or, at least, to ensure that patients have access to a community counselor to compliment the in-hospital educatiop program. brenda stade, tony barozzino, lorna bartholomew, and michael sgro lnttotl#ction: due to the paucity of prospective studies conducted and the inconsistency of results, the effects of prenatal cocaine exposure on functional abilities during childhood remain unclear. unlike the diagnosis of fetal alcohol spectrum disorder, a presentation of prenatal cocaine exposure and developmental and cognitive disabilities does not meet the criteria for specialized services. implications for public policy and services are substantial. objective: to describe the characteristics of children exposed to cocaine during gestation who present to an inner city specialty clinic. mnbods: prospective cohort research design. sample and setting: children ages to years old, referred to an inner city prenatal substance exposure clinic since november, . data collection: data on consecutive children seen in the clinic were collected over an month period. instrument: a thirteen ( ) page intake and diagnostic form, and a detailed physical examination were used to collect data on prenatal substance history, school history, behavioral problems, neuro-psychological profile, growth and physical health of each of the participants. data analysis: content analysis of the data obtained was conducted. results: twenty children aged to years (mean= . years) participated in the study. all participants had a significant history of cocaine exposure and none had maternal history or laboratory (urine, meconium or hair) exposure to alcohol or other substances. none met the criteria of fetal alcohol spectrum disorder. all were greater than the tenth percentile on height, weight, and head circumference, and were physically healthy. twelve of the children had iqs at the th percentile or less. for all of the children, keeping up with age appropriate peers was an ongoing challenge because of problems in attention, motivation, motor control, sensory integration and expressive language. seventy-four percent of participants had significant behavioral and/or psychological problems including aggressiveness, hyperactivity, lying, poor peer relationships, extreme anxiety, phobias, and poor self-esteem. conclusion: pilot study results demonstrated that children prenatally exposed to cocaine have significant learning, behavioural, and social problems. further research focusing on the characteristics of children prenatally exposed to cocaine has the potential for changing policy and improving services for this population. methods: trained interviewers conducted anonymous quantitative surveys with a random sample (n= ) of female detainees upon providing informed consent. the survey focused on: sociodemographic background; health status; housing and neighborhood stability and social resource availability upon release. results: participants were % african-american, % white, % mixed race and % native american. participants' median age was , the reported median income was <s , year, and % reported receiving a high school diploma or equivalent. women reported a number of health conditions rypical of underserved populations, including asthma ( %), sexually transmitted infections ( %), high blood pressure ( %), hcv ( %), diabetes ( %) and hiv ( %). nearly half ( %) did not anticipate having a place to stay for at least days upon release. factors significantly associated housing stability upon release were: high family support score (adjusted odds ratio [aor) . ; % confidence interval ( % cl) . , . ), high neighborhood stability score (aor . ; % cl . , . ), wanting a commercial sex worker (csw) support group (aor . ; % cl . , . ); and identifying as bisexual (aor . ; % cl . , . ). women desired employment ( %), housing ( %), education ( %), drug treattnent ( %), help with custody of children ( %), childcare ( %), and domestic violence suppon ( %) services. conclusions: female detainees represent one of urban centers' most marginalized pcjpwatioos. short periods of detention represent a unique opportunity for _interven?~ns bri~ co~s and public health institutions. service providers should collaborate ~ th local ~ails to .p~de a con uwnof care for female detainees upon release that includes transportation , housing, residential drug treallllcnt, employment, education, family reunification, childcare and domestic viol~nce su~rt. ~pecial attenlion is warranted to lesbian and bisexual women and csws, who may be especially margmalized &om family and service-based support networks. introduction: "health care and ethnic minority immigrants" examines how health care policy dil· ferences between canada and the united states impact the health-related hardships, access and use of preventative care, and health outcomes of urban ethnic minority immigrants in both countries. methods: the findings of this paper build on the results of my qualitative comparative study of hotel workers in vancouver, bc and seattle, wa that revealed greater health related hardships for similarly matched employees in seattle compared to vancouver. in this paper, i examine the generalizability of these findings at the cross-national level for similar ethnic minority immigrant groups. i compare the impact of health care policy differences on specific groups that have emigrated to cities in both canada and the united states. these include immigrants from china, viemam, philippines, west indies, africa, sri lanka, pakistan, and latin america. comparative statistical analysis -utilizing rel· evant data from statistics canada and the u.s. census -reveal the extent to which health policy differ· ences help explain how current health policy in the united states disadvantages urban ethnic minority immigrants. results: many ethnic minority immigrants are a part of the working poor, a group which disproportionately lacks health insurance coverage in the united states. their position in the labour market makes them most vulnerable to exclusion from health care services. the data reveals how current u.s. health policy creates barriers for recently arrived ethnic minority immigrants to access health insurance and care. it remains difficult to ascribe health outcome differences directly to policy differences because of the challenge in disentangling the complex interacting interventing variables, including income inequality, that determine health outcomes. yer suggestive evidence suggests that health policy in the united states is harming the health of urban ethnic minority immigrants. the current health policy regime in the united states harms the health access, care, and outcomes of urban ethnic minority immigrants. comparing the fortunes of similar immigrants in cana· dian and u.s. cities reveals these patterns of disadvantage and some of their consequences. these barriers are an understudied factor in the sociological literature on "segmented assimilation" and social exclu· sion. the paper ends with policy recommendatio ns to improve access to health care among ethnic minor· ity immigrants in both countries, with the goal of reducing health related hardships, and improving health outcomes. mass index deyu pan, richard baker, and keith norris badtgrou~ over the past decades, there has been dramatic increase in prevalence of obesity in the us population. however, the relationship between obesity and the prevalence of cardiovascular dis· ease (cv~) risk factors in different race/ethnic groups over time is not well known. . ik~rgn: _we use cross-sectional , nationally representative surveys: national health and nutri· t nal examination survey (nhanes iii - (n= ) and nhanes nhanes - , including white, black, and hispa~ic races who were no~preg~ant, aged to years. res lt : the preval~nce of high cholesterol level (~ mg/dl), untreated high blood pressure ( : l / mm hg) an~ diabetes were calculated according to bmi group (lean, < ; overweight, - ; and obese, : ) for different race/ethnicity groups. over the approximately years period (from l ~ ~o [ ] [ ] [ ] [ ] , reducrion in cvd risk factors in non-hispanic white has been observed. for mmonty race/~hnicity groups, black and hispanic, there had been increases in prevalence in high blood fa pressure and diabetes. the lean group experienced larger increase in prevalence of those cvd risk ctors. . fo~~ the prevalence in cvd risk factors over time had reduced in most of the bmi ca egoes r t e w ~~e population. however, for black and hispanic, prevalence of of cvd risk factors ave generauy uncreased, especially in overweight and obese groups. methods: strategies identified to achieve these goals include: developing meaningful neighbourhood and district boundaries for comparing health information, providing free access to neighbourhood health profiles (including relevant data at the smallest level for which valid rates could be calculated); mapping relationships of inequality at a variety of nested levels; providing a range of formats (maps, tables) to meet the needs of users; providing technical support; seeking user input to advance and improve the site; and conducting workshops to foster access and use of data for decision-making , advocacy and collaboration. an evaluation strategy is being developed to assess the efforts and impact of these strategies. a preliminary assessment of the results of the first six months of activity will be completed in october . results: significant differences in health are shown at all the geographic levels indicating success in developing the boundaries. results tabulated for the first six months use of the site include: site visits; media use; reference/acknow ledgement of the site in other documents; number of contacts through presentations and workshops; feedback from users identifying strengths and limitations; and, response from health decision makers. members of the partnership are identifying additional tools and services to further support actions that reduce health inequalities. the assessment will be used to develop more specific goals, targets and monitoring mechanisms. conclusions: our experience with paper-based health profiles indicates that they have been used extensively for program planning and advocacy. the greater availability of information in a publiclyavailable web-based format is expected to translate into even greater usefulness and wider application. the web site has had considerable usage to date, extensive media coverage. site users and workshop participants have provided positive feedback and suggestions for next steps. the six month review will be available in october . in india, more than and a half people are hiv-positive and half a million have aids. india currently has the largest number of positive people in the world, oumumbering south africa and accounting for nearly one tenth of the global hiv/aids prevalence. the world bank predicts that by , there will be million hiv/aids cases in india. the central challenge facing hiv prevention efforts in south asia today is learning how to respond to the societal determinants of vulnerability to hiv. hiv/aids is an issue largely engulfed by social stigma. stigma and discrimination are often considered the foremost barriers to effective poster sess ns v prevention and care initiatives. stigma can make a person afraid of disclosing their status~ ~yone el se, and may make them feel depressed or alone. stigma can .also le~d to poor adherence to medicanon, ~ likelihood to access health and social services, and less desire to hve. hiv+ men and women may beafraidtotd! their co-workers that they have hiv for fear of their reactions or for fear of losing their jobs. in a study conducted of people living with hiv/aids in delhi, india ov~r. -~, many respo~ts shared their experiences of discrimination in their families, in their communmes, an~ m health ~e settmgs. these findings will be shared in the workshop, and will be compa~ed to m~ ex~nences workmg as an ~ co~l~ at the center for aids prevention studies in san francisco, cahforma and congreso de lannos unidos m philadelphia, pennsylvania. the workshop will include an overview of hiv/aids in urban contexts in tht united states (los angeles, san francisco, new york, philadelphia) and south asia (delhi, hyderabad, chennai). differences in methods for outreach, prevention and treatment efforts between devdoped world and developing world contexts will be discussed. a large portion of the workshop will be centered on discussion. participants will engage in an exercise to categorize their ideas of stigma. the workshop will also include a powerpoint presentation on the quantitative data gathered from the survey. the number of homeless and runaway youth is increasing in toronto, which is currently home to out of youth in the gt a who live alone, and it is the preferred locale for the street-involved and homeless youth. the city's youth population is expected to grow by nearly % by , the school dropout rate is rising, and there are is a paucity of empirical data on what works with these at-risk youth. over a two-year period, ( ) ( ) ( ) , youthlink-inner city, conducted an evaluation of the impact of a harm reduction program aimed at reducing street youth's risk of contracting/infecting others with the hep c virus, which has both short-term and long-term deleterious effects. demographic data from street-youth, along with resources/services used, employment methods, type and frequency of drug use, health status, police contacts, and their views of program impact were analyzed using a standardized sur· vey. additionally, focus groups with youth, agency staff and community key informants were conducted, as well as in-depth interviews with three youth, over a sixth-month period. this paper details study results, which both inform both practice and future study about what works, why it works, and how best to work with these vulnerable youth. sho~ed .that the wasteland in this area was contaminated by as cd zn pb cu simultaneously. the con-ta~matton of as ~d was quit significant. the contamination problems and environmental issues in this region are very. serious. the awareness on environmental and health issues was investigated by spot survey and analysis. overall awareness among the residents in the region is very poor. the measures must be taken to assu~e t~e .sustainable economy development by local and central gorvernments. keywords nandan guangx ; mmmg area; environmental awareness. concern like, epileptic fits, vision problems, earache, cough of more than weeks and urinary problems. ninety-five subjects did not take bath regularly and were exposed to sex. the health problems identified are only of a particular point of time and it may be difficult to interpret the depth of "iceberg" of the street children's world also draw the health-illness continuum. periodic interaction and follow-up is very difficult as they generally disappear from the research setting due to their frequent mobility for survival measures. as per the prediction of the iceberg theory, only some problems may have been identified, larger problems in respect to their health may not have been identified. in spite of various limitations, this attempt had proven that, it is possible to enter the street children world, explore the iceberg of illnesses, and establish data of health-illness continuum through an effective nursing agency. it is recommended to deworm these children, provide nutritional education, establish "condom corners" and "street children help line" in the city and urban slum areas and undertake action research on their health. malnutrition is a serious problem in developing countries like bangladesh. malnutrition causes a great deal of child suffering. malnutrition is one of the major causes of morbidity and mortality among the child. the aim of present study was to investigate the nutritional status and its relation to socioeconomic conditions of urban disadvantaged child of under five years age. nutritional status was determined by anthropoemetric measurement(heig ht, weight, mid-arm circumference etc.). determination of total protein and serum albumin were done for biochemical examination. haematological examination was done by blood haemoglobin profile estimation by cynmethhaemoglob in method and determination of haematocrit value or packed cell volume (pcv). stool examination for ova of hook worm, round worm, trichuris species and other species were also done. relevant information on socioeconomic characteristics was recorded by interviewing the house hold head using pretested questionnaire. our study demonstrated that nutritional status of the children are positively correlated with family income, parents level of formal education and negatively related to the family size. the effect of family income on the nutritional status, haematological and biochemical indices of urban disadvantaged child under five will be discussed in detail which will help us to determine proper way of utilization of health care facilities exists in developing countries. introduction: with the increase in morbidity and reduction in mortality and with the introduction of highly active antiretroviral therapy (haart), there is increasing focus on the determinants of healthrelated quality of life (hrqol) in hiv-infection. the focus on the present study is to examine the relationship between social support, depression, and hiv disease severity, and the extent to which these variables impact on hrqol in adult men with hiv-infection. methods: as part of a larger ongoing natural history study focusing on the neurobehavioural complications of hiv and aids, we administered questionnaires to assess depression (beck depression inventory), social support, and hrqol (mos-hiv) to adult men with hiv-infection. a structured interview was used to collect health information and data on hiv disease severity. physical and mental health summary scores (phs and mhs) were derived through principal components analysis. participants were grouped according to level of social support: "well supported" (n= ), "moderately supported" (n= ), "little or ineffective support" (n= ). analysis of variance was conducted to assess the effects of three levels of perceived social support, depression status (present vs absent), and hiv disease severity (aids vs non-aids) on mental and physical health dimensions of hrqol. potential interaction effects were also evaluated. results: social support was found to have a significant effect on both mhs and phs. presence of depression was found to have a significant effect on mhs but not phs. hiv disease severity (presence of aids diagnosis) was found to have a significant effect on phs but not mhs. manov a analyses revealed no significant interactions effects. conclusions and implications: level of social support, presence of depression and hiv disease severity were shown to have independent effects on hrqol. feeling "well supported" appears to have significant benefits for mental and physical health. biological indicators of hiv disease appear to have a selective impact on physical health while presence of depression is related to significant reductions in mental health. the development and evaluation of behavioural interventions to improve perceived social support network and depression will likely result in significant improvements in health outcomes of adults with hiv and aids. introduction: ongoing medical advances have greatly enhanced the longevity of penons living with aids (plwa). however, for certain subgroups living with hiv/aids, including, members of minority groups, women and the economically underprivilege d, aids outcomes have not changed so favorably. one obvious factor to consider when explaining disparities in aids outcomes is the environ· ment within which an individual resides. few studies of aids outcomes have focused on how commu· nity setting influences the effectiveness of care delivery. the principle research questions were: ) what is the relationship between the locations of areas with concentrations of pl wa and the distribution of both primary and ancillary service providers? ) how has the widespread availability of haart (after ) impacted aids outcomes at the community level? ) how do aids mortality and fatality rates vary when related community characteristics, such as household income, ethnic mix, and geographic access to primary and ancillary hiv/aids services are considered? we examine this issue across residential communities in the los angeles area. methods: los angeles county's comprehensive aids service providers database (compiled and maintained by aids project los angeles) was geo-referenced and distances between weighted mean population centers and the nearest hiv/aids service providers were calculated to provide a measure of access which was then merged with aids diagnosis and mortality data along with relevant socioeconomic and population indicators and for analysis using bivariate and multivariate statistics at the zip code level. results: there is a growing disparity in hiv/aids outcomes between low-income minority areas and affluent non-minority areas in the post-haart era (p = . ). ancillary aids services such as case management and counseling and testing are located near the places where low income hiv/aids service consumers are likely to live (p =. ). in spite of having more access to ancillary services low income areas continue to be associated with smaller decreases post-haart aids mortality rates (p= . ). conclusions: given the increasing disparities in aids outcomes between lower and upper income communities in the post -haart era, more specific research into the capacities of aids services providers and the efficiency of their interventions is required. although it is clear that ancillary services are operating in the areas of greatest need, their effectiveness remains limited. understanding the reasons for t~is, be they lack of adequate resources for inner city service providers, failure to reach target popula· tmns or other causes, requires additional research. in ? , y.out~ who were able to speak either french or english and had been absent from their parent's/ c~regivers ~es. dence for at least three consecutive nights took part in the survey which consisted of inter· viewer-adm ms tered question~aires. p.arti~i~an~s were recruited from drop in centres in cities across <?-nada.y~uth self-report as either using in ect on or non-injection drugs. statistical analyses were car· r ed out using sas version . the 'home' is a contested site for many women living in urban areas. women living in poverty and using illicit drugs are largely excluded from participation in dominant 'home-base' gender roles of wife and mother because of economic disadvantage. they thus 'make home' in ways that are specific to their everyday experiences. while research has established links between housing, health and drug use, this literature does not tend to consider the meanings that home may have within the lives of women who lack access to adequate tenured living spaces. this presentation reports the findings of my master's thesis work. using grounded theory methodology within a poststructuralist feminist conceptual framework, i conducted in-depth, open-ended interviews with women living in the toronto area. the women were recruited from within the community through posters at different social service agencies (e.g., drop-in centres, community health centres). they were asked to describe their housing experiences and what home meant to them over the course of their lives. through the data analysis process, a substantive theory of 'making home' for women living in poverty and using illicit drugs emerged. the central concept of making home is a continual process of learning about and interacting with the environment. the process of making home entails different subprocesses: finding home (knowing what is available and accessible, and accessing home), adaptation, and leaving home. the different meanings of home that women developed from their experiences and knowledge emerged as critical components for the process of making home. the women i interviewed were very mobile and experienced constant change with regards to home. home was not considered only in relation to physical living space. home could be made within a relationship or with regards to a possession. while dominant meanings of home relation to tenured living spaces are generally positive, my research indicated that home could also be a negative context. the presentation will describe my research process and findings as well as the theoretical and policy implications of my results. in the western democracies, social citizenship bundles the right to social provision (defined as a share of the social good, not necessarily proportionate to the market value of a citizen's contribution) with participation in the paid labour force. for this reason, social citizenship rights, which usually involve some kind of redistributive measures, are a key mechanism by which states ensure economic equality, or at least, economic equality of opportunity, but are also a mechanism of social exclusion. social rights are inscribed around a single kind of relationship, that which exists between a male family breadwinner and the paid labor market; those who make economic contributions that fall outside this relationship -such as unpaid care-work, or, work that occurs in shadow or underground economiesare to a greater or lesser degree barred from accessing citizen-based social provisions. furthermore, social provision that occurs outside of the breadwinner/market-eco nomy dyad is very often meanstested and is accompanied by regulatory state apparatuses (this includes a range of social services, from welfare payments, to child-care subsidies, to disability pensions). social citizenship is thus stratified; the legal relationship that is at the heart of social citizenship acts as a form of social closure against claims for a share of the social good made by those who are 'lesser' citizens than others. of particular interest in this paper is how citizenship inequalities translate into inequalities in the social provisions that emerge from economic participation: the right to safety on the job, protection from employer harassment, protection from the vagaries of the market as well the right to adequate, comprehensive, and appropriate health services. drawing on mixed methods, longitudinal data from adult sex workers (n= ) located in two research sites with different social welfare regimes -one in canada and one in the u.s. -we examine the consequences of working in a "shadow" or "underground" economy on various facets of health and access to health services, taking into consideration the mediating role that citizenship constructs and social welfare regimes play in accessing other key social and economic determinants of health. methods: the study population included methadone patients (re)admitted at the mhs in the period from / / to / / , born in the netherlands, morocco, surinam, dutch antilles or turkye, and officially registered in the population register of amsterdam. the population register was used to ascer· rain the vital status. causes of death were provided by the central bureau of statistics. mortality was categorised as hiv related, directly drug related (overdose) and other.mortality. results: the methadone patients had the following characteristics: years of age at entry; % male; % ethnic minority; % ever injected. in total, personyear (py) of observation time and deaths ( % hiv related, % overdose; % other) were observed. hence, the crude mortality rate was / py ( % ci - / py). the percentage of (ever) injectors was higher among the native dutch than among the ethnic minorities, % and % respectively. higher rates were observed among native dutch drug users compared to those belonging to an ethnic minority (age adjusted hazard ratio (hr) . ( % ci . - . ). the age adjusted hr of (ever) injecting drug users versus non injecting users was . ( % cl . - . ). after additional adjustment for route of administration a non significant difference between the dutch and ethnic minorities remained (hr . , % cl . - . , p-value . . conclusion: the mortality rate among the heroin users in amsterdam is strongly affected by the high prevalence of non-injecting drug use. moreover, this study confirms that differences in mortality between the native dutch and the ethnic minorities is related to differences in route of administration. the ongoing reduction of injecting drug use (due tot selctieve mortality, and switching route ofadministration and popularity of crack cocaine) may lead to a further reduction of mortality rates among heroin users in amsterdam. interventions preventing the initiation of injecting should be encouraged. . introduction: food insecurity is an inequality that is central in the lives of many low-income cana· d ans. people lack food security when regular access to nutritious food is limited or variable due to high prices'. low income, lack of transportation or inadequate food distribution, or they become disadvan· taged m other w~ys through the acquisition of food. a group comprising academics, health profession· als, and commumty workers who have experience in food insecurity, developed a pilot study in ottawa that sought to und~rstand the lived experience of food insecurity. the study also used the united states department of agriculture (usda) community food security module. methods: a series of group meetings determined the best research approaches; questionnaires and consent forms were developed by a working group. twenty-three self-identified food insecure respon· dents were interviewed. the data were analysed using frequency distributions· the food security module was coded according to the usda coding guide, and open-ended responses w~re coded using a grounded approach. renlts: preliminary results from our pilot study have given the research team cause for considerable concern. out of households without children, experienced food insecurity with hunger; ~ere at the severe l~vel. out of households with children, experienced food insecurity with hunger. ~•rst person reflecnons commonly featured feelings of depression low self-esteem and despair. participants' account tha d . an cu ty gettmg to the store, severely limited putting knowledge and skills mto practice. l'oster sessions v conclusion: based on these early findings, our research team is looking to challenge what appear to be assumptions about poverty and food insecurity and for best ways to use this information. some policy approaches and interventions that encourage people to eat better and exercise more, may be missing the mark for low-income individuals, and may serve to maintain food insecurity. future research will build on this pilot. with methods augmentation, and a comprehensive knowledge dissemination plan, we hope co contribute to research and policy frameworks at all levels. ps- (a) mental health and the corrections system: population-based analyses in urban, semi-urban, and rural settings julian somers, robert watts, and michelle patterson introduction: according to recent epidemiological research, rates of mental disorders vary considerably across countries and across regions within countries. nevertheless, rates of mental disorders (including substance use disorders) are consistently higher in populations involved in the corrections sys- em. courts have long recognized the heavy burden of mental illness within their purview, and have developed innovative programs to better manage the needs of such individuals. the majority of these innovations (e.g., specialized courts) exist in urban settings. however, few studies have examined the degree of variability in rates of different mental disorders between courts in urban and other settings (e.g., semi-urban, rural). variability between courts in different settings, if present, holds implications for needs-based resource planning. the present study was conducted as part of a long-term inter-ministerial collaboration in british columbia (bc). analyses were conducted on linked administrative data regarding population health and correctional services. a database was constructed including all individuals sentenced in bc in a single year (n= , ). corrections records were matched to records of health services utilization (hospital and outpatient services) for mental disorders and substance use disorders in the years preceding sentencing. services for mental health and substance-related problems were aggregated into three groups: severe mental illness (smi); less-severe mental illness (lsmi); alcohol/other drug (ad). courts were grouped, based on their annual volumes, inro three categories: "urban"; "semi-urban" and "rural." rates of service use for mental disorders were compared between groups for -year and -years preceding sentencing. results: there were significant differences in the rates of mental disorders in courts of different size (urban, semi-urban, rural) . however, differences between the rates of disorders within each of these groups exceeded the discrepancies between groups. comparatively high and low rates of disorders were observed in courts of each size. moreover, the courts with the highest rates of certain disorders (e.g., ad) did not have the highest rates of other types of mental disorders (e.g., smi). conclusions: rates of mental disorders differed significantly among the annual populations sentenced across courts in bc. urban courts (which process comparatively large numbers of people) have implemented services to address the needs of the mentally ill. the present analyses strongly suggest that program development should be closely linked to the demonstration of need. the results caution that a uniform approach to court programs for the mentally ill is likely to be inefficient, over-supplying services in some settings and underestimating need in others. results: public settings used for injection are characterized by highly unhygienic conditions, the presence of unsafely disposed syringes, limited availability of sterile syringes and a lack of sterile water for injecting. a number of unsafe injection practices observed were common among public injectors. the presence of police officers nearby and the potential of assault by street predators fostered rushed injecting among those consuming drugs in public spaces. the ecological features of these environments encourage unhygienic and unsafe injecting practices, heighten risk for overdose and the transmission of blood borne viruses. introduction: approximately % of women experience depression in the first weeks or months after giving birth. although it has been argued that postpartum depression (ppd) is a culture-bound p~ nomenon, experienced only in western, industrialized countries, recent international research studies have confirmed that the prevalence of ppd is similar around the world. however, little is known about variables that may influence the experience of ppd in women from diverse cultures and immigrant women. research is needed to identify the role culture may play in the presentation of ppd (i.e., types of symptoms most commonly reported), how women from various racial, ethnic and cultural backgrounds perceive and attribute their symptoms of ppd, and finally, how culture can be appropriately addressed in ppd treatment programs. method: to examine the role of culture in ppd, semi-structured interviews and self-report question· naires were administered to clients of the women's health centre of st. joseph's health centre, tor· onto. participants were identified as either first generation canadians (relative newcomen) (n= ) or second generation canadian (parents were immigrants to canada) (n= ). data were collected qd these two groups of women based on: severity of depression, symptom presentation, perceived role of social supports and culturally-specific traditions, and barriers and responses to treatment. the interview data were analyzed using qualitative methods (thematic content analysis), and the following themes were identified: ) stress about passing on their culture to their children, ) lack of social support and feelings of isolation, ) perceived importance or lack of importance of cultural based tra· ditions, ) conflicts with family members. about cultural traditions and beliefs, ) mental health stigma within ethnic communities and beyond, ) race-and sex-based discrimination, and ) language barriers. conclrllion: identifying the role culture plays in the presentation of ppd, and how women from diverse backgrounds perceive and attribute their symptoms of ppd, is critical in order to establishcultur· ally appropriate guidelines for treatment options. furthermore, information gathered from this study can be used to develop policies and resources for delivering culturally competent care for newcomer wo~ who are dealing with ppd as well as the issues around acculturation (i.e., language barriers, racism). llus is of particular importance for urban health centers which provide postpartum care to diverse groups of women, and particularly recent immigrants or newcomers. ps-~ (al. contaminated 'therapeutic landscape': perceptions of the aamjiwnaang fint nation keyln smith and isaac luginaah . in~: this. paper pres;ents the findings of an ongoing study among the aamjiwnaang f!rst nanon. aam wnaang is located m the heart of samia's 'chemical valley', surrounded by cherrucal ~(ants such as esso, imperial oil, shell, suncor energy, and canada's largest hazardous waste disposal sate. safety kleen. this fint nation community is located within the st. clair river •area of concem'. as destgna~ by health canada for the population of samia and the surrounding region. although this comm_umty, by way of. its proximity to the numerous chemical plants is already exposed to high levels pollu~on, recent che?ucal dumping in ~mjiwnaang, as well as a failed proposal for another ethanol plant m the community, only helped to mtensify community concerns about potential health impacts of exposure. research on the cultural beliefs and traditions of first nation communities has established that th~ ~isting rel~tionship between first nations people and 'mother earth' is not only physical, but also_ spmtual. in this study we explore how the complex relationship between the aamjiwnaang first naaon and 'mother earth' be ha · · · i .. may c ngmg a contammated 'therapeutic' landscape. the study a so ~lores h?w aam wnaang residents are coping with these changes and with the probable conramina· boa of their community. ra!jts: aamjiwnaang residents acknowledge that they are living in a contaminated environment and are being impacted by emissions from the surrounding 'chemical valley' especially for future generations, and have expressed concerns that members of the community and mother earth are 'sick' as a result of this exposure. while moving from that 'place' has been discussed, residents have strong personal and generational connections to the land and insist however, that aamjiwnaang is their 'home' and will remain that way despite growing community concerns about the impact from industry. the contribution of this study lies in the direct involvement of community leadership in designing and conducting this research and distributing the results to further local policy development regarding community concerns on the reserve. background: truck driver are at very high risk for drug abuse because the factor contributing to drug abuse among driver are multiple. it is important to gain an understanding of the key factors that contributing to drug abuse among truck drivers. methods: seventy-truck driver aged - years were conveniently selected from the population. all the participants were male. an interview schedule was developed in the light of literature data and data were collected by personal interview with informed consent in selected urban area of eastern part of nepal. results: a considerable percentage of truck driver have less knowledge about drug abuse, its effect on body and their complication. majority of the participants ( %) explained that lack of education, financial crisis were leading factors of drug abuse. the average numbers of respondents were believed that lack of meaning in life, marital disharmony. friendship with drug abuser, stress, tiredness, modernization of life pattern and freedom from the home pressure were the influencing risk factors to drug abuse. conchuion: this study reveals those truck drivers are at risk in urban area for developing drugs abuse, mostly influenced by social and environmental factors. hence, these groups should undergo certain educational programme to prevent not only drug abuse, but also prevent transmission of infectious disease among these groups. introduction: food insecurity is an inequality that is central in the lives of many low-income canadians. our group of university researchers, health professionals, and community developers conducted a study in ottawa with community workers who work with people identified as food insecure. the purpose of the study was to understand the nature of their work, and their perspectives, perceptions and experiences of the causes and consequences of food insecurity. (a parallel study was conducted with food insecure participants). methods: sampling was through local knowledge of organizations involved in the provision of food to community members. written permission for the researchers to contact workers in confidence was obtained from each organization. thirteen in-depth interviews were conducted. the interviews consisted of a number of open-ended questions. the data were collated, and analysed using a grounded approach. results: workers interviewed represented organizations that offered diverse programming and methods of food distribution intended to address the needs of the community. the provision of food was seen as a necessary response to address hunger that arose for the majority from poverty caused by low income, or levels of government income support and safety nets that were insufficient to support food requirements. workers reported that food requirements varied according to different. ethnic backgrounds, ages of recipients and family configurations, and with food preferences, and d'.etary (health) requirements. workers' observations of the effects of insufficient food on adults and children such as depression, low energy and non-participation or social disengagement matched those of food insecure respondents. food insecurity was cited as "another srressor among the mountain of problems." overall, workers presented a picture of a silent, stigmatized, poor population including children, and a lack of advocacy to address the issues. be tha th · ·ty the results suggest that workers and organizations, like the commuruty mem rs t ey msecun • · · · · f ilab'l' f food · t d ·n thei·r ab 'l 'ty to address food insecurity. l m tanons m terms o ava ty o , serve, are restnc e . . funding, and donations appeared to set the para? eters of pr~g:am r.espon~ to commuruty food msecurity. workers were concerned with program des g": and a~m mstranon that m general addr~d hunger on an emergency short-term basis, although food msecunty was long-ter_m for ~any. sustainable solutions that include knowledge translation strategies, and health and social pohcy responses were suggested and will be explored in future research that hopes to build on this pilot. background: socioeconomic deprivation as well as low levels of soc!al s.uppoi:r have .been associated with poor outcomes following cardiac surgery. pre-operative depression m ~anents with coron~ry artery disease awaiting cabg ranges from - % and is an independent predictor of post-operanve mortality. since st. michael's hospital has a large inner city population, this study was designed to determine the both the prevalence of depressive symptomatology (ds) in patients awaiting cabg as well as its relationship with socioeconomic status (ses) and social support. methods: consecutive patients referred for isolated cabg were invited to complete the centre for epidemiological studies depression scale (ces-d) as well as a social support scale and a life stressors inventory. a ces-d score of : represents mild ds and a score of : represents moderate to severe ds. participants also recorded information on functional status, perceived progression of heart failure, demographic and ses variables. all participants with ces-d scores : were considered to have ds. results: of the patients ( %) who returned the survey, ( . %) of participants had a ces-d score : with ( . %) of those having scores suggestive of severe depression. females and those with ongoing medical concerns tended to have more ds (p= . and p= . respectively). age was not related to ds. perceived worsening of symptoms and increased ccs angina class were significantly related to the presence of ds (p= . and p= . respectively) but not the number of diseased heart vessels. satisfaction with personal relationships including having someone to confide in (p= . ), feeling lonely (p= . ) and not having a partner (p= . ) were significantly related to ds. being very upset by a recent breakup in the immediate family was also significantly related to ds (p= . ). having greater than a grade education was the only ses variable related to ds (p= . ). multivariate logistic regression suggested that not being partnered and having low education were the most significant predictors of ds. conclnsion: pre-operative depression is present in at least one quarter of patients referred for cabg. since ds is related to poor outcomes following cabg, single patients with few social supports and low education should be considered at high risk for ds. these findings support the need for the development of supportive interventions in patients at risk in order to decrease post-operative morbidity. this study examines the relationship between childhood sexual abuse, sexual assault during adolescence, and hiv-risk-related behaviours in a sample of homeless youths. over the past decade, there has been increasing research devoted to the impact of childhood sexual abuse. some studies have suggested that the experience of childhood sexual abuse is associated with substance use and abuse, at· risk sexual behaviour and subsequent higher rates of hiv infection (ompad et al., ; cinq-mars et al., ; brown et al., ) . other studies have found that childhood abuse, especially sexual abuse, is c_o~n among stree~ youth (noell et al. ). this study compares sexually abused males and females livtng on the street ~th non-sexually abused street youth, with regards to unsafe sexual behaviours and e~ures to potmnal t:dv sources (e.g., tattooing, body piercing and injection drug use). the hypothe-sis oft~ ~nt study is that the prevalence of hn-risk-related behaviours will be higher among street youth vtctuns of sexual abuse than those who have not been sexually abused. the sample includes youths aged to who met specific criteria's for itinerancy ( male and female, with a mean ~of . y· and a standard deviation of . ). they were recruited through five organisations working ~th~ you~ and were~ of an ongoing cohort study. all youth completed a to minute ques· ~onnaue on their sexual behaviours, use of drugs and alcohol and other hiv risk behaviours. oral spec· unens for hiv testing were. also collected. a total of ( . %) youth reported at least one incident of ~i •~use/assault ( ~ girls ( . % of all the girls) and boys ( . % of all the boys]). preliminary descnpnve analyses pomt to sexually abused/assaulted youth showing the highest prevalence of sexual poster sessions v at-risk behaviours. for example, . % of sexual abuse/assault victims have engaged in prostitution in their lives compared with . % in the non-sexually abused/assaulted group. in addition, . % of sexual abuse/assault victims reported having injected drugs, compared with . % in the non-sexually abused/assaulted group. more statistical analyses will bring other significant factors to light, especially when we analyze separately those victim of childhood sexual abuse as compare to those victim of sexual assault after childhood. elucidating the risk factors for getting involved in hiv-risk-related behaviours is important for the development of comprehensive and appropriate prevention and treatment intervention strategies. introduction: new immigrants and refugees to canada frequently emigrate from regions of the world where intestinal parasitic infections with worms are endemic. of note, some of these parasites area capable of surviving for years to decades within a given host and can have life threatening consequences many years after initial infection. thus, early diagnosis and treatment of intestinal parasitic worms is considered important in high risk immigrant populations, however there remains a lack of consensus regarding the best method of accomplishing this. diagnosing worm infections through stool examinations is costly and has limited sensitivity, while presumptive treatment of all immigrants, although advocated by some, is expensive and results in healthy individuals being unnecessarily treated. herein, we examine the utility of a hematologic marker (i.e. peripheral blood eosinophilia) as a screening instrument to identify parasitic worm infections in new immigrants to toronto. we identified adults, years of age or older, who were screened for intestinal parasitic infections by stool examination as part of a recently developed screening protocol at a downtown toronto community health centre. we examined the prevalence of infections with worms and subsequently evaluated the impact of several demographic factors on the presence of worm infections. we also determined the sensitivity and specificity of peripheral blood eosinophilia (defined as greater than eosinophils per ml) as a marker for intestinal parasitic worm infections. results: overall, % of the immigrants tested had evidence of at least one worm infection on a single stool examination, while % of such individuals bad infections with multiple worms concurrently. age did not appear to be associated with the presence of worms, however % of males had evidence of worm infections compared with % of females (p= . ). immigrants from asia, sub-saharan africa, and central america had the highest burden of overall infection. the sensitivity and specificity of peripheral blood eosinophilia for worm infections was % and % respectively. conclusions: one in five recent immigrants presenting to a community health centre in downtown toronto had evidence of at least one intestinal parasitic worm infection. the highest burden of illness was in men and in those emigrating from less developed regions of the world. peripheral blood eosinophilia is a poor screening test for worm infections however its presence is highly suggestive of the existence of worms in new immigrants. more than a decade ago, the journal of american college health recommended that a national study be conducted to measure the health status of african american college students, 'both health disparities and [their] positive healthful behaviors' (fennell, ) . it was later decided that when exploring the level of health risk behaviors for african american students, gender is an important variable and should be included in the research (fennell, ) . at historically black college and universities (hbcus) college health researchers must tackle gender disparities through highly-effective health promotion and disease prevention programs. the purpose of this review is to examine the literature that addresses the overarching health behaviors (i.e. risky sexual behavior, poor diet, smoking, physical inactivity, etc.) of african american men who attend hbcus. despite the various social, cultural, and academic benefits of african american students who attend hbcus, the number of research studies that adequately address their health and health behaviors is limited. studies indicate that african american men who attend hbcus are actively engaged in poor health behaviors. compared to females at hbcus, african american men are more likely to behave in ways that could result in injuries and the use tobacco, alcohol, and ~ther dru~. the city of toronto has recently proposed to conduct a street count of the homeless. like proposals that have come before, this most recent proposal is controversial among many homeless advocates and service providers because it is perceived as intrusive, likely to undercount the target population, and unnecessary for addressing the problem. advocates of the count view it as necessary to gauge the scope of the problem and advise city leaders about how to most effectively direct resources ro.the various homeless services. this paper first reviews the history of efforts to count homeless populat ns m toronto, describing the motivations and arguments of people on both sides of the issue. second, the paper reviews the methodological complexities of counting homeless populations, describing approaches that use shelter-counts, administrative data and street observations. those interested in counts for toronto and elsewhere can benefit from this review of approaches that have been proposed and carried out in other municipalities. third, the paper proposes a new community-base d strategy that joins the skills of methodologists, local experts, and service providers to ensure a fair and accurate count. the method of systematic social observation avoids some of the problems of early counts by utilizing a repeated identification approach to minimize undercount bias. the method also has the advantage of involving and compensating homeless individuals for assisting with the street count estimates. the estimation approach can be implemented on a rolling basis throughout the year. drug transitions) is a multi-level study aimed at examining the associations between features of the urban environment and mental health, drug use, and risky sexual behaviors. research participants are being recruited in new york city (nyc) neighborhoods. an essential first step in the implementation of this study was to delineate boundaries for each target neighborhood that could then be used to establish sampling frames and as key units of analytic interest. although many neighborhood studies rely on pre-established definitions (e.g. those used for the census or administrative purposes), such definitions do not always reflect contemporary settlement patterns. we felt that street level observations were a neces· sary component of the definition process. methods: the procedures used to delineate neighborhoods were: ( ) development of census block maps of targeted areas; ( ) review of land use maps and census tract data to ensure, prior to going into the field, tha.t particular blocks are residential and likely to have sufficient population for recruitment purposes; and ( ) field vislts and observation in each of the targeted areas. field observations focused on: housing characteristics, including housing type and condition; characteristics of commercial areas, such as likely customer base (e.g. local or no~, socio-economic status and ethnicity of customers); pedestrian volume (including con· gregauons of people m parks and outside stores or residences); obstructions to pedestrian traffic (e.g. ma or thoroughfares, multi-block industry or institutions); and maintenance and use of open spaces. results: in making the final decisions regarding neighborhood boundaries and the inclusion or exclusion of particular. blocks, we considered a broad range of factors including evidence of homogeneity an~ heterogeneity (socmeconomic, ethnic, housing type, environmental) across blocks within and blocks ad acent to a nei.ghborhood, and across the sample neighborhoods; the potential for efficient recruit· ment of appropriate particip.ants (i.e. sufficient local pedestrian traffic); and boundaries used in reporting census data (s? that population data can be used in our analysis). . altho~gh utilization of field observations for neighborhood definitions is relatively time consuming (ap~~ox mately hours for a block area, with more diverse neighborhoods taking even longer), we annc p~t~ that it will substantially improve the quality and consistency of our data gath· ~rmg ~nd analyse~. spec f c e?'amples from neighborhoods defined through this process will be given dur· m~ this presentatmn. we will also discuss the merits and limitations of characterizing neighborhoods usmg street level observations. has been no consideration for how social networks are associated with sse. the objective of this study was to identify personal and social network characteristics associated with being a recipient of sse. in this cross-sectional study, idus who injected in the past months were recruited from syringe exchange programs in montreal, canada, between april and january . information on each participant and on the persons with whom contact had occurred in the past month were elicited using a structured, interviewer-administe red questionnaire. participants provided detailed demographic and drug use information on up to idu members with whom drugs or injecting materials were shared. using logistic regression, personal and network characteristics were examined in relation to receipt of sterile syringes. res.its: of idus, % reported receiving sterile syringes in the past month from another idu. the sample mean age was years (range - ), % male, % caucasian, and % cocaine injectors. in multivariate analyses adjusted for age and gender, recipients of sterile syringes were more likely than non-recipients to share drugs after preparation ( r= . ( . - . )), to require help or to have helped inject another idu (or= . ( . - . )), to have asked someone to get sterile syringes from a syringe exchange program (or= . [ . - . )), to lend syringes (or= . [ . - . ) ) and to use drug preparation water that was previously used by another iou ( r= . ( . - . ) ) during the past months. recipients also had a higher rate of change (p= . ) of idus in their drug injecting network during the past month. with respect to social networks, % ( / ) of idu network members were providers of sterile syringes and were more likely than non-providers to inject everyday (or= . ( . - . )). when stratified by their role as a sexual partner or as someone who provides support (e.g. friend, family member), further risk behaviours were observed in relation to sharing injecting materials with the participant. conclusion: recipients of sterile syringes and their idu network members had several high-risk behaviours for infection with bloodborne diseases. sse may afford an opportunity for the dissemination of other salutary behaviours such as information sharing on safe injecting practices between recipients and distributors. furthermore, drug injecting networks may be an avenue to reach idus who may not otherwise be exposed to preventive measures. there are numerous sources of stigma and labelling of mental and physical illness. first, the sociocultural dimension to stigma and labelling clearly influences patients, families, health care professionals and society's perception and treatment of illness. this creates multiple challenges related to illness identification and recovery, particularly in culturally diverse societies. second, the media is a major source of stigma and stereotyping with regard to a variety of mental and physical illnesses. despite increased public knowledge of many illnesses, studies have shown that stigma has intensified over the years in certain cases. a third element of stigma and labels appears with the use of diagnosis as a solution to human problems with the result that difficult to treat patients are repudiated and social issues are unaddressed. this presentation will serve to outline the development of stigma, various expressions of stigma, and consequences of stigma. it will provide some practical recommendations for the reduction of stigma related to mental and physical illness. purpose: to assess the knowledge, attitude, and practice about immunization for parent of - years old hispanic and african american children in los angeles county (lac). methods: we conducted two cluster surveys in lac. the sample was selected with probability proportionate to estimated size at the first stage and simple random sample of children at the second stage. data were collected through interview. we absuacted vaccine coverage data from immunization record card (irc) at home or from clinic records. the participation was % in hispanics and % in african americans populations. irc was not available at home for % of african american and % of hispanic children. results: all parents perceived their children got all necessary vaccine~. fa~orable attitudes to.w~rd immunization were reported by % of african american and % of h s?amc parents. '.he m~ ority of the parents ( % african american and % hispanic) agreed that vaccines prevent senous d se~ses among children. regarding vaccine safety, significantly more hispanic parents ( %) than african american parents ( %) mentioned that vaccines are safe. introduction: cervical cancer has been shown to be preventable by papanicolau tests in heterosexual women; however, the utility of papanicolau test in lesbians is controversial. cervical cancer is caused by the human papillomavirus (hpv) which is transmitted by sexual _intercourse; howev_er, its' transmission by homosexual intercourse is also controversial. the goal of this study was to review the evidence for papanicolau tests in lesbians. methods: a pub med, ovid ( ovid ( to , and cochrane library search was performed using the mesh headings "homosexuality , female," "vaginal smears," and "papillomavirus, human." in pub med, the clinical queries feature was used with "diagnosis" and "broad, sensitive" filters. a google advanced search of the internet was conducted with the terms "lesbian," "cervical cancer," and "pap rest." the url was limited to ".ca," ".edu," or ".gov." results: the search yielded original articles and reviews, but no cochrane reviews. none of the publications were canadian. website hits were found and selected websites were reviewed. studies showed that lesbians have fewer papanicolau tests than heterosexual women; however, many reported risk factors for cervical cancer, including multiple past or current sexual partners (male and female), early age of first coitus, history of sexually transmitted diseases, and cigarette smoking. hpv has been detected in - % of lesbians and - % of lesbians who have never had sex with men. case studies of abnormal papanicolau tests in lesbians who have never had sex with men have also been reponed. sexual transmission of hpv among lesbians can be explained by several factors: ) - % of lesbians have had sex with men and - % of lesbians continue to have sex with men. ) hpv may be transmitted by sexual behaviours among women, like digital-vaginal sex, digital-anal sex, oral sex, and the use of insertive sex toys. ) hpv transmission requires only skin-to-skin contact. genital hpv has been identified on human fingers. some professional organizations, like the society of obstetricians and gynecologists of canada and the american cancer society, recognize the need for papanicolau tests in lesbians. other organizations, like the canadian cancer society, do not have official policy statements. the current ontario cervical screening program does not specifically address lesbians. conclusion: although the data was limited, most studies recommended that lesbians should receive papanicolau tests. the frequency of these tests was controversial. policy makers and professional organizations should address the needs of this special population and make specific recommendations . monique chaaya, ahia sibai, hiam chemaitelly, and zana el roueiheb . literature concerning the mental and physical effect of work at an old age is contradictory. in addinon, urban environments are physically and socially harsh with reduced potential for income generation and employment and increased potential for depression. the present paper is an attempt to study how do work, or lack of work, link to the experience of depression among older adults in underprivileged lebanese urban communities. the data comes from a cross-sectional survey, where elderly residing in underprivileged communities in beirut, including a palestinian refugee camp, were successfully inter-v ewed through face-to-face interviews. logistic regression was performed to assess the effect of work on depression ad_justing for many other covariates. data showed that . % of people aged years and more were still workmg. there was a highly protective effect of work on depression in elderly males (or= . , % cl= . - . ). the current study is the first of its kind in the arab region and more work shou_ld be _don_e in this area. it is important for the lebanese government to consider elderly rights for social mclus n m terms of employment opportunities. amam nuru-jeter, nancy adler, and burton singer . l~u~on:_ the socioeconomic gradient is perhaps the most persistent and significant finding in social epidem ological research. the insistent nature of the ses effect is evidenced by its significance after acc?untmg for ~umerous confounds. the significance and magnitude of the effect, however, varies by ::•al group. evidence_ o_f the relative effect of race and ses is inconclusive. further, less attention has f ~ ptid to the specific interactions of race and ses than to examinations of which is a better predictor d ~ th. ~sues are further complicated by the explanatory complexity of the various measures of ses anl . owht ey relate to the health of various social groups. understanding the specific nature of these re a ons ips s necessary for guiding he ith d · i · · h a an soc a po mes and programs aimed at improving t e poster sessions v health of our most disadvantaged groups, and therefore population health, overall. this study examines the synergistic effects of ses with both race and gender in predicting group differences in mortality. methods: analyses use data from the national longitudinal mortality survey (n= , ) for the years , , and - ; and were linked to the national death index for deaths occurring through . results were confirmed using data from the national mortality followback survey for people who died in (n= , ) and the national health interview survey (denominator). we used correlation analysis and the standardized mortality ratio to examine ses (education and income), race, and gender as predictors of group differences in changes in mortality. results: for the total population, analyses support the income gradient showing significant declines in mortality ratios from low to high income along the income strata. education shows a significant drop in mortality with completion of high school and completion of college, exhibiting a threshold rather than a gradient effect. compared to whites, blacks receive diminishing health returns for each subsequent level of income and education; with whites closely mirroring the total population in ses thresholds. similarly, compared to men, women do not experience the same health gains at comparable ses levels. for education, black men and women only show significant mortality declines upon completion of high school. the ses gradient operates differently among race and gender subgroups. threshold effects suggest resource gains in life opportunities at particular milestones along the ses gradient. further, ses matters less for blacks and women compared to whites and men suggesting differing implications for health and social policy aimed at reducing disparities. objective: we assessed the impact of diabetes in a large puerto rican community of chicago by measuring the prevalence of diagnosed diabetes and calculating the diabetes mortality rate. methods: we analyzed data from a comprehensive health survey conducted in randomly selected households in community areas. questions on diagnosed diabetes and selected risk factors were asked. in addition, mortality data were analyzed in order to calculate the age-adjusted diabetes mortality rate. when possible, rates were compared to those found in other studies. results: the diabetes prevalence located in this community ( . %: % cl= . %- . %) is one of the highest ever reported for puerto ricans. for instance, it is more than three times higher than the prevalence for the us ( . %) and twice the prevalence for puerto ricans in new york ( . %) and puerto rico ( . %- . %). diagnosed diabetes was found to be significantly associated with obesity (p= . ). the prevalence was particularly high among older people, females, those horn in the us, and those with a family history. the diabetes mortality rate ( . per , population) was more than twice the rate for all of chicago ( . ) and the us ( . ). conclusions: understanding why the diabetes and mortality rates for puerto ricans in this commu· nity are so much higher than those of other communities is imperative. collaboration between researchers, service providers and community members can help address the issues of diabetes education, early screening and diagnosis and effective treatment needed in this community. introduction: sars is a respiratory illness that is spread from person to person through dose contact. this infectious disease outbreak was unusual due to the high rate of infection among health care workers. the aim of the study is to explore the demographic and attitudinal determinants of psychological distress due to sars among health care workers of a toronto hospital. methods: a total of adult participants completed questionnaires co assess psychological distress (impact of event scale -jes) and attitudes to sars. of these, participants completed the questionnaire during the sars i outbreak, and participants completed the questionnaire during the sars ii outbreak. participants also provided information on demographic variables, including occupation and exposure to sars. principal components analysis was used to derive eight attitudinal scales: fear: system, protection, prevention, job stress, stigma, instrumental coping, and psychological copm~. l ear regression analyses were applied to evaluate the associations of the demographic and amtudmal variables, as well as time, with psychological distress. . . regression analyses showed that time and higher scores on fear, ob stress, stigma'. and instrumental coping were associated with a higher total ies score: (r =. ). contrary to expectations, none of the demographic variables was associated with total ies score. conclusion: the presence of psychological distress in health care workers is indicative of intrusive or avoidant responses to thoughts, feelings, and memories associated with the sars outbreak. this study shows that ( ) fear for one's health and the he~lth of.others, ( ) ex~erien~in~ job stress, ( )_tbe per· ception of stigma, ( ) usage of instrumental copmg skills, ~n~ ( ) t m_e s grufi~an~ly c~nmb~te to increased psychological distress in health care workers. potential mterventmns during mfecttous diseaie outbreaks in health care settings should be targeted to minimize the impact of these factors. purpose: the purpose of this study was to expand knowledge regarding feeding practices, know!· edge and nutritional beliefs of mothers currently residing in the dominican republic (dr). the rising incidence of obesity in children is a major national health concern and obesity in first and second-generation immigrant children also continues to rise. we know that parents (particularly mothers) shape children's early diet patterns and that immigrant mothers experience additional challenges related to acculturation and assimilation into a new culture, however there is a paucity of literature concerning the effect of immigrant adaptation to american culture on the nutrition of children. in addition, new immigrant knowledge about the causes of obesity and the resulting health implications for childhood obesity has not been assessed and reported. this qualitative study used focus group methodology to discuss views and practices related to the introduction of food for infants and feeding practices for young children, along with a discussion on knowledge and beliefs related to the causes and health implications of child· hood obesity. ten dominican mothers' of young children (birth to years old) who reside in a small town in the western frontier area of the dr were participants in the focus group. results from this srudy will be compared to results from an identical study that will be conducted in fall with new immi· grant mothers from the dr to the boston area. we will compare feeding practices, beliefs and knowledge about nutrition for young children between these two groups. methods: using participatory principles, a focus group design was used to interview a group of mothers in the dr. the investigator along with a bilingual translator conducted the focus group. the session was tape recorded and is currently in the process of being transcribed and translated. transcribed data will be systematically analyzed themes will be identified. a qualitative data analysis software will be used to organize and code the data according to the specific aims of the study. supporting quotations will be selected to substrate each theme. lmpli~tions for urban health practice: an ultimate goal of this study is to lay a foundation for understanding the process of acculturation on feeding practices of mothers when they immigrate to the us. understanding beliefs, knowledge and feeding practices that mothers use with young children will help m ~he ~evelopment of culturally and linguistically appropriate educational strategies and materials for use m primary prevention of pediatric obesity. in canada more than seventy-five percent of immigrants choose to stay in three major urban centers of toronto, montreal and vancouver. approximately fifty percent of the immigrants eventually set· tie m ~~e greater tor<_>nto area. there is mounting evidence that the increasing immigrant population has a_ sigmfic~nt health disadvantage over canadian-born residents. this health disadvantage manifests particularly m the ma "ority of "mm "gr t h h d be · · h . . . . an s w o a en m canada for longer than ten years. this group as ~n associ~te~ with higher risk of chronic disease such as cardiovascular diseases. this disparity twccb n ma onty of the immigrant population and the canadian-born population is of great importance to ur an health providers d" · i i · b as isproporttonate y arge immigrant population has settled in the ma or ur an centers. generally the health stat f · · · · · · h h been . us most mm grants s dynamic. recent mm grants w o av_e ant •;ffca~ada _for less ~han ~en years are known to have a health advantage known as 'healthy imm • ~ants r::r · ~:s eff~ ~ defined by the observed superior health of both male and female recent immi- immigrant participation in canadian society particularly the labour market. a new explanation of the loss of 'healthy immigrant effect' is given with the help of additional factors. lt appears that the effects of social exclusion from the labour market leading to social inequalities first experienced by recent immigrant has been responsible for the loss of healthy immigrant effect. this loss results in the subsequent health disadvantage observed in the older immigrant population. a study on patients perspectives regarding tuberculosis treatment by s.j.chander, community health cell, bangalore, india. introduction: the national tuberculosis control programme was in place over three decades; still tuberculosis control remains a challenge unmet. every day about people die of tuberculosis in india. tuberculosis affects the poor more and the poor seek help from more than one place due to various reasons. this adversely affects the treatment outcome and the patient's pocket. many tuberculosis patients become non-adherence to treatment due to many reasons. the goal of the study was to understand the patient's perspective regarding tuberculois treatment provided by the bangalore city corporation. (bmc) under the rntcp (revised national tuberculosis control programme) using dots (directly observed treatment, short course) approach. bmc were identified. the information was collected using an in-depth interview technique. they were both male and female aged between - years suffering from pulmonary and extra pulmonary tuberculosis. all patients were from the poor socio economic background. results: most patients who first sought help from private practitioners were not diagnosed and treated correctly. they sought help form them as they were easily accessible and available but they. most patients sought help later than four weeks as they lacked awareness. a few of patients sought help from traditional healers and magicians, as it did not help they turned to allopathic practitioners. the patients interviewed were inadequately informed about various aspect of the disease due to fear of stigma. the patient's family members were generally supportive during the treatment period there was no report of negative attitude of neighbours who were aware of tuberculosis patients instead sympathetic attitude was reported. there exists many myth and misconception associated with marriage and sexual relationship while one suffers from tuberculosis. patients who visited referral hospitals reported that money was demanded for providing services. most patients had to borrow money for treatment. patients want health centres to be clean and be opened on time. they don't like the staff shouting at them to cover their mouth while coughing. conclusion: community education would lead to seek help early and to take preventive measures. adequate patient education would remove all myth and conception and help the patients adhere to treatment. since tb thrives among the poor, poverty eradiation measures need to be given more emphasis. mere treatment approach would not help control tuberculosis. lntrod#ction: the main causative factor in cervical cancer is the presence of oncogenic human papillomavitus (hpv). several factors have been identified in the acquisition of hpv infection and cervical cancer and include early coitarche, large number of lifetime sexual partners, tobacco smoking, poor diet, and concomitant sexually transmitted diseases. it is known that street youth are at much higher risk for these factors and are therefore at higher risk of acquiring hpv infection and cervical cancer. thus, we endeavoured to determine the prevalence of oncogenic hpv infection, and pap test abnormalities, in street youth. ~tbods: this quantitative study uses data collected from a non governmental, not for profit dropin centre for street youth in canada. over one hundred females between the ages of sixteen and twentyfour were enrolled in the study. of these females, all underwent pap testing about those with a previous history of an abnormal pap test, or an abnormal-appearing cervix on clinical examination, underwent hpv-deoxyribonucleic (dna) testing with the digene hybrid capture ii. results: data analysis is underway. the following results will be presented: ) number of positive hpv-dna results, ) pap test results in this group, ) recommended follow-up. . the results of this study will provide information about the prevalence of oncogemc hpv-dna infection and pap test abnormalities in a population of street youth. the practice implic~ tions related to our research include the potential for improved gynecologic care of street youth. in addition, our recommendations on the usefulness of hpv testing in this population will be addressed. methods: a health promotion and disease prevention tool was developed over a period of several years to meet the health needs of recent immigrants and refugees seen at access alliance multicultural community health centre (aamchc), an inner city community health centre in downtown toronto. this instrument was derived from the anecdotal experience of health care providers, a review of medical literature, and con· sultations with experts in migration health. herein we present the individual components of this instrument, aimed at promoting health and preventing disease in new immigrants and refugees to toronto. results: the health promotion and disease prevention tool for immigrants focuses on three primary health related areas: ) globally important infectious diseases including tuberculosis (tb), hiv/aids, syphilis, viral hepatitis, intestinal parasites, and vaccine preventable diseases (vpd), ) cancers caused by infectious diseases or those endemic to developing regions of the world, and ) mental illnesses includiog those developing among survivors of torture. the health needs of new immigrants and refugees are complex, heterogeneous, and ohen reflect conditions found in the immigrant's country of origin. ideally, the management of all new immigrants should be adapted to their experiences prior to migration, however the scale and complexity of this strategy prohibits its general use by healthcare providers in industrialized countries. an immigrant specific disease prevention instrument could help quickly identify and potentially prevent the spread of dangerous infectious diseases, detect cancers at earlier stages of development, and inform health care providers and decision makers about the most effective and efficient strategies to prevent serious illness in new immigrants and refugees. lntrodmction: as poverty continues to grip pakistan, the number of urban street children grows and has now reached alarming proportions, demanding far greater action than presently offered. urbanization, natural catastrophe, drought, disease, war and internal conflict, economic breakdown causing unemployment, and homelessness have forced families and children in search of a "better life," often putting children at risk of abuse and exploitation. objectives: to reduce drug use on the streets in particular injectable drug use and to prevent the transmission of stds/hiv/aids among vulnerable youth. methodology: baseline study and situation assessment of health problems particularly hiv and stds among street children of quetta, pakistan. the program launched a peer education program, including: awareness o_f self and body protection focusing on child sexual abuse, stds/hiv/aids , life skills, gender and sexual rights awareness, preventive health measures, and care at work. it also opened care and counseling center for these working and street children ar.d handed these centers over to local communities. relationships among aids-related knowledge and bt:liefs and sexual behavior of young adults were determined. rea.sons for unsafe sex included: misconception about disease etiology, conflicting cultural values, risk demal, partner pressur~, trust and partner significance, accusation of promiscuity, lack of community endorsement of protecnve measures, and barriers to condom access. in addition socio-economic pressure, physiological issues, poor community participation and anitudes and low ~ducation level limited the effectiveness of existing aids prevention education. according to 'the baseline study the male children are ex~ to ~owledge of safe sex through peers, hakims, and blue films. working children found sexual mfor~anon through older children and their teachers (ustad). recommendation s: it was found that working children are highly vulnerable to stds/hiv/aids, as they lack protective meas":res in sexual abuse and are unaware of safe sexual practices. conclusion: non-fatal overdose was a common occurrence for idu in vancouver, and was associated with several factors considered including crystal methamphetamine use. these findings indicate a need for structural interventions that seek to modify the social and contextual risks for overdose, increased access to treatment programs, and trials of novel interventions such as take-home naloxone programs. background: injection drug users (idus) are at elevated risk for involvement in the criminal justice system due to possession of illicit drugs and participation in drug sales or markets. the criminalization of drug use may produce significant social, economic and health consequences for urban poor drug users. injection-related risks have also been associated with criminal justice involvement or risk of such involvement. previous research has identified racial differences in drug-related arrests and incarceration in the general population. we assess whether criminal justice system involvement differs by race/ethnicity among a community sample of idus. we analyzed data collected from idus (n = , ) who were recruited in san francisco, and interviewed and tested for hiv. criminal justice system involvement was measured by arrest, incarceration, drug felony, and loss/denial of social services associated with the possession of a drug felony. multivariate analyses compared measures of criminal justice involvement and race/ethnicity after adjusting for socio-demographic and drug-use behaviors including drug preference, years of injection drug use, injection frequency, age, housing status, and gender. the six-month prevalence of arrest was highest for whites ( %), compared to african americans ( %) and latinos ( % ), in addition to the mean number of weeks spent in jail in the past months ( . vs. . and . weeks). these differences did not remain statistically significant in multivariate analyses. latinos reported the highest prevalence of a lifetime drug felony conviction ( %) and mean years of lifetime incarceration in prison ( . years), compared to african americans ( %, . years) and whites ( %, . years). being african american was independently associated with having a felony conviction and years of incarceration in prison as compared to whites. the history of involvement in the criminal justice system is widespread in this sample. when looking at racial/ethnic differences over a lifetime including total years of incarceration and drug felony conviction, the involvement of african americans in the criminal justice system is higher as compared to whites. more rigorous examination of these data and others on how criminal justice involvement varies by race, as well as the implications for the health and well-being of idus, is warranted. homelessness is a major social concern that has great im~act on th~se living.in urban commu?ities. metro manila, the capital of the philippines is a highly urbanized ar~ w. t~ the h gh~st concentration of urban poor population-an estimated , families or , , md v duals. this exploratory study v is the first definitive study done in manila that explores the needs and concerns of street dwdlent\omc. less. it aims to establish the demographic profile, lifestyle patterns and needs of the streetdwdlersindit six districts city of manila to establish a database for planning health and other related interventions. based on protocol-guid ed field interviews of street dwellers, the data is useful as a template for ref!!. ence in analyzing urban homelessness in asian developing country contexts. results of the study show that generally, the state of homelessness reflects a feeling of discontent, disenfranchisem ent and pow!!· lessness that contribute to their difficulty in getting out of the streets. the perceived problems andlar dangers in living on the streets are generally associated with their exposure to extreme weather condirioll! and their status of being vagrants making them prone to harassment by the police. the health needs of the street dweller respondents established in this study indicate that the existing health related servias for the homeless poor is ineffective. the street dweller respondents have little or no access to social and health services, if any. some respondents claimed that although they were able to get service from heallh centers or government hospitals, the medicines required for treatment are not usually free and are beyond their means. this group of homeless people needs well-planned interventions to hdp them improve their current situations and support their daily living. the expressed social needs of the sucet dweller respondents were significantly concentrated on the economic aspect, which is, having a perma· nent source of income to afford food, shelter, clothing and education. these reflect the street dweller' s need for personal upliftment and safety. in short, most of their expressed need is a combination of socioeconomic resources that would provide long-term options that are better than the choice of living on the streets. the suggested interventions based on the findings will be discussed. . methods: idu~ aged i and older who injected drugs within the prior month were recruited in usmg rds which relies on referral networks to generate unbiased prevalence estimates. a diverse and mon· vated g~o~p of idu "seeds." were given three uniquely coded coupons and encouraged to refer up to three other ehgibl~ idu~, for which they received $ usd per recruit. all subjects provided informed consent, an anonymous ~t erv ew and a venous blood sample for serologic testing of hiv, hcv and syphilis anti~!· results. a total of idus were recruited in tijuana and in juarez, of whom the maion!)' were .male < .l. % and . %) and median age was . melhotls: using the data from a multi-site survey on health and well being of a random sample of older chinese in seven canadian cities, this paper examined the effects of size of the chinese community and the health status of the aging chinese. the sample (n= , ) consisted of aging chinese aged years and older. physical and mental status of the participants was measured by a chinese version medical outcome study short form sf- . one-way analysis of variance and post-hoc scheffe test were used to test the differences in health status between the participants residing in cities representing three different sizes of the chinese community. regression analysis was also used to examine the contribution of size of the chinese community to physical and mental health status. rmdts: in general, aging chinese who resided in cities with a smaller chinese population were healthier than those who resided in cities with a larger chinese population. the size of the chinese community was significant in predicting both physical and mental health status of the participants. the findings also indicated the potential underlying effects of the variations in country of origin, access barriers, and socio-economic status of the aging chinese in communities with different chinese population size. the study concluded that size of an ethnic community affected the health status of the aging population from the same ethnic community. the intra-group diversity within the aging chinese identified in this study helped to demonstrate the different socio-cultural and structural challenges facing the aging population in different urban settings. urban health and demographic surveillance system, which is implemented by the african population & health research center (aphrc) in two slum settlements of nairobi city. this study focuses on common child illnesses including diarrhea, fever, cough, common cold and malaria, as well as on curative health care service utilization. measures of ses were created using information collected at the household level. other variables of interest included are maternal demographic and cultural factors, and child characteristics. statistical methods appropriate for clustered data were used to identify correlates of child morbidity. preliminary ratdts: morbidity was reported for , ( . %) out of , children accounting for a total of , illness episodes. cough, diarrhoea, runny nose/common cold, abdominal pains, malaria and fever made up the top six forms of morbidity. the only factors that had a significant associ· ation with morbidity were the child's age, ethnicity and type of toilet facility. however, all measures of socioeconomic status (mother's education, socioeconomic status, and mother's work status) had a significant effect on seeking outside care. age of child, severity of illness, type of illness and survival of father and mother were also significantly associated with seeking health care outside home. the results of this study have highlighted the need to address environmental conditions, basic amenities, and livelihood circumstances to improve child health in poor communities. the fact that socioeconomic indicators did not have a significant effect on prevalence of morbidity but were significant for health seeking behavior, indicate that while economic resources may have limited effect in preventing child illnesses when children are living in poor environmental conditions, being enlightened and having greater economic resources would mitigate the impact of the poor environmental conditions and reduce child mortality through better treatment of sick children. inequality in human life chances is about the most visible character of the third world urban space. f.conomic variability and social efficiency have often been fingered to justify such inequalities. within this separation households exist that share similar characteristics and are found to inhabit a given spatial unit of the 'city. the residential geography of cities in the third world is thus characterized by native areas whose core is made up of deteriorated slum property, poor living conditions and a decayed environment; features which personify deprivation in its unimaginable ma~t~de. there are .eviden~es that these conditions are manifested through disturbingly high levels of morbidity and mortality. ban · h h d-and a host of other factors (corrupt n, msens t ve leaders p, poor ur ty on t e one an , . · f · · · th t ) that suggest cracks in the levels and adherence to the prmc p es o socta usnce. ese governance, e c . . . . . ps £factors combine to reinforce the impacts of depnvat n and perpetuate these unpacts. by den· grou o . · "id . . bothh tifying health problems that are caused or driven by either matena _or soc a e~nvanon or , t e paper concludes that deprivation need not be accepted as a way. of hfe a~d a deliberate effon must be made to stem the tide of the on going levels of abject poverty m the third world. to the extent that income related poverty is about the most important of all ramifications of po~erty, efforts n_iu_st include fiscal empowerment of the poor in deprived areas like the inner c~ty. this will ~p~ove ~he willingness of such people to use facilities of care because they are able to effectively demand t, smce m real sense there is no such thing as free medical services. ). there were men with hiv-infection included in the present study (mean age and education of . (sd= . ) and . (sd= . ), respectively). a series of multiple regressions were used to examine the unique contributions of symptom burden (depression, cognitive, pain, fatigue), neuropsychologic al impairment (psychomotor efficiency), demographics (age and education) and hiv disease (cdc- staging) on iirs total score and jirs subscores: ( ) activities of daily living (work, recreation, diet, health, finances); ( ) psychosocial functioning (e.g., self-expression, community involvement); and ( ) intimacy (sex life and relationship with partner). resnlts: total iirs score (r " . ) was associated with aids diagnosis (ii= . , p < . ) and symptoms of pain (ii= - . , p < . ), fatigue (ji = - . , p < . ) and cognitive difficulties (p = . , p < . ). for the three dimensions of the iirs, multiple regression results revealed: ( ) activities of daily living (r = . ) were associated with aids diagnosis (ii = . , p < . ) and symptoms of pain <p =- j , p < . ), fatigue (ji = - . , p < . ) and cognitive difficulties (ji = . , p < . ); ( ) psychosocial functioning (r = . ) was associated with was associated with symptoms of fatigue (ii= - . , p < . ) and cognitive difficulties <ii = . , p < . ); and ( ) intimacy (r = . ) was related to was associated with symptoms of fatigue (ij = - . , p < . ) and cognitive difficulties (ii= . , p < . ). methods: the sif evaluation methodology involves a comprehensive database located at the sif, a randomly selected p~o.spective coh~rt of sif users, and two pre-existing external control cohorts. . . ~ts: in addmon to reporting process data and descriptions of the sif users, we report on data indicating that the establishment of the sif has been independently associated with reductions in public ~':°g ~ (p <?. ), and syringe sharing (aor = . [ %ci: . _ . ); p = . ) and other unsafe m ecnon pract _ces_ (p ~ . ), and increased uptake of detox services (log-rank p = . ). as well, we report on da~ md cat ng that the sif has not prompted adverse changes in community drug use patterns. the vancouver sif has been well accepted by the target population, and while adve~ events s~c~ as overdoses have occurred, these events have been successfully managed. externally compiled data indicate that the sif has been associated with substantial declines in public disorder !'oster sessions v associated with injection drug use, syringe sharing, and increased uptake of detox services. as well, the establishment of the sif has not exacerbated community drug use patterns. ongoing evaluation activities wiu involve assessing the impact of the sif on a variety of outcomes, including infectious disease transmission, fatal overdose, and utilization of health and social services. city, brazil, - maria cristina almeida, waleska caiaffa, renato assum;iio, and fernando proietti dengue cases were described according to time, space, intensity, age, gender, onset of symptoms, residence address and census tract. spatial distribution of two groups (children and women over years old and men aged - ) were compared, under assumption that they have distinct behaviors regarding their displacement around the city. analysis included local moran index, ripley\\'s k function and recurrence of census areas over time. about , cases were identified in seven epidemic waves. concentration of cases in small areas, followed by a spread either in space or time suggested endemic patterns. regarding age-gender groups, distinct patterns suggested that residence might not be a good proxy in determining the local of infection for men aged - . dengue is shifting to endemic pattern in this city and transmission may not be sole related to home environment, suggesting that additional spatial information must be couected aiming efficient control measures. murukan kandamuthan and subodh kandamuthan lnl uduction: illness or disablement of a child may affect the economic functioning of a family as it alters the employment pattern and earnings of parents this paper tries to assess the health status and the quality of life of disabled children, and how generally, severe disablement in a child affected their fami-lies\' finances, and to quantify any such effects the problems faced by children in their home and to provide information relevant to the formation of criteria for new or increased cash support. methods: a case-control study was done in the thiruvananthapuram district, capital city of kerala by selecting a random sample of families with severely disabled children below years and a random sample of normal children matched for age and occupation of the parents. comparative and subjective data were collected. money spent on children\'s medical care, loss of earnings of the parents, and other economic burden to the family due to the disability of the child in the family. a discriminant analysis along with univariate analysis was done to assess the factors that mostly differentiate the disabled and normal children. the mean expenditure of the families with a disabled child was rs. /-per month, which is significantly higher than the corresponding expenditure of rs. /-per month of families with normal child, (t= . , p <. ). of the disabled children, % were not getting any social security payments and % had no special concessions for medical and other educational purposes. the analysis of income and expenditure pattern indicated that financial impact of disablement in a child on the family is significant. the discriminant model results revealed that medical expenditure was a significant variable that differentiated the disabled and normal child. the study found that the health status and quality of life of the disabled children were far from satisfactory. this in fact affected the economic status of the disabled children. in addition to reduced earnings, there are extra costs for disabled children for travel, domestic help, medical care, and health care expenditures (hospital care, physician services, dentistry, drugs and others) for disabled individuals. a strong case can be made for their long-term care by improving the financial support to such families possibly through the introduction of an allowance specially to compensate for the earnings lost by parents due to the disability of their children. widows in india are considered disadvantage group of population. because they are characterized by pangs of separation from spouse, and consequently they go through mental agony, social ~s?lation, and economic dislocation. in addition to these, poverty, landlessness, homelessness, malnutr non etc. endure serious deterioration of their health. according to census , there are million women are widowed and one fourth live in urban areas. there is a noticeable increase of urban widows from the previous census (almost half). the paper examines the type of disability and chronic ailment borne among elderly widows ( years and above). fifty second round of national sample survey aske~ the individuals three sets of questions regarding their health: their status of health, whether they are physically poster sessions v immobile, and whether or not they have had any specific chronic illnesses. although health infrastruc- · ble ·n urban setting in india as compared to rural counterpart, prevalence of tures are arge y ava a . . . . . h · · · h h"gher "n urban areas analysis shows omt problems m old age qmte common c romc ness is muc • . . and nearly percent elderly widows are suffering from this ail'. ent in urban areas. one-fifth of widows are suffering from high/low bp. heart disease, diabetes and urinary problems are much ~ore pre~alent in urban areas though disabilities is comparatively lower in urban areas. however, the d~fference is not statistically significant. disability with respect to vision is more pronounced and one third_ of the total respondents have problems regarding eyesight. one fifths ofdderly widows are _ha.rd of hearing. though disability increases with age, similar trend is not observed with respect to chr~mc illness. the percepnon of self-health among elderly becomes poorer as their age increases. the perceived health status need not be always corrected to objective indicators of health. it is noted that around per~en~ of those perceived their health as "excellenr" or "very good" are found to be suffering from chrome disease of omts and percent have visual disability. to conclude an elderly widow living in urban areas have similar health problems as she jives in rural areas. this can be easily explained, as they were not made aware to seek treatment from health facility. in addition, the study shows that the economic conditions are deterrent factors for their illness. it is essential that intervention should be taken up improving their economic conditions so that wellbeing of this most vulnerable group of the society can be taken care of. heart failure is a disease that affects nearly million people world wide. the united states alone accounts for one third of this population. blacks are stricken with heart failure twice as often as whites. men are more likely to develop chf than women, however since the majority of the chf population are seniors, there are actually more women than men. congestive heart failure (chf) has become a pandemic. as the baby boomer generation ages, the number of chf cases will rise dramatically. (young, j. & mills, r., ). after the age of , each proceeding decade doubles the incidence level of chf. the average person has a in chance of developing heart failure within their lifespan according to the framingham study (nih.gov). individuals aging or older compose over half of the entire documented heart failure population. in this age group, chf is the leading cause of hospitalization. many patients are continuously readmitted. it is estimated that the chf population will increase by one million within the next years. mortality was at % for a two year period and % for five years (young, j. & mills, r., ). data from: aha as technology evolves, the understanding of the nature of heart failure has become clearer. in the beginning of the th century heart failure was diagnosed as a condition that presented with edema (swelling) in the extremities caused by water retention. treatment in the beginning of the past cenrury was limited to abdominal drainage and diuretics. the discovery of the heart's insufficient pumping ability in heart failure patients lead to new surgeries and devices such as heart transplants and ventricular assist devices (bridge until transplant is available). ventricular hypertrophy often occurs before the development of heart failure. hypertrophy is the term given for cardiac remodeling. cardiac remodeling also includes chamber dilation (young, j. & mills, r., ) . chf financial burden the us healthcare financing administration has ranked chf as the highest cost illness in the diagnose-related area. direct costs related to chf in the us for were nearly $ billion. these costs included hospital admissions, physician fees, home health aids and medications. indirect costs were over $ billion in . loss of jobs or death due to chf was the criteria for this category (young, j. & mills, r., ). . introduction: the injection drug user quality of life scale (iduqol) is a relatively new scale ~es gned to capture the unique and individual circumstances that determine quality of life among injection drug users (idus). the life areas comprising the instrument were based on the research literature an~ ~ocus group discussions with idus. the purpose of the present study was to evaluate the content validity of t.h~ iduqol using judgmental methods based on subject matter experts' (smes) ratings. content vah~ ty refers to the de~ee to which elements of an assessment tool are representative of the construct of interest and appropnate for a given population. methods: data were obtained from six smes, from the field of idu research and practice, who ~ere. asked t.o evaluate various aspects of the iduqol, including the title of the instrument, administraon instruchons, clarity of the names and descriptions of each life area, response format, scoring instruc-no~s and examples, record form and whether each life area should be included in the instrument. sme ratings were made using either or point scales. sm es were also given the opportunity to comment on poster sessions v each section and to suggest whether important life areas had been overlooked, were redundant, not relevant, or in need of revision. (cvi) and the ~v.erage ~eviation index (ad) were used to evaluate smes' agreement on ratings of the content vahd ty vanables. both measures provided support for the content validity of various aspects of the iduqol, although results from the stricter ad index noted some areas of disagreement, including the description of particular life areas (e.g., being useful, drugs, sex), the inclusion of some life areas (e.g., drug treatment, education, independence and free choice), and the ease of the scoring instructions. the findings from this study provide (a) content validity evidence to support the use of the iduqol as well as (b) recommendations to suengthen both the instrument (e.g., improved descriptions for some items) and the accompanying administration and scoring manual (e.g., an easier scoring template). changes made to the instrument and its manual make the iduqol even easier for researchers, practitioners, and program evaluators to use as a way of assessing, and tracking changes over time or as a result of interventions in, quality of life in injection drug users. introduction: strict adherence to prescribed regimens is required to derive maximal benefit from highly active antireuoviral therapy (haart) in persons living with hiv/aids (phas). adherence is a key determinant of the degree and durability of viral suppression. adherence is also essential in reducing the spread of hiv and ensuring that today's treatments remain effective for as long as possible. the objective of this study is to conduct a systematic review of the research literature on the effectiveness of education and patient support strategies for improving adherence to haart. methods: a systematic search of the core databases was performed from january until may . randomized controlled trials examining the effectiveness of education and patient support interventions to improve the adherence to haart were considered for inclusion. only those studies that measured adherence at a minimum of six weeks were included. study selection, quality assessments, and data abstraction were performed independently by two reviewers. results: study heterogeneity with respect to differing populations, interventions, outcomes, and length of follow-up did not allow for meta-analysis. we included studies involving , ph as. sample sizes ranged from to . study duration ranged from a single session to a variable number of sessions delivered over one year. many of the interventions involved the provision of an educational component to improve adherence and often addressed strategies to overcome barriers to adherence and the development of problem-solving skills. they ranged from simple interventions (e.g., the provision of reminder devices) to complex interventions (e.g., cognitive-behavioural therapy delivered by licensed psychologists). eleven of the studies demonstrated a statistically significant advantage associated with the described adherence intervention. the advantage associated with adherence outcomes does not seem to translate into the more clinically relevant outcome of viral suppression. only out of studies that reported virological or immunological results found a significant effect associated with the intervention. the studies had several methodological shortcomings. conclusions: there is a need for standardization and methodological rigour in the conduct of adherence trials. some interventions may have a significant impact on improving adherence. further research is required before any specific adherence improving strategy can confidently be incorporated into standard clinical practice. focus groups were used to collect data from a purposive sample of treatmentexperienced participants. focus group data were analyzed using a grou~ded t~eory appr~ach. i:ne themes identified from the interviews were used to identify the effects of ant rerrov rals on quality of hfe. the content of the mos-hiv was appraised against the themes identified from our analysis. participants also completed the mos-hiv survey and were asked whether the survey covered all important aspects of quality of life on antiretroviral medications. results: five key informant interviews and five focus groups with participants were used to identify effects on quality of life that are not directly ~aptu~ed by_ the mos-hiv health survey. our~~ showed that our participants described quality of hfe as mvol~mg_ a set of ~rsonal trad~ffs ~stay alive. in most cases, worsened quality of life was traded-off for gams ~ longevlty from ~~canon use. these eff~'ts or tradeoffs included: ( ) downstream consequences of side effects and toxlanes; ( ) loss of lrufe. pende~t decision-making privileges, ( ) having to choose drugs over ~areer; (~)burden of medication-taking responsibilities; and ( ) living life under a pretense and havmg to hide-the net effect of the tradeoffs, or "prices" to pay led to what was described as "longevity with hn without hope and future~. conclusion: our study highlights five major themes summarizing the impact of haart on quality on life, and suggests that currently used scales for measuring quality of life do not a~atd~ cap~e these findings and the associated consequences. the conceptual framework for measuring quality of bfe in hiv should be reconsidered in order to better capture the important effects of the medications on quality of life. this may involve widening the boundaries of the definition of health-related quality oflife to include aspects such as finances, employment, and housing. we should further consider the development of a haart adverse effect specific instrument, using a broad definition of adverse effect in order to capture all types of adverse impacts of hiv treatments on quality of life. introduction: measles (rubeola) is the most contagious vaccine preventable disease of humans. while cases of measles are uncommon in canada today, the disease continues to be a leading cause of morbidity and death in the developing world. as a result of human migration, measles cases still occur in canada, primari~ among immigrants, returning travelers, and other susceptible groups. canada's national advisory council on immunizations (naci) recommends that immigrants without records of measles immunization be considered for vac:cination since these individuals may not have been appropriately vaccinated in their native country. on rhe other hand, natural immunity to measles in immigrants is likely to be high given the high incidence of disease in developing parts of rhe world. thus it remains unclear if the most efficient strategy to achieve high levels of measles immunity in immigrants should entail initial serologic screening followed by vaccination of susceptible individuals or preemptive vaccination of all persons lacking immunization records. understanding the epidemiology of measles immunity in immigrant populations could help guide such decisions. . methods: we identified adults, years of age or older, who were screened for serologtc immunity to measles as part of a recently developed screening protocol at a downtown toronto community health centre. we subsequently determined if these individuals had any immunization records from their native country or from within canada. we then examined the relationship between several demographic factors and immunity to measles. results: % of immigrants had no prior immunization records. overall, % of the immigrants rested for immunity to measles were found to be immune; % of those under the age of , % of those between and years of age, % of those between and years of age, and % of those years of age or older. gender, education status, household income, and immigration status were nor ~ssoc ated wirh immunity to measles. immunity to measles was lowest among immigrants from eastern europe ( ~%), whil~ immigrants from other regions of the globe had greater than % immunity. c~lusrons: immigrants and refugees appear to have reasonably high levels of immunity to mea· sics, possibly related to natural infection wirh the measles virus. immigrants from eastern europe appear to have slightly. lower l~vel~ of immunity to the measles virus. universal screening for immunity to meales or preemptive vac:cmauon may both be inefficient public health strategies, however further research is needed to corroborate these findings. nancy r~ss, stephane tremblay, saeeda khan, daniel crouse, mark tremblay, and jean-marie berrhelor o~ve: the speed of the rise in obesity in places like canada suggests that rather than a shift in the gcncnc_ com~sirion of the population, the root of the obesity pandemic is an environment that suprrs ~besity. this paper examines the influence of neighbourhood and metropolitan characteristics. bour~lts:. while accounting. for individual socio-demographics and behaviours, residents of neighs with a large proportmn of poorly educated individuals had higher bmis than those living in poster sessions v neighbourhoods with more highly educated individuals (p <. ). residing in a neighbourhood with a high proportion of recent immigrants was associated with lower bmi for men (p<. ), but not women. neighbourhood dwelling density, a proxy for walkability, was not associated with bm! for either sex. metropolitan sprawl was associated with higher male bmi (p=. ) but the effect was negligible for women (p=. ). bmi was significantly lower for women (p<. ) living in a city in the province of quebec, even after accounting for the influence of individual and neighbourhood covariates. conclusions: bm! was strongly patterned by individual-level social position in urban canada. the incremental influence on bmi of neighbourhood related to the neighbourhood's social conditions and not to their physical form. metropolitan sprawl was associated with higher bm! for men, a group with longer car-dependent commutes than women. the findings suggest that both individuals and their environments (both social and physical) influence the distribution of bmi in urban populations. introduction: urban environments have been linked to a range of human health issues. in singapore, prevalence of end stage renal disease (esrd) is predicted to rise ( in to in , kidney international, vol. , . the clinical and economic burden of esrd has promoted development of strategies aimed at preventing the development and progression of chronic kidney disease. these include population based screening programs such as the national kidney foundation, sin-gapore\'s (nkfs) "partnership for prevention."the program, aims to reduce incidence of esrd through comprehensive intervention and screening for early detection of urinary abnormalities, blood pressure (bp), and random blood glucose (rbg). objective of this study is to examine gender, race and age wise prevalence of elevated bp, rbg and proteinuria. methodology: this current analysis includes , subjects, age to years, who underwent screening during september and december . participants were asked to give demographic information and the history of diseases. tests were given to get clinical information such as proteinuria, blood glucose, sbp, and dbp. blood pressure abnormalities were defined according to ]nc vi criteria. proteinuria was defined as the presence of plus or greater protein (equivalent to> mg/di) on dipstick analysis. results: there were , ( . %) males. racial distribution was chinese ( . % ), malay ( . % ), indians ( . %) and others ( . % ).among participants, who were apparently "healthy" (asymptomatic and without history of dm, ht, or kd), gender and race wise % prevalence of elevated (bp> / ), rbg (> mg/di) and positive urine dipstick for protein was as follows male: ( . ; . ; . ) female:( . ; . ; . ) chinese:( . ; . ; ) malay: ( . ; . ; . ) indian:( . ; . ; . ) others: ( . ; . ; . ) total:(l . , . , . ). percentage of participants with more than one abnormality were as follows. those with bp> / mmhg, % also had rbg> mg/dl and . % had proteinuria> i. those with rbg> mgldl, % also had proteinuria> and % had bp> / mmhg. those with proteinuria> , % also had rbg> mg/dl, and % had bp> / mmhg. conclusion: we conclude that sub clinical abnormalities in urinalysis, bp and rbg readings are prevalent across all genders and racial groups in the adult population. the overlap of abnormalities, point towards the high risk for esrd as well as cardiovascular disease. this indicates the urgent need for population based programs aimed at creating awareness, and initiatives to control and retard progression of disease. introduction: various theories have been proposed that link differential psychological vulnerability to health outcomes, including developmental theories about attachment, separation, and the formation of psychopathology. research in the area of psychosomatic medicine suggests an association between attachment style and physical illness, with stress as a mediator. there are two main hypotheses explored in the present study: ( t) that individuals living with hiv who were upsychologically vulne~able" at study entry would be more likely to experience symptoms of depression, anxiety and phys ca! illness over. the course of the -month study period; and ( ) life stressors and social support would mediate the relat nship between psychological vulnerability and the psychological ~nd physical outcomes. . (rsles), state-trait anxiety inventory (stai), beck depr~ssi~n lnvento~ (bdi), and~ _ -item pbys~i symptoms inventory. we characterized participants as havmg psychological vulnerability and low resilience" as scoring above on the raas (insecure attachment) or above on the das (negative expectations about oneself). . . . . . " . . ,, . results: at baseline, % of parnc pants were classified as havmg low resilience. focusmg on anxiety, the average cumulative stai score of the low-resilience group was significandy hi~e~ than that of the high-resilience group ( . sd= . versus . sd= . ; f(l, )= . , p <. ). similar results were obtained for bdi and physical symptoms (f( , )= . , p<. and f( , )= . , p<. , respec· tively). after controlling for resilience, the effects of variance in life stres".°rs averaged over time wa~ a_sig· nificant predictor of depressive and physical symptoms, but not of anxiety. ho~e_ver, these assooan~s became non-significant when four participants with high values were removed. s id larly, after controlling for resilience, the effects of variance in social support averaged over time became insignificant. conclusion: not only did "low resilience" predict poor psychological and physical outcomes, it was also predictive of life events and social support; that is, individuals who were low in resilience were more likely to experience more life events and poorer social support than individuals who were resilient. for individuals with vulnerability to physical, psychological, and social outcomes, there is need to develop and test interventions to improve health outcomes in this group. rajat kapoor, ruby gupta, and jugal kishore introduction: young people in india represent almost one-fourth of the total population. they face significant risks related to sexual and reproductive health. many lack the information and skills neces· sary to make informed sexual and reproductive health choices. objective: to study the level of awareness about contraceptives among youth residing in urban and rural areas of delhi. method: a sample of youths was selected from barwala (rural; n= ) and balmiki basti (urban slums; n= ) the field practice areas of the department of community medicine, maulana azad medical college, in delhi. a pre-tested questionnaire was used to collect the information. when/(calen· dar time), by , fisher exact and t were appliedxwhom (authors?). statistical tests such as as appropriate. result: nearly out of ( . %) youth had heard of at least one type of contraceptive and majority ( . %) had heard about condoms. however, awareness regarding usage of contraceptives was as low as . % for terminal methods to . % for condom. condom was the best technique before and after marriage and also after childbirth. the difference in rural and urban groups was statistically signif· icant (p=. , give confidence interval too, if you provide the exact p value). youth knew that contra· ceptives were easily available ( %), mainly at dispensary ( . %) and chemist shops ( . %). only . % knew about emergency contraception. only advantage of contraceptives cited was population con· trol ( . %); however, . % believed that they could also control hiv transmission. awareness of side effects was poor among both the groups but the differences were statistically significant for pills (p= . ). media was the main source of information ( %). majority of youth was willing to discuss a~ut contraceptive with their spouse ( . %), but not with others. . % youth believed that people in their age group use contraceptives. % of youth accepted that they had used contraceptives at least once. % felt children in family is appropriate, but only . % believed in year spacing. . conclusion: awareness about contraceptives is vital for youth to protect their sexual and reproduc· tive health .. knowledge about terminal methods, emergency contraception, and side effects of various contraceptives need to be strengthened in mass media and contraceptive awareness campaigns. mdbot:ls: elderly aged + were interviewed in poor communities in beirut the capital of f:ebanon, ~e of which is a palestinia~. refugee camp. depression was assessed using the i -item geriat· nc depressi~n score (~l?s- ). specific q~estions relating to the aspects of religiosity were asked as well as questions perta rung to demographic, psychosocial and health-related variables. results: depression was prevalent in % of the interviewed elderly with the highest proportion being in the palestinian refugee camp ( %). mosque attendance significantly reduced the odds of being depressed only for the palestinian respondents. depression was further associated, in particular communities, with low satisfaction with income, functional disability, and illness during last year. condiuion: religious practice, which was only related to depression among the refugee population, is discussed as more of an indicator of social cohesion, solidarity than an aspect of religiosity. furthermore, it has been suggested that minority groups rely on religious stratagems to cope with their pain more than other groups. implications of findings are discussed with particular relevance to the populations studied. nearly thirty percent of india's population lives in urban areas. the outcome of urbanization has resulted in rapid growth of urban slums. in a mega-city chennai, the slum populations ( . percent) face greater health hazards due to overcrowding, poor sanitation, lack of access to safe drinking water and environmental pollution. amongst the slum population the health of women and children are most neglected, resulting in burden of both communicable and non-communicable diseases. the focus of the paper is to present the epidemiology profile of children (below years) in slums of chennai, their health status, hygiene and nutritional factors, the social response to health, the trends in child health and urbanization over a decade, the health accessibility factors, the role of gender in health care and assessment impact of health education to children. the available data prove that child health in slums is worse than rural areas. though the slum population is decreasing there is a need to explore the program intervention and carry out surveys for collecting data on some specific health implications of the slum children. objective: during the summer of there was a heat wave in central europe, producing an excess number of deaths in many countries including spain. the city of barcelona was one of the places in spain where temperatures often surpassed the excess heat threshold related with an increase in mortality. the objective of the study was to determine whether the excess of mortality which occurred in barcelona was dependent on age, gender or educational level, important but often neglected dimensions of heat wave-related studies. methods: barcelona, the second largest city in spain ( , , inhabitants in ) , is located on the north eastern coast. we included all deaths of residents of barcelona older than years that occurred in the city during the months of june, july and august of and also during the same months during the preceding years. all the analyses were performed for each sex separately. the daily number of deaths in the year was compared with the mean daily number of deaths for the period - for each educational level. poisson regression models were fitted to obtain the rr of death in with respect to the period - for each educational level and age group. results: the excess of mortality during that summer was more important for women than for men and among older ages. although the increase was observed in all educational groups, in some age-groups the increase was larger for people with less than primary education. for example, for women in the group aged - , the rr of dying for compared to - for women with no education was . ( %ci: . - - ) and for women with primary education or higher was . ( %ci: . - . ). when we consider the number of excess deaths, for total mortality (>= years) the excess numbers were higher for those with no education ( . for women and . for men) and those with less than primary education ( . for women and - for men) than those with more than primary edm:ation ( . for women and - . for men). conclusion: age, gender and educational level were important in the barcelona heat wave. it is necessary to implement response plans to reduce heat morbidity and mortality. policies should he addressed to all population but also focusing particularly to the oldest population of low educational level. introduction: recently there has been much public discourse on homelessness and its imp~ct on health. measures have intensified to get people off the street into permanent housing. for maximum v poster sessions success it is important to first determine the needs of those to be housed. their views on housing and support requirements have to be considered, as th~y ar~ the ones affected. as few res.earch studies mclude the perspectives of homeless people themselves, httle is known on ho~ they e~penence the mpacrs on their health and what kinds of supports they believe they need to obtain housing and stay housed. the purpose of this study was to add the perspectives of homeless people to the discourse, based in the assumption that they are the experts on their own situations and needs. housing is seen as a major deter· minant of health. the research questions were: what are the effects of homelessness on health? what kind of supports are needed for homeless people to get off the street? both questions sought the views of homeless individuals on these issues. methods: this study is qualitative, descriptive, exploratory. semi-structured interviews were conducted with homeless persons on street corners, in parks and drop-ins. subsequently a thematic analysis was carried out on the data. results: the findings show that individuals' experiences of homelessness deeply affect their health. apart from physical impacts all talked about how their emotional health and self-esteem are affected. the system itself, rather than being useful, was often perceived as disabling and dehumanizing, resulting in hopelessness and resignation to life on the street. neither welfare nor minimum wage jobs are sufficient to live and pay rent. educational upgrading and job training, rather than enforced idleness, are desired by most initially. in general, the longer persons were homeless, the more they fell into patterned cycles of shelter /street life, temporary employment /unemployment, sometimes addictions and often unsuccessful housing episodes. conclusions: participants believe that resources should be put into training and education for acquisition of job skills and confidence to avoid homelessness or minimize its duration. to afford housing low-income people and welfare recipients need subsidies. early interventions, 'housing first', more humane and efficient processes for negotiating the welfare system, respectful treatment by service providers and some extra financial support in crisis initially, were suggested as helpful for avoiding homelessness altogether or helping most homeless people to leave the street. this study is a national homelessness initiative funded analysis examining the experiences and perceptions of street youth vis-a-vis their health/wellness status. through in-depth interviews with street youth in halifax, montreal, toronto, calgary, ottawa and vancouver, this paper explores healthy and not-so healthy practices of young people living on the street. qualitative interviews with health/ social service providers complement the analysis. more specifically, the investigation uncovers how street youth understand health and wellness; how they define good and bad health; and their experiences in accessing diverse health services. findings suggest that living on the street impacts physical, emotional and spiritual well·being, leading to cycles of despair, anger and helplessness. the majority of street youth services act as "brokers" for young people who desire health care services yet refuse to approach formal heal~h care organizational structures. as such, this study also provides case examples of promising youth services across canada who are emerging as critical spaces for street youth to heal from the ravages of ~treet cultur~. as young people increasingly make up a substantial proportion of the homeless population in canada, it becomes urgent to explore the multiple ways in which we can support them to regain a sense of wellbeing and "citizenship." p - (c) health and livelihood implications of marginalization of slum dwellers in provision of water and sanitation services in nairobi city elizabeth kimani, eliya zulu, and chi-chi undie . ~ntrodfldion: un-habitat estimates that % of urban residents in kenya live in slums; yet due to their illegal status, they are not provided with basic services such as water sanitation and health care. ~nseque~tly, the services are provided by vendors who typically provide' poor services at exorbitant prices .. this paper investigates how the inequality in provision of basic services affects health and livelihood circumstances of the poor residents of nairobi slums . . methods: this study uses qualitative and quantitative data collected through the ongoing longitudmal .health and demographic study conducted by the african population and health research center m slum communities in n ·rob" w d · · · · ai . e use escnpnve analytical and qualitative techmques to assess h~w concerns relating to water supply and environmental sanitation services rank among the c~mmumty's general and health needs/concerns, and how this context affect their health and livelihood circumstances. results: water ( %) and sanitation ( %) were the most commonly reported health needs and also key among general needs (after unemployment) among slum dwellers. water and sanitation services are mainly provided by exploitative vendors who operate without any regulatory mechanism and charge exorbitantly for their poor services. for instance slum residents pay about times more for water than non-slum households. water supply is irregular and residents often go for a week without water; prices are hiked and hygiene is compromised during such shortages. most houses do not have toilets and residents have to use commercial toilets or adopt unorthodox means such as disposing of their excreta in the nearby bushes or plastic bags that they throw in the open. as a direct result of the poor environmental conditions and inaccessible health services, slum residents are not only sicker, they are also less likely to utilise health services and consequently, more likely to die than non-slum residents. for instance, the prevalence of diarrhoea among children in the slums was % compared to % in nairobi as a whole and % in rural areas, while under-five mortality rates were / , / and / respectively. the results demonstrate the need for change in governments' policies that deprive the rapidly expanding urban poor population of basic services and regulatory mechanisms that would protect them from exploitation. the poor environmental sanitation and lack of basic services compound slum residents' poverty since they pay much more for the relatively poor services than their non-slum counterparts, and also increase their vulnerability to infectious diseases and mortality. since iepas've been working in harm reduction becoming the pioneer in latin america that brought this methodology for brazil. nowadays the main goal is to expand this strategy in the region and strive to change the drug policy in brazil. in this way harm reduction: health and citizenship program work in two areas to promote the citizenship of !du and for people living with hiv/aids offering law assistance for this population and outreach work for needle exchange to reduce damages and dissemination of hiv/aids/hepatit is. the methodology used in outreach work is peer education, needle exchange, condoms and folders distribution to reduce damages and the dissemination of diseases like hiv/aids/hepatitis besides counseling to search for basic health and rights are activities in this program. law attendance for the target population at iepas headquarters every week in order to provide law assistance that includes only supply people with correct law information or file a lawsuit. presentations in harm reduction and drug policy to expand these subjects for police chiefs and governmental in the last year attended !du and nidu reached and . needles and syringes exchanged. in law assistance ( people living with aids, drug users, inject drug users, were not in profile) people attended. lawsuits filed lawsuits in current activity. broadcasting of the harm reduction strategies by the press helps to move the public opinion, gather supporters and diminish controversies regarding such actions. a majority number of police officer doesn't know the existence of this policy. it's still polemic discuss this subject in this part of population. women remain one of the most under seviced segments of the nigerian populationand a focus on their health and other needs is of special importance.the singular focus of the nigerian family welfare program is mostly on demographic targets by seeking to increase contraceptive prevalence.this has meant the neglect of many areas of of women's reproductive health. reproductive health is affected by a variety of socio-cultural and biological factors on on e hand and the quality of the service delivery system and its responsiveness on the other.a woman's based approach is one which responds to the needs of the adult woman and adolescent girls in a culturally sensitive manner.women's unequal access to resources including health care is well known in nigeria in which stark gender disparities are a reality .maternal health activities are unbalanced,focusi ng on immunisation and provision of iron and folic acid,rather than on sustained care of women or on the detection and referral of high risk cases. a cross-sectional study of a municipal government -owned hospitalfrom each of the geo-political regions in igeria was carried out (atotal of ce~ters) .. as _part ~f t~e re.search, the h~spital records were uesd as a background in addition to a -week mtens ve mvesuganon m the obstemc and gynecology departments. . . . : little is known for example of the extent of gynecological morbtdtty among women; the little known suggest that teh majority suffer from one or more reproductive tr~ct infect~ons. although abortion is widespread, it continues to be performed under ilegal and unsafe condmons. with the growing v poster sessions hiv pandemic, while high riskgroups such ascomn;iercial sex workers and their clients have been studied, little has been accomplished in the large populat ns, and particularly among women, regardmgstd an hiv education. . . conclusions: programs of various governmentalor non-governmental agen,c es to mvolve strategies to broaden the narrow focus of services, and more importan~, to put wo~en s reproducnve health services and information needs in the forefront are urgently required. there is a n~d to reonent commuication and education activities to incorprate a wider interpretation of reproducnve health, to focus on the varying information needs of women, men, and youth and to the media most suitable to convey information to these diverse groups on reproductive health. introduction: it is estimated that there are - youths living on the streets, on their own with the assistance of social services or in poverty with a parent in ottawa. this population is under-serviced in many areas including health care. many of these adolescents are uncomfortable or unable to access the health care system through conventional methods and have been treated in walk-in clinics and emergency rooms without ongoing follow up. in march , the ontario government provided the ct lamont institute with a grant to open an interdisciplinary and teaching medical/dental clinic for street youth in a drop-in center in downtown ottawa. bringing community organizations together to provide primary medical care and dental hygiene to the streetyouths of ottawa ages - , it is staffed by a family physician, family medicine residents, a nurse practitioner, public health nurses, a dental hygienist, dental hygiene students and a chiropodist who link to social services already provided at the centre including housing, life skills programs and counselling. project objectives: . to improve the health of high risk youth by providing accessible, coordinated, comprehensive health and dental care to vulnerable adolescents. . to model and teach interdisciplinary adolescent care to undergraduate medical students, family medicine residents and dental hygiene students. methods: non-randomized, mixed method design involving a process and impact evaluation. data collection-qualitative:a) semi-structured interviews b) focus groups with youth quantitative:a) electronic medical records for months b) records (budget, photos, project information). results: in progress-results from first months available in august . early results suggest that locating the clinic in a safe and familiar environment is a key factor in attracting the over youths the clinic has seen to date. other findings include the prevalence of preventative interventions including vaccinations, std testing and prenatal care. the poster presentation will present these and other impacts that the clinic has had on the health of the youth in the first year of the study. conclusions: ) the clinic has improved the health of ottawa streetyouth and will continue beyond the initial pilot project phase. ) this project demonstrates that with strong community partnerships, it is possible meet make healthcare more accessible for urban youth. right to health care campaign by s.j.chander, community health cell, bangalore, india. introduction: the people's health movement in india launched a campaign known as 'right to health care' during the silver jubilee year of the alma ata declaration of 'health for all' by ad in collahoration with the national human rights commission (nhrc). the aim of the campaign was to establish the 'right to health care' as a basic human right and to address structural deficiencies in the pubic health care system and unregulated private sector . . methods: as part of the campaign a public hearing was organized in a slum in bangalore. former chairman of the nhrc chaired the hearing panel, consisting of a senior health official and other eminent people in the city. detailed documentation of individual case studies on 'denial of access to health care' in different parts of the city was carried out using a specific format. the focus was on cases where denial of health services has led to loss of life, physical damage or severe financial losses to the patient. results: _fourte_en people, except one who had accessed a private clinic, presented their testimonies of their experiences m accessing the public health care services in government health centres. all the people, e_xcept_ one person who spontaneously shared her testimony, were identified by the organizations worki_ng with the slum dwellers. corruption and ill treatment were the main issues of concern to the people. five of the fourteen testimonies presented resulted in death due to negligence. the public health cen· n:s not only demand money for the supposedly free services but also ill-treats them with verbal abuse. five of these fourteen case studies were presented before the national human right commission. the poster sessions v nhrc has asked the government health officials to look into the cases that were presented and to rectify the anomalies in the system. as a result of the public hearing held in the slum, the nhrc identified urban health as one of key areas for focus during the national public hearing. cond#sion: a campaign is necessary to check the corrupted public health care system and a covetous private health care system. it helps people to understand the structure and functioning of public health care system and to assert their right to assess heath care. the public hearings or people's tribunals held during the campaign are an instrument in making the public health system accountable. ps- (a) violence among women who inject drugs nadia fairbairn, jo-anne stoltz, evan wood, kathy li, julio montaner, and thomas kerr background/object ives: violence is a major cause of morbidity and mortality among women living in urban settings. though it is widely recognized that violence is endemic to inner-city illicit drug markets, little is known about violence experienced by women injection drug users (!du). therefore, the present analyses were conducted to evaluate the prevalence of, and characteristics associated with, experiencing violence among a cohort of female idu in vancouver. methods: we evaluated factors associated with violence among female participants enrolled in the vancouver injection drug user study (vidus) using univariate analyses. we also examined self-reported relationships with the perpetrator of the attack and the nature of the violent attack. results: of the active iou followed between december , and may , , ( . %) had experienced violence during the last six months. variables positively associated with experiencing violence included: homelessness (or= . , % ci: . - . , p < . ), public injecting (or= . , % ci: . - . , p < . ), frequent crack use (or= . , % ci: . - . , p < . ), recent incarceration (or = . , % cl: . - . , p < . ), receiving help injecting (or = . , % cl: . - . , p < . ), shooting gallery attendance (or = . , % ci: . - . , p < . ), sex trade work (or = . , % cl: . - . , p < . ), frequent heroin injection (or= . , % cl: . - . , p < . ), and residence in the downtown eastside (odds ratio [or] = . , % ci: . - . , p < . ). variables negatively associated with experiencing violence included: being married or common-law (or = . . % ci: . - . , p < . ) and being in methadone treatment (or = . , % ci: . - . , p < . ). the most common perpetrators of the attack were acquaintances ( . %), strangers ( . %), police ( . %), or dealers ( . %). attacks were most frequently in the form of beatings ( . %), robberies ( . %), and assault with a weapon ( . %). conclusion: violence was a common experience among women !du in this cohort. being the victim of violence was associated with various factors, including homelessness and public injecting. these findings indicate the need for targeted prevention and support services, such as supportive housing programs and safer injection facilities, for women iou. introduction: although research on determinants of tobacco use among arab youth has been carried out at several ecologic levels, such research has included conceptual models and has compared the two different types of tobacco that are most commonly used among the lebanese youth, namely cigarette and argileh. this study uses the ecological model to investigate differences between the genders as related to the determinants of both cigarette and argileh use among youth. methodology: quantitative data was collected from youth in economically disadvantaged urban communities in beirut, the capital of lebanon. results: the results indicated that there are differences by gender at a variety of ecological levels of influence on smoking behavior. for cigarettes, gender differences were found in knowledge, peer, family, and community influences. for argileh, gender differences were found at the peer, family, and community l.evels. the differential prevalence of cigarette and argileh smoking between boys and girls s therefore understandable and partially explained by the variation in the interpersonal and community envi.ronment which surrounds them. interventions therefore need to be tailored to the specific needs of boys and girls. introduction: the objective of this study was to assess the relationship between parents' employment status and children' health among professional immigrant families in vancouver. our target communmes v poster sessions included immigrants from five ethnicity groups: south korean, indian, chine~e, ~ussian, and irani~ with professional degrees (i.e., mds, lawyers, engineers, ma?~ger~, and uru~ers ty professors) w h no relevant job to their professions and those who had been hvmg m the studied area at least for months. methodology: the participants were recruited by collaboration from three local community agencies and were interviewed individually during the fall of . ra#lts: totally, complete interviews were analyzed: from south-east asia, from south asia, from russia and other eastern europe. overall, . % were employed, . % were underemployed, % indicated they were unemployed. overall, . % were not satisfied with their current job. russians and other eastern europeans were most likely satisfied with their current job, while south-east asians were most satisfied from their life in canada. about % indicated that their spouses were not satisfied with their life in canada, while % believed that their children are very satisfied from their life in canada. in addition, around % said they were not satisfied from their family relationship in canada. while most of the responders ranked their own and their spouses' health status as either poor or very poor, jut % indicated that their first child's health was very poor. in most cases they ranked their children's health as excellent or very good. the results of this pilot study show that there is a need to create culturally specific child health and behavioral scales when conducting research in immigrant communities. for instance, in many asian cultures, it is customary for a parent either to praise their children profusely, or to condemn them. this cultural practice, called "saving face," can affect research results, as it might have affected the present study. necessary steps, therefore, are needed to revise the current standard health and behavioral scales for further studies by developing a new scale that is more relevant and culturally sensitive to the targeted immigrant families. metboda: database: national health survey (ministry of health www.msc.es). two thousand interviews were performed among madrid population ( . % of the whole); corresponded to older adults ( . % of the . million aged years and over). study sample constitutes . % ( out of ) of those older adults, who live in urban areas. demographic structure (by age and gender) of this population in relation to health services use (medical consultations, dentist visits, emergence services, hospitalisation) was studied using general linear model univariate procedure. a p . ), while age was associated with emergence services use ( % of the population: %, % and % of each age group) and hos~italisation ( % .oft~~ population: %, % and %, of each age ~oup) (p . ) was fou~d with respect to dennst v s ts ( % vs %), medical consultations ( % vs %), and emergence services use ( % vs %), while an association (p= . ) was found according to hospitalisation ( % vs %). age. an~ g~der interaction effect on health services use was not found (p> . ), but a trend towards bosp tal sanon (p= . ) could be considered. concl.uions: demographic structure of urban older adults is associated with two of the four health se~ices use studi~. a relation.ship ber_ween age. and hospital services use (emergence units and hospitalisanon), but not with ~ut-hosp tal sei:vices (medical and dentist consultations), was found. in addition ro age, gender also contnbutes to explam hospitalisation. . sexua experiences. we exammed the prevalence expenences relation to ethnic origin and other sociodemographic variables as wc i as y j die relation between unwanted sexual experiences, depression and agreuion. we did so for boys and prts separately. mdhods: data on unwanted sexual expcric:nces, depressive symptoms (ce.s-d), aggrc:uion (bohi-di and sociodemographic facron were collected by self-report quescionnairc:s administettd to students in the: nd grade (aged - ) of secondary schools in amsterdam, the netherlands. data on the nature ol unwanted sexual experiences were collected during penonal interviews by trained schoolnursn. ltaijtj: overall prevalences of unwanted sexual experiences for boys and girls were . % and . % respectively. unwanted sexual experiences were more often ttported by turkish ( . %), moroc· an ( . %) and surinamese/anrillian boys ( . %) than by dutch boys ( . %). moroccan and turkish girls, however, reported fewer unwanted sexual experiences (respectively . and . %) than durch girls did ( . %). depressive symptoms(or= . , cl= . - . ) covert agression ( r• . , cl• . - . ) and cmrt aggression (or= . , cl• . - . ) were more common in girls with an unwanted sexual experi· met. boys with an unwanted sexual experience reported more depressive symptoms (or= . ; cl• i . .l· . ) and oven agression (or= . , cl= . - . ) . of the reported unwanted sexual experiences rnpec· timy . % and . % were confirmed by male and female adolescents during a personal interview. cond sion: we ..:an conclude that the prevalence of unwanted sexual experiences among turkish and moroccan boys is disturbing. it is possible that unwanted sexual experiences are more reported hy boys who belong to a religion or culture where the virginity of girls is a maner of family honour and talking about sexuality is taboo. more boys than girls did not confirm their initial disdosurc of an lllwalltc:d sexual experience. the low rates of disclosure among boys suggcsu a necd to educ.:atc hcahh care providen and others who work with migrant boys in the recognition and repomng of exu.il ... iction. viramin a aupplc:tmntation i at .h'yo, till far from tafl'eted %. feedinit pracn~:n panku· lerty for new born earn demand lot of educatton ernpha a• cxdu ve hrealt fecdtnit for dnared rcnoj of months was observtd in only .s% of childrrn thoulh colckturm w. givm n rn% of mwly horn ct.ildrm. the proportion of children hclow- waz (malnounshrdl .con" a• h!jh •• . % anj "rt'i· acimy tc.. compared to data. mother's ~alth: from all is womm in ttprod~uvr •ill' poup, % were married and among marned w~ .\ % only w\"rt' u mic wmr cnntr.-:cruve mt h· odl % were married bdorc thc •ar of yean and % had thnr ftnc prcicnancy hcftitt dlt' •icr nf yean. the lt'f'vicn are not uutfactory or they arc adequate but nae unh ed opumally. of thote' l'h mothen who had deliverrd in last one year, % had nailed ntmaral eum nat on ira" oncc, .~o-... bad matt rhan four ttmn and ma ortty had heir tetanus toxotd tnin,"t or"'" nlht "'"'"· ljn r ned rn· win ronductrd . % dchvcnn and % had home deh\'t'oc'i. ~md~: the tervtcn unbud or u led are !tu than dnarame. the wr· l'kft provided are inadequate and on dechm reprcwnttng a looun t ~p of h hnto good coytti\#' ol wr· ncn. l!.ckground chanpng pnoriry cannoc be ruled out u °"" of thc coatnbutory bc f. ps-ii ia) dcpn:wioa aad anuccy ia mip'mu ia awccr._ many de wn, witco tui~bmjer. jack dekker, aart·jan lttkman, wim gonmc:n. and amoud verhoeff ~ a dutch commumry-bucd icudy thawed -moarh•·prc:yalm«i al . ' . kw anx · ay daorden and . % foi' dqrasion m anmttdam. nm .. p tficantly hlllhn than dwwhrft .. dw ~thew diffamca m pttyalcnca att probably rdarcd to tlk' largr populanoa of napaan ..\mturdam. <turkish %, moroccan %, and surinam % . lndttd. ic'wt'll ltudla hatt ~ ~ high prevalena rata among migrant poupi in rbe ncdwrlands. howc'ytt au ttlluchn iuffenod from wry low raporne rara, or med screnung talel thac lack a ~y yabdarcd ~ in order to study the prevalence of depression and anxiety, and the (barriers to) use of mental health care among the different ethnic groups the following study was recently conducted: . the study consisted of a two-step approach. the first step was mcl~ded m the ~ h ith survey of (ahs), and consisted of three screening scales for depression and aruaety (klo, g::q- and mhl- ). in this survey all respondents were asked_ permission for~ second app~ :' t consisted of a structured interview containing the cidi for aruaety and depression, and questtollllalres on health care seeking, amongst others. all respondents who gave permission for a second approachwere invited by jetter for a suuctured interview with multilingual interviewers at home at a preset date and time in the following week. . in total, dutch, turkish, moroccan and surinam respondents took part in the ahs and gave permission for a second approach. in the second step, fo~ ~ tur~h, m~roc can surinamese and dutch respondents, information from the extensive interview was available (res~nse rates between and % ). since the data collection was completed only recently (june ), prevalence estimates can be presented at the conference for the first time. we have shown that with this approach it is feasible to achieve an acceptable response rate in a study on mental health among migrants. therefore we expect that this study will provide reli· able estimates of depression and anxiety in the turkish, moroccan and surinam migrants in amstw! ~· for the first time. in addition, insight into mechanisms underlying the differences between and within ethnic groups and into barriers to mental health care will provide pretexts for the improvement of pre· vention and mental health care for migrant groups. this study aimed to determine spatial patterns of mortality and morbidity of five major health problems in an urban environment: homicides, pregnancy among adolescents ((< years old), asthma hospitalization among young children(< years old) and two mosquito-borne diseasesdengue and visceral leishmaniasis, during - . all events were obtained through the city health database and, subsequently, geoproccsscd using the address of residence and the geographical and administrative division of the municipality, composed by unit of planning (up), which in tum were formed, each one, by census tract units. two research questions were investigated: are there spatial patterns to the events dis· tribution, and moreover, are these patterns overlapping across space? we use thematic maps, index of comparative mortality/morbidity by up and the overlapped rank of the th worse up rates for each event. a spatial pattern of high rates of homicides, proportion of young mothers and hospitalization of asthma were overlapping in areas social and economically disadvantaged. for mosquito-borne diseases, high rates with great dispersion were found in unprivileged areas in contrast with very low rares among privileged ones. these results pointed toward a coexistence of heavier burden of diseases for those living in areas of the city where misery, poverty, lack of political public health may be modulating social health problems. a possible environmental intervention in one mosquito•bome disease might be playing a role in the occurrence of other. although with limitations, this study may provide useful information for a joint urban planning under the public perspective, articulated for use in health impact assessment. jalil safaei bdrod#aion: the association of socioeconomic status (ses), usually measured by income, and health status is an established result in bcalth studies. the poor and low income individuals have lower health sta· tus then_ those with higher incomes. in general. such finding has been usually obtained from sample surveys on speafic populations. a problem with many sample survey$ is that their results are not comparable aaoss ~ndaries as they may use different sampling methods, ask different questions, categorize the answers differently, or define groups differently. moreover, the sample data need to be standardized using the demographic: katurea of a ~ population. this study, however, uses the national population health survey (nphs) cycle public use mictodata files which is based on a common survey template ·~~three~ area in canada, namely montreal, toronto, and vancouver. it also utili .es the built-m stanclatdizaaon of the nphs data which accounts for its complex survey design. . ~:the stu~ usc:s two well-known measures of health inequalitythe relative index of meqaality and die concentranon indexto capture the extent of income related health inequality among poster sessions v urban female and male populations in each of the three metropolitan areas. personal income is classified into ten groups by the nphs with "no income" as the first group and "more than $ , " as the last. health status is measured by three variables -having a chronic condition (chc), self assessed health (sah), and health utility index (hui) -using appropriate indices. alternative formulations are used to calculate the standard deviations of the estimated or calculated measures. the findings of the study suggest that the measured health inequality depends on the health measure used. for chc and hui the measured inequality indices do indicate poorer health for lower income individulas, however, they are not statistically insignificant. health inequalities are more pronounced when health is measured by sah. the results do not support any systematic ranking of the three metropolitan areas in terms of health inequalities. they do not reveal any systematic pattern of inequality between men and women, either. conclusions: despite the use of highly aggregated nphs data, income related health disparities are observed in the three metropolitan areas in canada. this is more the case with self perceived (sah) health. such disparities are preventable and call for broader health policies that address poverty and low income among other social determinants of health. introduction: the analysis of health indicators under the spatial perspective is configured as an important instrument in the detection of intra-urban differentials. this study aimed to examine the spatial distribution of the births occurred in belo horizonte, in , analyzing the presence of spatial clusters of health indicators for newborns (rn) and their mothers, using data from the information system on live birth database (sinasc). method: for each covered area of the basic units of health (ubs), we calculated the proportion of: adolescent mothers, mothers with less than years of schooling, first pregnancy, mothers with four or more pregnancies, dead babies born on previous pregnancies, stillbirths, cesarean section, less than four prenatal care attendance, moderate and severe hypoxemia in the st and th minutes of life, low or very low birth weight. we used empiric bayesian methods for smoothing the estimates. for spatial analysis, the indicators obtained from the global moran (i) index and local indicators of spatial association (lisa) were used. maps were built to allow the visualization of the spatial clusters. in all analysis, significance statistics was considered p~ . . results: a total of , births of residents in belo horizonte were registered in i. the estimated bayesian proportions for the entire municipality was close to the one observed for all variables. analysis using lisa showed the presence of relevant spatial clusters for adolescent and low educated mothers, dead babies form previous pregnancies, cesarean section, low attendance to the prenatal care especially in area with low socio-demographic characteristics. three areas presented consistent clusters, with important spatial auto-correlation for almost all studied indicators. conclusion: the used methodology was configured as a great instrument of detection risk areas where clustering occurs. it can easily be incorporated in any surveillance system as a mechanism for controlling events related to births in the municipality. moreover, it can be applied to discriminate target areas for prompt public health interventions, such as improving health services access and the consolidation of better obstetric practices. introduction: gentrification, the displacement of low income and non-majority people out of longtime neighborhoods and residences is a global phenomenon. it has been identified as occurring in both developed and less developed countries and as inequality persists or increases, many communities are vulnerable to disruption and loss. while there may be some benefits to gentrification, these benefits are less likely to impact those who have been forced to move out of a gentrifying community or those who remain but economically stressed. . . . . this paper lays out a theoretical framework for dent fymg and ~ddressm~. the_ health consequences of gentrification on residents living in a community prior .to o.r durmg gent~ ~ cat. n. by drawing on the literature of housing, sociology, health and urban plannmg, t places genmf catt~n and neighborhood change into the context of other forces affecting th~ .hea.lth of vulnerable populations. it then proposes solutions to prevent or mitigate the impacts of genmf cat on. results: four main categories of consequences potentiallr re~ult from ~entr~fica~~n: !'°°r housing· related issues, spatial effects, mental health impacts and contr bunons to racial ~spanttes m heal~. the housing issues include increased susceptibility to asthma, lead exposure, allergiesl~topy an~. acetdents/ injuries. spatial effects include reduced access to health ~are, reduce~ access to obslttadinonal food sources, decreased physical activity, and increased obesity. the __ pnmary mental health effects_ :ire increased stress increased risk of depression and disruption of trad t onal support networks. in addinon to the above he~lth issues, gentrification has the potential to increase racial disparities in health by reduc· ing access to long term and multi-culturally experienced health care provide~s. conclusions: public health practice provides a framework for addressmg the health consequences of gentrification. in this context primary prevention would involve preventing gentrification in the first place along with a renewed commitment to helping distressed communities a~~ im_proving the quality ~f life for long term residents. the next layer of meeting the challenges of gentrification would be to assjst long rime residents to stay in a community and thus potentially allowing them to participate in the bene~ts of gentrification (such as better public services). only if all these efforts fail -and these other prevennon strategies must be a priority, public policy should then work to help people and instirutions move to other communities through grants and the provision of alternative safe affordable housing and neighborhoods. sarah romans, marsha cohen, and tonia forte lnh'odlletion: there has been sustained interest in urban rural (ur) differences in mental health over the last years of epidemiological research, with most studies reporting higher urban rates of mor· bidity, particularly when psychotic disorders have been studied. most recently, in britain, urban rates of non-psychotic disorder were greater than rural and semi-rural rates, both before and after the more adverse circumstances of urban dwellers were considered (paykel et al ) . surprisingly, there were no ur differences in help seeking. in canada, wang ( ) found greater urban rates for major depression only after he controlled for the confounding effects of race, immigration, employment and marital status, a result reminiscent of work from the us (blazer et ) . rural participants were less likely to have sought help for their mental health problems. in this study, we sought to examine urban/rural differences in rates of depression and help seeking in canada. method; data came from the canadian community health survey . , a community survey conducted by statistics canada of people aged and older, with the total sample size of , respon· dents, % response. analyses used weighted data; differences were assessed by chi-squared. ra.its: bivariate cross-tabulations showed a modest increase in month depression rates for urban ( . %) over rural ( . %, p= . ) dwellers; there were no ur differences when the sample was examined separately by gender and age group ( - , - , - ) . in general, more urban ( . %) than rural people ( . %, p= . ) had sought mental health treatment in the past year. there was no ur difference in helping seeking amongst those with depression (u . %, r . % ns). amongst the whole population, helping seeking was gendered with more urban men accessing help ( . %) than rural men ( . %, p= . ); this did not apply for women ( . % vs . % p= . ). ~ons: the urban-rural demographic continues to generate intriguing findings, even recently when internal migration is common and people can seek out the environment most conducive to their health, ~th physical and mental. people with depression are a disadvantaged, frequently stigmatized group, with ~r quality of life a_nd often impaired function. unlike many other factors associated wi~h urban or rural hfe per se, depression can be treated. the low help seeking rates is a cause for concern, m both the ur~n and_ rural populations. it behooves researchers, policy makers and service planners to ensutt effective services are available for both humane and economic reasons. methods: using united states census income data, we assigned the manhattan community districts to two major socioeconomic groups, manhattan i and ii. manhattan i is composed of community districts with average household incomes above the median for new york city; manhattan ii is those below. with public new york city department of health death records and us census data, we calculated a "standard" new york city population and estimated mortality rate distributions for manhattan i and ii. we then compared these age-adjusted actual mortality distributions with a standard t-test. results: we explored premature deaths using several cut-off points (before the ages of , , and ), and with subcomparisons for males and females. every comparison showed the wealthier area, manhattan i, to have significantly lower premature mortality rates than the lower income manhattan ii. further, we compared age-adjusted mortality rates among the city's five boroughs, and found no significant differences based on local geography alone. conclusions: these findings suggest that in manhattan, characterized by its extremes of wealth and poverty, health status, as measured by premature mortality, does vary significantly with the local income level. in manhattan, the relative average income by community district varies as much as : . this ratio is greater than that found in the other cities we have studied: for example, the range among tokyo's kus is half that in manhattan, or about : . paris has shown the longest life expectancy and changing premature mortality rates. from our preliminary work, we expect to find less variation in premature mortality rates in comparable cities. this study will continue to explore the relationship of premature mortality rates and life expectancy to income levels and different health systems among wcp cities with a view to measuring health policy options. introduction: according to the world health organization (who), smoking-related illness is currently the world's second major cause of death, currently responsible for one out of ten adult deaths worldwide. the who's framework convention on tobacco control (fctc) aims to reduce tobaccorelated disease and deaths by changing national public policies. mexico, which, according to the who, had smoking prevalences of % among adults in and % among health care providers (hcps) in , ratified the fctc in . objective: to examine knowledge of and attitudes towards cigarette smoking and smoking cessation among hcps, and clinical practices regarding smoking cessation. methods: in june , a convenience sample of hcps from one public clinic in urban oaxaca, mexico, part of mexico's national network of public health care clinics, were interviewed in spanish using a verbally administered questionnaire that was standard among all participants. during primary care outpatient visits, hcps were observed treating patients to assess the relative importance of smoking cessation as a health care priority. results: of the hcps interviewed, including ten physicians, three nurses, and five medical students, % reported smoking regularly. all hcps reported assessing patients' history of smoking, knowledge of the health risks associated with smoking, and feeling qualified to discuss these risks with patients. all hcps reported counseling patients who currently smoked to quit. all hcps reported recommending nicotine replacement therapy (eg., patch and/or gum) and/or behavioral therapy (eg., psychologist, support groups) to patients who smoked. all hcps reported that there was no government funding for smoking cessation, and that all costs associated with smoking cessation were patients' out-of-pocket expenses. observation of hcp interaction with patients revealed that hcps always inquired about smoking history with new patients and rarely inquired about smoking history with returning patients. hcps were not observed counseling patients who reported current smoking on smoking cessation methods and its benefits. observation of the clinical environment suggested a focus on preventative child health (eg., immunization, water-borne illnesses), family planning, and chronic diseases (eg., diabetes, hypertension). conclusions: while the mexican government has made smoking cessation a public health priority and hcps report addressing smoking cessation, observation of hcps suggests: ) smoking status is assessed only in new patients; and ) smoking cessation methods are not addresse~. observ_atio~ of hcps and the clinical environment in a public clinic in oaxaca suggests that smoking cessation s of lower priority than other heath care issues. p - (a) urban agriculture and food and nutrition security in kampala, uganda fiona yeudall, renee sebastian, abdelrahman lubowa, selahadin ibrahim, and donald cole introduction: urban agriculture is an important livelihood strategy contributing to household food security by increasing access and availability to food in urban settings (koc et al., ) . the purpose of poster sessions v rhis study was to examine relationships between child nutritional securiry outcomes, household food security, and urban agriculture activiries in kampala, uga~da. . . questionnaires assessing socio-demographic, farmmg and household food secunry (hfsi characreristics were administered to households. food diversiry was ~lculate~ from ~e number of foods consumed over hours for one child ( - years) per household. heigh~ weight,. nud-upper·ann· circumference (muac) and tricep skinfolds (tsf) were measured for the mdex child. z-sc.ores for height-for·age (haz), weighr-for-age (waz) and body mass index (zbmi) were ~~ulated usmg cen· rres for disease control and prevenrion reference data. z-scores for body composition measures were calculated using nhanes i and ii data for african americans. the lms method was used to c~.t for skewed z·score indices. all dara was checked for normaliry and univariable and backward mulnvanablc linear regression analysis conducted. ruwlts: household food securiry was significantly associated with wealth (b= . , p< 'a acre were more dependenr on assets for hfs. although sex of head of household was ~ot related to j-:ifs, it modi· fied relationships in rhar female headed households had greater food securtry when fai:mmg less than , acre compared ro male headed households, and vice versa. hfs was significantly associated with food diversiry (s= . , p). urbanization, especially in developing countries, has substantially increased the vulnerability of rhe mass of low-income urban dwellers. the livelihoods and quality of life for many of the poor espe· cially in larin america, asia, and africa, have deteriorated significantly over the years. urban areas are increasingly unable to provide for their populations, resulting in poverry, massive unemploymenr, job cuts, poor housing, lack of or poor public services, and a compromised health status. botswana, a country rhat lies in the sourhern parr of africa, has had its share of urban problems such as rhe mush· rooming of squarters and low-income urban sertlements. despite efforts to address the substandard living conditions in low-income urban areas, these problems have continued to grow. these living con· diuons are porenrially stressful to rhe residenrs and likely affects their health. the primary aim of the udy wa to examine the complex relationship between communiry-level stressors and interveners and health-related quality of life among residents of low-income neighborhoods in francistown, botswana. u i"" a croa -icctional quantitative design (both descriptive and explanatory) and using primarily cloae-mded interview• with a random sample of residents, this study examined the role of chrome life trnson and environmental quality on overall health status qualiry of life) and the physical, psy· chological and level of independence domains of health. the major hypothesis of the study was that community-levrl stre sor would influence health-related quality of life and that social capital would moderate these relationships. findings indicate that neighborhood quality is a powerful predictor of healrh tatu rhan socioeconomic status and individual life stressors. social capital was also found to he a ificant positive predictor of healrh and also moderator of structural factors. social capital moderated the effects of low environmental quality on level of indrpendence and on physical health outcomn, but nor on psychological and global health outcomes. these findings suggest that as the environment get betttr. stresson are reduced, hence promoting berter health outcomes. the study ends with implication• for social justice, public health and social work practice, and research, focusing mostly on the ~ole of social capital and the environmental quality in predicting health outcomes. spt· cafically • anenhon should be focused on political and civic society's commitment for social justice and poveny alleviation, ~uction of the threat of insecuriry and violence; cultivating social capital and good governance; and improving the health and social environments, especially housing and environ· mental aiutanon to name a few. urban and other uprisings by non-elites that lead to transitions, can disrupt sexual and injection "risk" networks that transmit infectious diseases by changing mixing patterns. they can also weaken urban social networks, their associated protective norms and their informal social control mechanisms which can lead to increased sexual and drug risk behaviors and violence (fullilove ; wallace & wallace , aral , friedman & reid hankins et al ) . for example, the revolution and transition to theocratic rule, and subsequent urban and national conflicts, have been followed by many urban youth in iran engaging in clandestine high-risk sexual and drug behaviors. in palestine, conflicts and restrictions on movement have led to increased fatalities from chronic diseases due to limited access to hospitals and modern medical facilities (union of palestinian medical relief committees); and heroin use and violence-related blood exposure have also increased. social movements "from below" that are rooted both in urban social network dynamics and in underlying patterns of injustice can have both protective and risky effects. for example, the social movements that led to the collapse of the ussr and its dependent governments in other countries-with subsequent increases in sex trade, alcoholism, drug use, tuberculosis, hiv, stis, and mortality in many localities-were based originally on such city-based movements in eastern europe. their impacts on health were mediated by urban social dynamics and structures. some urban social movements have improved health by prevent· ing the spread of hiv, hepatitis and other diseases. examples include movements of (a) gays and lesbians and (b) drug users. these have been rooted in social networks that overlap with risk networks. theories of urban health should include social conflict as a core concept. mechanisms that generate conflicts and the pathways by which conflicts affect health should be a major part of urban health research agendas. p - (c) demographic characteristics of people seen with tuberculosis in lagos state university teaching hospital (lasuth) chest clinic john bako, adewale akeredolu, and wale alabi tuberculosis has become a resurgent public health problem in recent times in the world. because resources are limited, control programmes frequently must target population at greatest risk. the purpose of this study was to study the demographic characteristics of people seen with tuberculosis in lagos state university teaching hospital. a total of patients who have been both radiologically and bacteriologically confirmed tuberculosis patients were used for this study between january and march. ( %) were males, while ( %) were females. notable risk factors among patients with tuberculosis were overcrowding ( . % ), homelessness ( . %) cigarette smoking ( . % ), alcoholism ( . %), non vaccination ( %), secondary contact ( . %) and poor knowledge ( . l 'x,). man· agement history patterns among the patients were herbs ( . 'yo), orthodox medicine ( .h . .l'x.). intervention targeting early-identified groups may be an effective way to reduce the incidence of tuber· culosis. such intervention should focus on health education, modification of life style and improvement of standard of living. p - (c) profiles in urban health in cities of the americas in the countries of the americas, there is an increasing migration of national and international populations to urban centers. this presentation will focus on some of the issues created by this influx of populations, the ways that cities in countries are dealing with them, and the efforts to promote local participation and solutions in management and decision-making. the methodology used to collect this information has been to draw upon and analyze information produced by the mayor's and ministry of health and development offices in each of the cities under consideration. an analysis of the impact of urbanization on health and health determinants will be presented. the information covers issues such as health status by geographic areas within the cities, highlighting issues such as marginality, barriers and physical, economic and cultural constructs and inequities in the delivery of and access to essential services (such as health, education, water, and basic sanitation). issues of governance and citizen participation will be highlighted to provide insight in~o the balance of power and mechanisms for decision-making at the local level. part of the analysis will show the relationship between democratic processes and social participation. public ~olicies will be reviewed to indicate those that are most beneficial in promoting health and overcoming barriers to it, as well as ways of capitalizing on local assets and resources. final~y, evidence of effectiveness of various strategies will be indicated. the presentation will conclude wuh suggesuons for future strategic directions to improve the quality of life and the promotion of health in large urban centers of the americas. introduction: much of the illicit drug in mexico is concentrated in northern border areas. the mile border between the u.s. and mexico is also characterized by migration; the border crossing between tijuana, baja california, mexico and san diego, california, u.s.a. is rep~rt~dl~ the busiest land border crossing in the world. we attempt to describe the migration scene among m ect on drug users (idus) m tijuana and investigate service needs. methods: migration trends were investigated in a cross-sectional study conducted from february to june among idus in tijuana. enrollment criteria included informed consent, being years or older, and having injected drugs within the prior month. subjects were recruited by respondent-dnven sampling and were administered a quantitative survey and serology for hiv, hcv, and syphilis. logistic regression was used to compare idus who had migrated to the u.s. versus those who had not. results: of idus enrolled, % were male and median age and age at first injection were and , respectively. drug combinations injected most frequently in the past months were heroin ( % and crystal methamphetamine mixed with heroin ( %). of those enrolled, responded to quesnons on migration and drug treatment and were included in this analysis. although % had resided in tijuana for at least years, % of users were born outside of baja california. working outside of mexico was common, with % working abroad in the last years ( % in u.s.), and % in the past year. in the last months, % of idus had crossed the border to the u.s., with % crossing at least once per month. those working outside of mexico in the past year were less likely to have ever received substance abuse treatment, [ % vs. %, or . , ] and were marginally less likely to have received drug treatment in the past months [ % vs. %, or . , % ci ( . - . )]. drug use patterns, age and gender did not differ between migrants and non-migrants, although migrants were more likely to report being in need of substance abuse treatment ( % vs. %, respectively). conclusions: migration is common among idus in tijuana. maintaining drug treatment regimens and determining how to best target education and services to a highly mobile population pose challenges to officials on both sides of the border. these data underscore the need to develop coordinated binational prevention and treatment efforts. introduction: despite the expanding literature on the important role public policy plays in influencing the broader determinants of the public\'s health, profound differences exist among jurisdictions in rhe attention placed upon such activities. we take an international perspective on health by examining rhe d?minant public _health paradigms of canada, usa, uk, and sweden and exploring how these paradigms shape public health practice. _method: we carefully analyze governmental and public health agencies documents to discern ~he dommant para~igms driving public health approaches and practices. we also consider the unique paht · cal and economic contexts within each nation and consider how these contexts drive public health pahcy and approaches. . . ~u~: the canadian and usa public health communities -with some exceptions --focus upon m~ividuahzed approaches to risk management. in contrast, the uk and swedish public health scenes are oriented toward broader approaches to health determinants. we find that the extent to which govern· ments, public health agencies and public health workers concern themselves with public policy approaches £<_> ~ddress ~ro.ad~r .determinants of health depends upon the particular health parad'.~ adhered. ~o withm each urisd ctton. and whether a paradigm is adopted depends upon the ideologi~a and pol~ncal context of each nation. nations such as sweden that have a long tradition of public policies promonng social jus~ce an~ equity are naturally receptive to evolving population health concepts. '[he usa represen~ a ~bey en~ro~~t where such is~ues are clear!~ subordinate. ., our findings mdicate that there s a strong political component that influences pubh ~ealth a~proaches and practi~ within the jurisdictions examined. the implications are that those seek· m~ to raise the broader detennmants of the public's health should work in coalition to raise these issues with non-health organizations and age · ca d d th · - badrgrollnd: in developed countries, social inequalities in health have endured or even worsened comparatively throughout different social groups since the s. in france, a country where access to medical and surgical care is theoretically affordable for everyone, health inequalities are among the high· est in western europe. in developing countries, health and access to care have remained critical issues. in madagascar, poverty has even increased in recent years, since the country wenr through political crisis and structural adjustment policies. objectives. we aimed to estimate and compare the impact of socio· economic status but also psychosocial characteristics (social integration, health beliefs, expectations and representation, and psychological characteristics) on the risk of having forgone healthcare in these dif· fercnt contexts. methods: population surveys conducted among random samples of households in some under· served paris neighbourhoods (n= ) and in the whole antananarivo city (n= ) in , using a common individual questionnaire in french and malagasy. reslllts: as expected, the impact of socioeconomic status is stronger in antananarivo than in paris. but, after making adjustments for numerous individual socio-economic and health characteristics, we observed in both cities a higher (and statically significant) occurrence of reponed forgone healthcare among people who have experienced childhood and/or adulthood difficulties (with relative risks up to and .s respectively in paris and antananarivo) and who complained about unhealthy living conditions. in paris, it is also correlated with a lack of trust in health services. coneluions: aside from purely financial hurdles, other individual factors play a role in the non-use of healthcare services. health insurance or free healthcare seems to be necessary hut not sufficienr to achieve an equitable access to care. therefore, health policies must not only focus on the reduction of the financial barriers to healthcare, but also must be supplemented by programmes (e.g. outreach care ser· vices, health education, health promotion programmes) and discretionary local policies tailored to the needs of those with poor health concern .. acknowledgments. this project was supported by the mal>io project and the national institute of statistics (instat) in madagascar, and hy the development research institute (ird) and the avenir programme of the national institute of health and medical research (inserm) in france. for the cities of developing countries, poverty is often described in terms of the living standard~ of slum populations, and there is good reason to believe that the health risks facing these populations are even greater, in some instances, than those facing rural villagers. yet much remains to be learned ahour the connections between urban poverty and health. it is not known what percentage of all urban poor live in slums, that is, in communities of concentrated poverty; neither is it known what proportion of slum residents are, in fact, poor. funhermore, no quantitative accounting is yet available that would sep· arare the health risks of slum life into those due to a househoid•s own poverty and those stemminic from poveny in the surrounding neighborhood. if urban health interventions are to be effectively targeted in developing countries, substantial progress must be made in addressing these cenrral issues. this paper examines poverty and children's health and survival using two large surveys, one a demographic and health survey fielded in urban egypt (with an oversampling of slums) and the other a survey of the slums of allahabad, india. using multivariate statistical methods. we find, in both settings: ( substan· rial evidence of living standards heterogeneity within the slums; ( strong evidence indicating that household-level poverty is an imponant influence on health; and ( ) staristically significant (though less strong) evidence that with household living standards held constant, neighborhood levels of poverty adversely affect health. the paper doses with a discussion of the implications of these findings for the targeting of health and poverty program interventions. p - (a) urban environment and the changing epidemiological surfacr. the cardiovascular ~ &om dorin, nigeria the emergence of cardiovascular diseases had been explained through the concomitants o_f the demographic transition wherein the prevalent causes of morbidity and monality ~hangr pr~mmant infectious diseases to diseases of lifestyle or chronic disease (see deck, ) . a ma or frustration m the v poster sessions case of cvd is its multifactural nature. it is acknowledged that the environment, however defined is the d · f · t' b tween agents and hosts such that chronic disease pathogenesis also reqmre a me an o mterac ion e . spatio-temporal coincidence of these two parties. what is not clear is which among ~ever~( potennal fac· · h b pace exacerbate cvd risk more· and to what extent does the ep dem olog cal trans · tors m t e ur an s ' . . . . tion h othesis relevant in the explanation of urban disease outlook even the developmg cities like nigeri~: thesis paper explorer these within a traditional city in nigeria. . . . the data for the study were obtained from two tertiary level hospitals m the metropolis for years ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . the data contain reported cases of cvd in the two facilities for the period. adopting a series of parametric and non-parametric statistics, we draw inferences between the observed cases of cvds and various demographic and locational variables of the patients. findings: about % of rhe cases occurred in years ( ) ( ) ( ) coinciding with the last year of military rule with great instability. . % occurred among male. . % also occurred among people aged - years. these are groups who are also likely to engage in most stressful life patterns. ~e study also shows that % of all cases occurred in the frontier wards with minor city areas also havmg their •fair' share. our result conformed with many empirical observation on the elusive nature of causation of cvd. this multifactoral nature had precluded the production of a map of hypertension that would be consistent with ideas of spatial prediction. cvd -cardiovascular diseases. mumbai is the commercial capital of india. as the hub of a rapidly transiting economy, mumbai provides an interesting case study into the health of urban populations in a developing country. with high-rise multimillion-dollar construction projects and crowded slums next to each other, mumbai presents a con· trast in development. there are a host of hi-tech hospitals which provide high quality care to the many who can afford it (including many westerners eager to jump the queue in their healthcare systems-'medical tour· ism'), at the same time there is a overcrowded and strained public healthcare system for those who cannot afford to pay. voluntary organizations are engaged in service provision as well as advocacy. the paper will outline role of the voluntary sector in the context of the development of the healthcare system in mumbai. mumbai has distinct upper, middle and lower economic classes, and the health needs and problems of all three have similarities and differences. these will be showcased, and the response of the healthcare system to these will be documented. a rising hiv prevalence rate, among the highest in india, is a challenge to the mumbai public healthcare system. the role of the voluntary sector in service provision, advocacy, and empowerment of local populations with regards to urban health has been paramount. the emergence of the voluntary sector as a major player in the puzzle of urban mumbai health, and it being visualized as voices of civil society or communiry representatives has advantages as well as pitfalls. this paper will be a unique attempt at examining urban health in india as a complex web of players. the influence of everyday socio·polirical-cultural and economic reality of the urban mumbai population will be a cross cutting theme in the analysis. the paper will thus help in filling a critical void in this context. the paper will thus map out issues of social justice, gender, equiry, effect of environment, through the lens of the role of the voluntary sector to construct a quilt of the realiry of healthcare in mumbai. the successes and failures of a long tradi· tion of the active advocacy and participation of the voluntary sector in trying to achieve social justice in the urban mumbai community will be analyzed. this will help in a better understanding of global urban health, and m how the voluntary sector/ngos fir into the larger picture. ba~und: o~er. half _of n~irobi's . million inhabitants live in illegal informal settlements that compose yo of the city s res dent al land area. the majority of slum residents lack access to proper san· iranon and a clean and adequate water supply. this research was designed to gain a clearer understand· mg of what kappr · · · h f . . opnate samtanon means or the urban poor, to determine the linkages between gender, hvehhoods, and access to water and sanitation, and to assess the ability of community sanitation blocks to meet water and sanitation needs in urban areas. m~tbojs_: _a household survey, gender specific focus groups and key informant interviews were conducted m maih saba, a peri-urban informal settlement. qualitative and quantitative research tools were u~ to asses~ the impact and effectiveness of community sanitation blocks in two informal settlements. results ropna e samtarmn me u es not only safe and clean latrines, but also provision ° adequate drainage and access to water supply for cleaning of clothes and homes. safety and cleanliness poster sessions v were priorities for women in latrines. levels of poverty within the informal settlements were identified and access to water and sanitation services improved with increased income. environmental health problems related to inadequate water and sanitation remain a problem for all residents. community sanitation blocks have improved the overall local environment and usage is far greater than envisioned in the design phase. women and children use the blocks less than men. this is a result of financial, social, and safety constraints. the results highlight the importance a need to expand participatory approaches for the design of water and sanitation interventions for the urban poor. plans need to recognize "appropriate sanitation" goes beyond provision of latrines and gender and socioeconomic differences must be taken into account. lessons and resources from pilot projects must be learned from, shared and leveraged so that solutions can be scaled up. underlying all the challenges facing improving water and sanitation for the urban poor are issues of land tenure. p - (c) integrating tqm (total quality management), good governance and social mobilization principles in health promotion leadership training programmes for new urban settings in countries/ areas: the prolead experience susan mercado, faren abdelaziz, and dorjursen bayarsaikhan introduction: globalization and urbanization have resulted in "new urban settings" characterized by a radical process of change with positive and negative effects, increased inequities, greater environmental impacts, expanding metropolitan areas and fast-growing slums and vulnerable populations. the key role of municipal health governance in mitigating and modulating these processes cannot be overemphasized. new and more effective ways of working with a wide variety of stakeholders is an underpinning theme for good governance in new urban settings. in relation to this, organizing and sustaining infrastructure and financing to promote health in cities through better governance is of paramount importance. there is a wealth of information on how health promotion can be enhanced in cities. despite this, appropriate capacity building programmes to enable municipal players to effectively respond to the challenges and impacts on health of globalization, urbanization and increasing inequity in new urban settings are deficient. the who kobe centre, (funded by the kobe group( and in collaboration with regional offices (emro, searo, wpro) with initial support from the japan voluntary contribution, developed a health promotion leadership training programme called "prolead" that focuses on new and autonomous structures and sustainable financing for health promotion in the context of new urban settings. methodology: country and/or city-level teams from areas, (china, fiji, india, japan, lebanon, malaysia, mongolia, oman, philippines, republic of korea, tonga and viet nam) worked on projects to advance health promotion infrastructure and financing in their areas over a month period. tools were provided to integrate principles of total quality management, good governance and social mobili .ation. results: six countries/areas have commenced projects on earmarking of tobacco and alcohol taxes for health, moblization of sports and arts organizations, integration of health promotion and social health insurance, organizational reforms, training in advocacy and lobbying, private sector and corporate mobilization and community mobilization. results from the other six areas will be reported in ..;obcr. conclusions: total quality management, good governance and social mobilization principles and skills are useful and relevant for helping municipal teams focus on strategic interventions to address complex and overwhelming determinants of health at the municipal level. the prolead training programmes hopes to inform other processes for building health promotion leadership capacity for new urban settings. the impact of city living and urbanization on the health of citizens in developing countries has received increasing attention in recent years. urban areas contribute largely to national economies. however, rapid and unplanned urban growth is often associated with poverty, environmental degradation and population demands that outstrip service capacity which conditions place human health at risk. local and national governments as well as multi national organizations are all grappling with the challenges of urbanization. with limited data and information available, urban health characteristics, including the types, quantities, locations and sources in kampala, are largely unknown. moreover, there is n? basis for assessing the impact of the resultant initiatives to improve health ~onditions amo~g ~o": ": um ties settled in unplanned areas. since urban areas are more than the aggregation ?f ~?pie w~th md_ v dual risk factors and health care needs, this paper argues that factors beyond the md v dual, mcludmg the poster sessions v · i d h · i · ment and systems of health and social services are determinants of the health soc a an p ys ca environ . of urban populations. however, as part of an ongoing study? ~s pape~ .addresses the basic concerns of urban health in kampala city. while applying the "urban hvmg conditions and the urban heal~ pen· alty" frameworks, this paper use aggregated urban health d~ta t~ explore the role of place an~ st tu· tions in shaping health and well-being of the population m kampala by understanding how characteristics of the urban environment and specific features of the city are causally related to health of invisible and forgotten urban poor population: results i~dica~e that a .range o~ urb~n he~l~h hazards m the city of kampala include substandard housing, crowdmg, mdoor air poll.ut on, msuff c ent a~d con· taminated water, inadequate sanitation and solid waste management services, vector borne .diseases, industrial waste increased motor vehicle traffic among others. the impact of these on the envtronment and community.health are mutually reinforcing. arising out of the withdra"'.al of city pl~nning systems and service delivery systems or just planning failure, thousands of people part cularl~ low-mc~me groups have been pushed to the most undesirable sections of the city where they are faced with ~ va_r ety ~f envj· ronmental insults. the number of initiatives to improve urban health is, however, growing mvolvjng the interaction of many sectors (health, environment, housing, energy, transportation and urban planning) and stakeholders (local government, non governmental organizations, aid donors and local community groups). key words: urban health governance, health risks, kampala. introduction: the viability of urban communities is dependent upon reliable and affordable mass transit. in particular, subway systems play an especially important role in the mass transit network, since they provide service to vast numbers of ridersseven of the subway systems worldwide report over one billion passenger rides each year. surprisingly, given the large number of people potentially affected, very little is known about the health and safety hazards that could affect both passengers and transit workers; these include physical (e.g., noise, vibration, accidents, electrified sources, temperature extremes), biological (e.g., transmission of infectious diseases, either through person-to-person spread or vector-borne, for example, through rodents), chemical (e.g., exposure to toxic and irritant chemicals and metals, gas emissions, fumes), electro-magnetic radiation, and psychosocial (e.g., violence, workstress). more recently, we need to consider the threat of terrorism, which could take the form of a mass casualty event (e.g., resulting from conventional incendiary devices), radiological attack (e.g., "dirty bomb"), chemical terrorist attack (e.g., sarin gas), or bioterrorist attack (e.g., weapons grade anthrax). given the large number of riders and workers potentially at risk, the public health implications are considerable. methods: to assess the hazards associated with subways, a structured review of the (english) litera· ture was conducted. ruults: based on our review, non-violent crime, followed by accidents, and violent crimes are most prevalent. compared to all other forms of mass transit, subways present greater health and safety risks. however, the rate of subway associated fatalities is much lower than the fatality rate associated with automobile travel ( . vs. . per million passenger miles), and cities with high subway ridership rates have a % lower per capita rate of transportation related fatalities than low ridership cities ( . versus . annual deaths per , residents). available data also suggest that subway noise levels and levels of air pollutants may exceed recommended levels. . ~: there is a paucity of published research examining the health and safety hazards associated with subways. most of the available data came from government agencies, who rely on passively reported data. research is warranted on this topic for a number of reasons, not only to address important knowled~ gaps, but also because the population at potential risk is large. importantly, from an urban perspecnve, the benefits of mass transit are optimized by high ridership ratesand these could be adversely affu:ted by unsafe conditions and health and safety concerns. veena joshi, jeremy lim. and benjamin chua ~ ~rban health issues have moved beyond infectious diseases and now centre largely on chrome diseases. diabetes is one of the most prevalent non-communicable diseases globally. % of adult ¥ benefit in providing splash pads in more parks. given the high temperature and humidity of london summers, this is an important aspect and asset of parks. interviewed parents claimed to visit city parks anywhere between to days per week. corrduion: given that the vast majority of canadian children are insufficiently active to gain health benefits, identifying effective qualities of local parks, that may support and foster physical activity is essential. strategies to promote activity within children's environments are an important health initiative. the results from this study have implications for city planners and policy makers; parents' opinions of, and use of city parks provides feedback as to the state current local parks, and modifications that should be made for new ones being developed. this study may also provide important feedback for health promoters trying to advocate for physical activity among children. introdt clion: a rapidly increasing proportion of urban dwellers in africa live below the poverty line in overcrowded slums characterized by uncollected garbage, unsafe water, and deficient sanitation and overflowing sewers. this growth of urban poverty challenges the commonly held assumption that urban populations enjoy better health than their rural counterparts. the objectives of this study are (i) to compare the vaccination status, and morbidity and mortality outcomes among children in the slums of nairobi with rural kenya, and (ii) to examine the factors associated with poor child health in the slums. we use data from demographic and health survey representative of all slum settlements in nairobi city carried out in by the african population & health research center. a total of , women aged - from , households were interviewed. our sample consists of , children aged - months. the comparison data are from the kenya demographic and health survey. the outcomes of interest include child vaccination status, morbidity (diarrhea, fever and cough) and mortality, all dichotomized. socioeconomic, environmental, demographic, and behavioral factors, as well as child and mother characteristics, are included in the multivariate analyses. multilevel logistic regression models are used. l'nlimin ry rest lts: about % of children in the slums had diarrhea in the two weeks prior to the survey, compared to % of rural children. these disparities between the urban poor anj the rural residents are also observed for fever ( % against %), cough ( % versus %), infant mortality ( / against / ), and complete vaccination ( % against %). preliminary multivariate results indicate that health service utilization and maternal education have the strongest predictive power on child morbidity and mortality in the slums, and that household wealth has only minor, statistically insignificant effects. conclruion: the superiority of health of urban children, compared with their rural counterparts, masks significant disparities within urban areas. compared to rural residents, children of slum dwellers in nairobi are sicker, are less likely to utilize health services when sick, and stand greater risk to die. our results suggest policies and programs contributing to the attainment of the millennium development goal on child health should pay particular attention to the urban poor. the insignificance of socioeconomic status suggests that poor health outcomes in these communities are compounded by poor environmental sanitation and behavioral factors that could partly be improved through female education and behavior change communication. introduction: historic trade city surat with its industrial and political peace has remained a center of attraction for people from all the comers of india resulting in to pop.ulatio~ explosio~ a~d stressed social and service infrastructure. the topography,dimate and demographic profile of the city s threat to the healthy environment. aim of this analysis is to review the impact of managemt'nt reform on health indicators. method: this paper is an analysis of the changing profile of population, sanitary infr~s~rucrure, local self government management and public health service reform, secondary health stat st cs data, health indicator and process monitoring of years. . . health of entire city and challenge to the management system. plague outbr~ak ( ) was the turning point in the history of civic service management including p~blic ~e~lth service management. ~ocal self government management system was revitalized by reg~lar_ field v s ts o~ al~ cadre~, _decentraltzanon of power and responsibility, equity, regular vigilant momtormg, commumcanon facility, ream_approach and people participation. reform in public health service management was throu_gh stan~~rd zed intervention protocol, innovative intervention, public private partnership, community part c panon, academic and service institute collaboration and research. sanitation service coverage have reached nearer to universal. area covered by safe water supply reached to %( ) from % ( ) and underground drainage to % ( ) from % ( ) the overhauling of the system have reflected on health indicators of vector and water born disease. malaria spr declined to . ( ) from . 'yo(! ) and diarrhea case report declined to ( ) from ( ). except dengue fever in no major disease outbreaks are reported after . city is recipient of international/national awards/ranking for these achievements. the health department have developed an evidence and experience based intervention and monitoring system and protocol for routine as well as disaster situation. the health service and management structure of surat city have emerged as an urban health model for the country. introduction: the center for healthy communities (chc) in the department of family and com· munity medicine at the medical college of wisconsin developed a pilot project to: ) assess the know· ledge, attitudes, and behaviors of female milwaukee public housing residents related to breast cancer; develop culturally and literacy appropriate education and screening modules; ) implement the developed modules; ) evaluate the modules; and ) provide follow-up services. using a community-based participatory research model the chc worked collaboratively with on-site nurse case management to meet these objectives. methods: a "breast health kick off event" was held at four separate milwaukee public housing sites for elderly and disabled adults. female residents were invited to complete a -item breast health survey, designed to accommodate various literacy levels. responses were anonymous and voluntary. the survey asked women about their previous physical exams for breast health, and then presented a series of state· ments about breast cancer to determine any existing myths. the final part gathered information about personal risk for breast cancer, the highest level of education completed, and whether the respondents h;td ever used hormone replacement therapy and/or consumed alcohol. responses were collected for descriptive analysis. results: a total of surveys (representing % of the total female population in the four sites) were completed and analyzed. % reported that they had a physical exam in the previous rwo years. % of respondents indicated they never had been diagnosed with breast cancer. % reported having had a mammogram and % having had a clinical breast exam. those that never had a mammogram reported a fear of what the provider would discover or there were not any current breast problems ro warrant an exam. % agreed that finding breast cancer early could lower the chance of dying of cancer. over % reported that mammograms were helpful in finding cancer. however, % believed that hav· ing a mammogram actually prevents breast cancer. % indicated that mammograms actually cause cancer and % reported that a woman should get a mammogram only if there is breast cancer in her family. conclusion: this survey indicates that current information about the importance of mammograms and clinical breast exams is reaching traditionally underserved women. yet there are still critical oppor· tunities to provide valuable education on breast health. this pilot study can serve as a tool for shaping future studies of health education messages for underserved populations. located in a yourh serv· ~ng agency m downtow~ ottawa, the clinic brings together community partners to provide primary medical care. and dent~i hygiene t? the street youths of ottawa aged - . the primary goal of the project is to provide accessible, coordinated, comprehensive health and dental care to vulnerable adolescents. these efforts respond to the pre-existing body of evidence suggesting that the principle barrier in accessing such care for these youths are feelings of intimidation and vulnerability in the face of a complex healthcare system. the bruyere fhn satellite clinic is located in the basement of a downtown drop-in and brings together a family medicine physician and her residents, a dental hygienist and her nd year students, a nurse practitioner, a chiropodist and public health nurses to provide primary care. the clinic has been extremely busy and well received by the youth. this workshop will demonstrate how five community organizations have come together to meet the needs of high risk youths in ottawa. this presentation will showcase the development of the clinic from its inception through its first year including reaction of the youths, partnerships and lessons learned. it will also focus on its sustainability without continued funding. we hope to have developed a model of service delivery that could be reproduced and sustained in other large cities with faculties of medicine. methods: non-randomized, mixed method design involving a process and impact evaluation. data collection-qualitative-a) semi structured interviews with providers & partners b)focus groups with youth quantitative a)electronic medical records for months records (budget, photos, project information). results: ) successfully built and opened a medicaudental clinic which will celebrate its year anniversary in august. ) over youths have been seen, and we have had over visits. conclusion: ) the clinic will continue to operate beyond the month project funding. ) the health of high risk youth in ottawa will continue to improve due to increased access to medical services. p - (a) health services -for the citizens of bangalore -past, present and future savita sathyagala, girish rao, thandavamurthy shetty, and subhash chandra bangalore city, the capital of karnataka with . million is the th most populous city in india; supporting % of the urban population of karnataka, it is considered as one of the fastest growing cities in india. known as the 'silicon valley of india', bangalore is nearly years old. bangalore city corporation (bmp), is a local self government and has the statutory commitment to provide to the citizens of bangalore: good roads, sanitation, street lighting, safe drinking water apart from other social obligations, cultural development and poverty alleviation activities. providing preventive and promotive heahh services is also a specific component. the objective of this study was to review the planning process with respect to health care services in the period since india independence; the specific research questions being what has been the strategies adopted by the city planners to address to the growing needs of the population amidst the background of the different strategies adopted by the country as a whole. three broad rime ranges have been considered for analysis: the s, s and the s. the salient results are: major area of focus has been on the maternal and child care with activities ranging from day-care to in-patient-care; though the number of institutions have grown from to the current day , their distribution has been far from satisfactory; obtaining support from the india population projects and major upgradarions have been undertaken in terms of infrastructure; over the years, in addition to the dispensaries of modern system of medicine, local traditional systems have also been initiated; the city has partnered with the healthy cities campaign with mixed success; disease surveillance, addressing the problems related to the emerging non-communicable diseases including mental health and road traffic injuries are still in its infancy. isolated attempts have been made to address the risks groups of elderly care and adolescent care. what stands out remarkably amongst the cities achievements is its ability to elicit participation from ngos, cbos and neighbourhood groups. however, the harnessing of this ability into the health sector cannot be said totally successful. the moot question in all the above observed development are: has the city rationally addressed it planning needs? the progress made so far can be considered as stuttered. the analysis and its presentation would identify the key posirive elements in the growth of banglore city and spell a framework for the new public health. introduction: anaemia associated with pregnancy is a major public health problem all over the world. different studies in different parts of india shown prevalence of anaemia between - %. anaemia remains a serious health problem in pregnancy despite of strong action taken by the government of india through national programmes. in the present study we identified th~ social beha~iors, responsible for low compliance of if a tablets consumption in pregnancy at community level and intervention was given with new modified behaviors on trial bases. . in vadodara urban. anganwadies out of were selected from the list by random sampling for tips (trials of improved practices) study. . . participants: pregnant women ( , intervention group+ , control. group) registered m the above anganwadies. study was conducted in to three phases: phase: . formative research and baseline survey (frbs). data was collected from all pregnant women to identify behaviors that are responsible for low compliance of ifa tablets. both qualitative and quantitative data were collected. haemoglobin was estimated of all pregnant women by haemo-cue. phase: . phase of tips. behaviors were identified both social & clinical for low compliance of ifa tablets consumption in pregnancy from frbs and against those, modified behaviors were proposed to pregnant women in the intervention group on trial bases by health education. trial period of weeks was given for trial of new behaviors to pregnant women in the interven· tion group. phase: . in this phase, feedbacks on behaviors tried or not tried were taken from pregnant women in intervention group. haemoglobin estimation was carried out again in all pregnant women. at the end of the study, messages were formulated on the bases of feedbacks from the pregnant women. results: all pregnant women in the intervention group had given positive feedback on new modified behaviors after intervention. mean haemoglobin concentration was higher in intervention group ( . ± . gm%) than control group ( . ± . gm%). ifa tablets compliance was improved in intervention group ( . %) than control group ( . %). conclusion: all pregnant women got benefits after trial of new modified behaviors in the intervention group. messages were formulated from the new modified behaviors, which can be used for longterm strategies for anaemia control in the community. introduction: in order to develop a comprehensive mch handbook for pregnant women and to assess its effect among them, a pilot study was carried out at the maternal and child health training institute (mchti), in dhaka, bangladesh. methods: from mchti a sample of pregnant women was selected and all subjects were women who were attending the first visit of their current pregnancy by using a random sampling method. of the subjects, women were given the mch handbook as case and women were not given the handbook as control. data on pre and post intervention of the handbook from the cases and controls were taken from data recording forms between the st of november and st of october, and data was analysed by using a multilevel analysis approach. this was a hospital-based action (case-control) research, and was applied in order to measure the outcome of pre and post intervention following the introduction of the handbook. data was used to assess the effects of utilisation of the handbook on women's knowledge, practice and utilisation of mch services. results: this study showed that the change of knowledge about antenatal care visits was . % among case mothers. knowledge of danger signs improved . %, breast feeding results . %, vaccination . % and family planning results improved . % among case. results showed some positive changes in women's attitudes among case mothers and study showed the change of practice in antenatal care visits was .u. % in the case. other notable changes were: change of practice in case mother's tetanus toxoid (ti), . %; and family planning . %. in addition, handbook assessment study indicated that most women brought the handbook on subsequent visits ( . %), the handbook was highly utilised (i.e. it was read by . %, filled-in by . %, and was used as a health education tool by . %). most women kept the handbook ( . %) and found it highly useful ( . %) with a high client satisfaction rate of . %. conclusion: pregnant women in the case group had higher knowledge, better practices, and higher utilisation of mch services than mothers in the control groups who used alternative health cards. if the handbook is developed with a focus on utilising a problem-oriented approach and involving the recomendations .of end~users, it is anticipated that the mch handbook will contribute significantly to ensuring the quahry of hfe of women and their children in bangladesh. after several meetmgs to identify the needs of the community, a faso clinic was opened at ncfs. health care professionals from smh joined with developmental and social service workers from ncfs to implement the faso diagnostic process and to provide culturally appropriate after-care. the clinic is unique in that its focus is the high risk urban aboriginal population of toronto. it accepts referrals of not only children and youth, but also of adults. lessons learned: response to the faso clinic at native child and family services has been overwhelming. aboriginal children with f asd are receiving timely diagnosis and interventions. aboriginal youth and adults who have been struggling with poveny, substance abuse, and homelessness are more willing to enter the ncfs centre for diagnosis and treatment. aboriginal infants prenatally exposed to alcohol born at st. michael's hospital or referred by other centres have access to the developmental programs located in both of the partnering agencies. the presentation will describe the clinic's development, and will detail the outcomes described, including interventions unique to the aboriginal culture. p - (c) seeds, soil, and stories: an exploration of community gardening in southeast toronto carolin taran, sarah wakefield, jennifer reynolds, and fiona yeudall introduction: community gardens are increasingly seen as a mechanism for improving nutrition and increasing food security in urban neighbourhoods, but the evidence available to support these claims is limited. in order to begin to address this gap in a way that is respectful of community knowledge and needs, the urban gardening research opportunities workgroup (ugrow) project explored the benefits and potential risks of community gardening in southeast toronto. the project used a community-based research (cbr) model to assess community gardens as a means of improving local health. the research process included interviews, focus groups, and participant observation (documented in field notes). we also directly engaged the community in the research process, through co-learning activities and community events which allowed participants to express their views and comment on emerging results. most of the research was conducted by a community-based research associate, herself a community gardener. key results were derived from these various sources through line-by-line coding of interview transcripts and field note review, an interactive and iterative process which involved both academic and community partners. results: these various data sources all suggest that enhanced health and access to fresh produce are important components of the gardening experience. they also highlight the central importance of empowering and community-building aspects of gardening to gardeners. community gardens were thought to play a role in developing friendships and social support, sharing food and other resources, appreciating cultural diversity, learning together, enhancing local place attachment and stewardship, and mobilizing to solve local problems (both inside and outside the garden). potential challenges to community gardens as a mechanism for communiry development include bureaucratic resistance to gardens, insecure land tenure and access, concerns about soil contamination, and a lack of awareness and under· standing by community members and decision-makers of all kinds. conclusion: the results highlight many health and broader social benefits experienced by commu· nity gardeners. they also point to the need for greater support for community gardening programs, par· ticularly ongoing the ongoing provision of resources and education programs to support gardens in their many roles. this research project is supported by the wellesley central health corporation and the centre for urban health initiatives, a cihr funded centre for research development hased at the univer· sity of toronto. p - (c) developing resiliency in children living in disadvantaged neighbourhoods sarah farrell, lorna weigand, and wayne hammond the traditional idea of targeting risk reduction by focusing on the development of eff~ctive coping strategies and educational programs has merit in light of the research reportmg_ that_ ~ lupl.e forms of problem behaviour consistently appear to be predicted by increasing exposure to den_uf able risk factors. as a result, many of the disadvantaged child and youth studies have focused on trymg to better _unde.r· stand the multiple risk factors that increase the likelihood of the development of at nsk behaviour m ch ldren/youth and the potential implications for prevention. this in turn has led t_o. the conclus on that community and health programs need to focus on risk reduction by helpm~ md v duals develop more effective coping strategies and a better understanding of the limitations of cenam pathologies, problematic v poster sessions coping behaviours and risk factors potentially inheren~ in high needs co~unities. ~owever, another ai:ea of research has proposed that preventative interventions should cons de~ .~rotecnve fa~ors alo~~ with reducing risk factors. as opposed to just emphasizing problems, vulnerab ht es, and deficits, a res liencybased perspective holds the belief that children, youth and their families. have strengths, reso~ce.s and the ability to cope with significant adversity in ways that are not only effective, but tend to result m mcreased ability to constructively respond to future adversity. with this in mind, a participatory research project sponsored by the united way of greater toronto was initiated to evaluate and determine the resiliency profiles of children - years (n = ) of recent immigrant families living in significantly disadvantaged communities in the toronto area. the presentation will provide an overview of the identified protective factors (both intrinsic and extrinsic) and resiliency profiles in an aggregated format as well as a summary of how the children and their parents interpreted and explained these strength-based results. as part of the focus groups, current community programs and services were examined by the participants as to what might be best practices for supporting the development and maintaining of resiliency in children, families and communities. it was proposed that the community model of assessing resiliency and protective factors as well as proposed best strength-based practice could serve as a guide for all in the community sector who provide services and programs to those in disadvantaged neighbourhoods. p - (c) naloxone by prescription in san francisco, ca and new york, ny emalie huriaux the harm reduction coalition's overdose project works to reduce the number of fatal overdoses to zero. located in new york, ny and san francisco, ca, the overdose project provides overdose education for social service providers, single-room occupancy hotel (sro) residents, and syringe exchange participants. the project also conducts an innovative naloxone prescription program, providing naloxone, an opiate antagonist traditionally administered by paramedics to temporarily reverse the effects of opiate overdose, to injection drug users (idus). we will describe how naloxone distribution became a reality in new york and san francisco, how the project works, and our results. the naloxone prescription program utilizes multiple models to reach idus, including sro-and street-based trainings, and office-based trainings at syringe exchange sites. trainings include information on overdose prevention, recognition, and response. a clinician conducts a medical intake with participants and provides them with pre-filled units of naloxone. in new york, funding was initially provided by tides foundation. new york city council provides current funding. new york department of mental health and hygiene provides program oversight. while the new york project was initiated in june , over half the trainings have been since march . in san francisco, california endowment, tides foundation, and san francisco department of public health (sfdph) provide funding. in addition, sfdph purchases naloxone and provides clinicians who conduct medical intakes with participants. trainings have been conducted since november . to date, nearly individuals have been trained and provided with naloxone. approximately of them have returned for refills and reported that they used naloxone to reverse an opiate-related overdose. limited episodes of adverse effects have been reported, including vomiting, seizure, and "loss of friendship." in new york, individuals have been trained and provided with naloxone. over overdose reversals have been reported. over half of the participants in new york have been trained in the south bronx, the area of new york with the highest rate of overdose fatalities. in san francisco, individuals have been trained and provided with naloxone. over overdose reversals have been reported. the majority of the participants in san francisco have been trained in the tenderloin, th street corridor, and mission, areas with the highest rates of overdose fatalities. the experience of the overdose project in both cities indicates that providing idus low-threshold access to naloxone and overdose information is a cost-effective, efficient, and safe intervention to prevent accidental death in this population. p - (c) successful strategies to regulate nuisance liquor stores using community mobilization, law enforcement, city council, merchants and researchers tahra goraya presenta~ion _will discuss ~uccessful environmental and public policy strategies employed in one southen: cahf?rmna commumty to remedy problems associated with nuisance liquor stores. participants ~ be given tools to understand the importance of utilizing various substance abuse prevention str~tegi~ to change local policies and the importance of involving various sectors in the community to a~_ st with and advocate for community-wide policy changes. recent policy successes from the commultles of pa~ad~na and altad~na will highlight the collaborative process by which the community mobilized resulnng m several ordmances, how local law enforcement was given more authority to monitor poster sessions v nonconforming liquor stores, how collaborative efforts with liquor store owners helped to remove high alcohol content alcohol products from their establishments and how a community-based organiz,uion worked with local legislators to introduce statewide legislation regarding the regulation of nuisance liquor outlets. p - (c) "dialogue on sex and life": a reliable health promotion tool among street-involved youth beth hayhoe and tracey methven introduction: street involved youth are a marginalized population that participate in extremely risky behaviours and have multiple health issues. unfortunately, because of previous abuses and negative experiences, they also have an extreme distrust of the adults who could help them. in , toronto public health granted funding to a non governmental, nor for profit drop-in centre for street youth aged - , to educate them about how to decrease rhe risk of acquiring hiv. since then the funding has been renewed yearly and the program has evolved as needed in order to target the maximum number of youth and provide them with vital information in a candid and enjoyable atmosphere. methods: using a retrospective analysis of the six years of data gathered from the "dialogue on sex and life" program, the researchers examined the number of youth involved, the kinds of things discussed, and the number of youth trained as peer leaders. also reviewed, was written feedback from the weekly logs, and anecdotal outcomes noted by the facilitators and other staff in the organization. results: over the five year period of this program, many of youth have participated in one hour sessions of candid discussion regarding a wide range of topics including sexual health, drug use, harm reduction, relationship issues, parenting, street culture, safety and life skills. many were new youth who had not participated in the program before and were often new to the street. some of the youth were given specific training regarding facilitation skills, sexual anatomy and physiology, birth control, sexually transmitted infections, hiv, substance use/abuse, harm reduction, relationships and discussion of their next steps/future plans following completion of the training. feedback has been overwhelmingly positive and stories of life changing decisions have been reported. conclusion: clearly, this program is a successful tool to reach street involved youth who may otherwise be wary of adults and their beliefs. based on data from the evaluation, recommendations have been made to public health to expand the funding and the training for peer leaders in order ro target between - new youth per year, increase the total numbers of youth reached and to increase the level of knowledge among the peer leaders. p - (c) access to identification and services jane kali replacing identification has become increasingly more complex as rhe government identification issuing offices introduce new requirements rhar create significant barriers for homeless people to replace their id. new forms of identification have also been introduced that art' not accessible to homekss peoplt-(e.g. the permanent resident card). ar rhe same time, many service providers continue to require identifi· cation ro access supports such as income, housing, food, health care, employment and employmt·nt training programs. street health, as well as a number of other agencies and community health centres, h, , been assisting with identification replacement for homeless peoplt· for a number of years. the rnrrt·nr challenges inherent within new replacement requirements, as well as the introduction of new forn ' of identification, have resulted in further barriers homeless people encounter when rrring to access t:ssential services. street health has been highlighting these issues to government identification issuing offices, as well as policy makers, in an effort to ensure rhar people who are homeless and marginalized have ac'ess to needed essential services. bandar is a somali word for •·a safe place." the bandar research project is the product of the regent park community health centre. the research looks ar the increasing number of somali and afri· can men in the homeless and precariously house population in the inner city core of down~own toronto. in the first phase of the pilot project, a needs assessment was conducted to dennfy barners and issues faced by rhe somali and other african men who are homeless and have add cr ns issues. th_e second phase of rhe research project was to identify long rerm resources and service delivery mechamsms that v poster sessions would enhance the abiity of this population to better access detox, treatment, and post treatment ser· vices. the final phase of the project was to facilitate the development of a conceptual model of seamless continual services and supports from the streets to detox to treatment to long term rehabilitation to housing. "between the pestle and mortar" -safe place. p - (c) successful methods for studying transient populations while improving public health beth hayhoe, ruth ewert, eileen mcmahon, and dan jang introduction: street youth are a group that do not regularly access healthcare because of their mis· trust of adults. when they do access health care, it is usually for issues severe enough for hospitalization or for episodic care in community clinics. health promotion and illness prevention is rarely a part of their thinking. thus, standard public health measures implemented in a more stable population do not work in this group. for example, pap tests, which have dearly been shown to decrease prevalence of cer· vical cancer, are rarely done and when they are, rarely followed up. methods to meet the health care needs and increase the health of this population are frequently being sought. methods: a drop-in centre for street youth in canada has participated in several studies investigating sexual health in both men and women. we required the sponsoring agencies to pay the youth for their rime, even though the testing they were undergoing was necessary according to public health stan· dards. we surmised that this would increase both initial participation and return. results: many results requiring intervention have been detected. given the transient nature of this population, return rates have been encouraging so far. conclusion: it seems evident that even a small incentive for this population increases participation in needed health examinations and studies. it is possible that matching the initial and follow-up incentives would increase the return rate even further. the fact that the youth were recruited on site, and not from any external advertising, indicates that studies done where youth trust the staff, are more likely to be successful. the presentation will share the results of the "empowering stroke prevention project" which incor· porated self-help mutual aids strategies as a health promotion methodology. the presentation will include project's theoretical basis, methodology, outcomes and evaluation results. self-help methodology has proven successful in consumer involvement and behaviour modification in "at risk," "marginalized" settings. self-help is a process of learning with and from each other which provides participants oppor· tunities for support in dealing with a problem, issue, condition or need. self-help groups are mechanisms for the participants to investigate existing solutions and discover alternatives, empowering themselves in this process. learning dynamic in self-help groups is similar to that of cooperative learning and peertraining, has proven successful, effective and efficient (haller et al, ) . the mutual support provided by participation in these groups is documented as contributory factor in the improved health of those involved. cognizant of the above theoretical basis, in the self-help resource centre initiated the "empowering stroke prevention project." the project was implemented after the input from health organizations, a scan of more than resources and an in-depth analysis of risk-factor-specific stroke prevention materials indicated the need for such a program. the project objectives were:• to develop a holistic and empowering health promotion model for stroke prevention that incorporates selfhelp and peer support strategies. • to develop educational materials that place modifiable risk factors and lifestyle information in a relevant context that validates project participants' life experiences and perspectives.• to educate members of at-risk communities about the modifiable risk factors associated with stroke, and promote healthy living. to achieve the above, a diverse group of community members were engaged as "co-editors" in the development of stroke prevention education materials which reflected and validated their life experiences. these community members received training to become lay health promoters (trained volunteer peer facilitators). in collaboration with local health organizations, these trained lay health promoters were then supported in organizing their own community-based stroke prevention activities. in addition, an educational booklet written in plain language, entitled healthy ways to prevent stroke: a guide for you, and a companion guide called healthy ways to pre· vent stroke: a facilitator's guide were produced. the presentation will include the results of a tw<>tiered evaluation of the program methodology, educational materials and the use of the materials beyond the life of the project. this poster presentation will focus on the development and structure of an innovative street outreach service that assists individuals who struggle mental illness/addictions and are experiencing homelessness. the mental health/outreach team at public health and community services (phcs) of hamilton, ontario assists individuals in reconnecting with health and social services. each worker brings to the ream his or her own skills-set, rendering it extremely effective at addressing the multidimensional and complex needs of clients. using a capacity building framework, each ream member is employed under a service contract between public health and community services and a local grassroots agency. there are public health nurses (phn), two of whom run a street health centre and one of canada's oldest and most successful needle exchange programs, mental health workers, housing specialists, a harm reduction worker, youth workers, and a united church minister, to name a few. a community advisory board, composed of consumers and professionals, advises the program quarterly. the program is featured on raising the roors 'shared learnings on homelessness' website at www.sharedlearnings.ca. through our poster presentation participants will learn how to create effective partnerships between government and grassroots agencies using a capacity building model that builds on existing programs. this study aims to assess the effects of broadcasting a series of documentary and drama videos, intended to provide information about the bc healthguide program in farsi, on the awareness about and the patterns of the service usage among farsi-speaking communities in the greater vancouver area. the major goals of the present study were twofold; ( ) to compare two methods of communications (direct vs. indirect messages) on the attitudes and perceptions of the viewers regarding the credibility of messengers and the relevance of the information provided in the videos, and ( ) to compare and contrast the impact of providing health information (i.e., the produced videos) via local tvs with the same materials when presented in group sessions (using vcr) on participants' attitudes and perceptions cowards the bc healrhguide services. results: through a telephone survey, farsi-speaking adults were interviewed in november and december . the preliminary findings show that % of the participants had seen the aired videos, from which, % watched at least one of the 'drama' clips, % watched only 'documentary' clip, and % watched both types of video. in addition, % of the respondents claimed that they were aware about the program before watching the aired videos, while % said they leaned about the services only after watching the videos. from this group, % said they called the bchg for their own or their "hildren's health problems in the past month. % also indicated that they would use the services in the future whenever it would be needed. % considered the videos as "very good" and thought they rnuld deliver relevant messages and % expressed their wish to increase the variety of subjects (produ\:e more videos) and increase the frequency of video dips. conclusion: the results of this study will assist public health specialists in bc who want to choose the best medium for disseminating information and apply communication interventions in multi\:ultural communities. introduction: many theorists and practitioners in community-based research (cbr) and knowledge transfer (kt) strongly advocate for involvement of potential users of research in the development of research projects, yet few examples of such involvement exist for urban workplace health interventions. we describe the process of developing a collaborative research program. methods: four different sets of stakeholders were identified as potential contributors to and users of the research: workplace health policy makers, employers, trade unions, and health and safety associations. representatives of these stakeholders formed an advisory committee which met quarterly. over the month research development period, an additional meetings were held between resc:ar~h~rs and stakeholders. in keeping with participant observation approaches, field notes of group and md v ~ ual meetings were kept by the two co-authors. emails and telephone calls were also documented. qu~h tative approaches to textual analysis were used, with particular attention paid to collaborattve v poster sessions relationships established (as per cbr), indicators of stakeholders' knowledge utilization (as per kt), and transformations of the proposed research (as per cbr). results: despite initial strong differences of opinion both among stakeho~ders .an~ between stakeholders and researchers, goodwill was noted among all involved. acts of rec~proc ty included mu.rual sharing of assessment tools, guidance on data utilization to stakeho~der orga~ zat ns, and suggestions on workplace recruitment to researchers. stakeholders demonstrated mcreases m concep~ual. un~erstand ing of workplace health e.g. they more commonly discussed more complex,. psychosocial md cators of organizational health. stakeholders made instrumental use of shared materials based on research e.g. adapting their consulting model to more sophisticated dat~ analysis. sta~ehol?~rs recogni_zed the strategic use of their alliance with researchers e.g., transformational leadership trainmg as a~ inducement to improve health and safety among small service franchises. stakeholders helped re-define the research questions, dramatically changed the method of recruitment from researcher cold call to stakeholderbased recruitment, and strongly influenced pilot research designs. owing a great deal to the elaborate joint development process, the four collaboratively developed pilot project submissions which were all successfully funded. conclusion: the intensive process of collaborative development of a research program among stakeholders and researchers was not a smooth process and was time consuming. nevertheless, the result of the collaborative process was a set of projects that were more responsive to stakeholder needs, more feasible for implementation, and more broadly applicable to relevant workplace health problems. introduction: environmental groups, municipal public health authorities and, increasingly, the general public are advocating for reductions in pesticide use in urban areas, primarily because of concern around potential adverse health impacts in vulnerable populations. however, limited evidence of the relative merits of different intervention strategies in different contexts exists. in a pilot research project, we sought to explore the options for evaluating pesticide reduction interventions across ontario municipalities. methods: the project team and a multi-stakeholder project advisory committee (pac), generated a list of potential key informants (kl) and an open ended interview guide. thirteen ki from municipal government, industry, health care, and environmental organizations completed face to face or telephone interviews lasting - minutes. in a parallel process, a workshop involving similar representatives and health researchers was held to discuss the role of pesticide exposure monitoring. minutes from pac meetings, field notes taken during ki interviews, and workshop proceedings were synthesized to generate potential evaluation methods and indicators. results: current evaluation activities were limited but all kls supported greater evaluation effons beginning with fuller indicator monitoring. indicators of education and outreach services were imponant for industry representatives changing applicator practices as well as most public health units and environmental organizations. lndictors based on bylaw enforcement were only applicable in the two cities with bylaws, though changing attitudes toward legal approaches were being assessed in many communities. the public health rapid risk factor surveillance system could use historical baseline data to assess changes in community behaviour through reported pesticide uses and practices, though it had limited penetration in immigrant communities not comfortable in english. pesticide sales (economic) data were only available in regional aggregates not useful for city specific change documentation. testing for watercourse or environmental contamination might be helpful, but it is sporadic and expensive. human exposure monitoring was fraught with ethical issues, floor effects from low levels of exposure, and prohibitive costs. clinical episodes of pesticide exposure reported to the regional poison centre (all ages) or the mother risk program (pregnant or breastfeeding women) are likely substantial underestimates that would be need to be supplemented with sentinel practice surveillance. focus on special clinical populations e.g., multiple chemical sensitivity would require additional data collection efforts . . conc~ons: broad support for evaluation and multiple indicators were proposed, though con-s~raints associate~ with access, coverage, sensitivity and feasibility were all raised, demonstrating the difficulty of evaluating such urban primary prevention initiatives. interventionists. an important aim of the youth monitor is to learn more about the health development of children and adolescents and the factors that can influence this development. special attention is paid to emo· tional and behavioural problems. the youth monitor identifies high-risk groups and factors that are associated with health problems. at various stages, the youth monitor chancrs the course of life of a child. the sources of informa· tion and methods of research are different for each age group. the results arc used to generate various kinds of repons: for children and young persons, parents, schools, neighbourhoods, boroughs and the municipality of rotterdam and its environs. any problems can be spotted early, at borough and neigh· bourhood level, based on the type of school or among the young persons and children themselves. together with schools, parents, youngsters and various organisations in the area, the municipal health service aims to really address these problems. on request, an overview is offered of potentially suitable interventions. the authors will present the philosophy, working method, preliminary effects and future developments of this instrument, which serves as the backbone for the rotterdam local youth policy. social workers to be leaders in response to aging urban populations: the practicum partnership program sarah sisco, alissa yarkony, and patricia volland "'" tliu:tion: across the us, . % of those over live in urban areas. these aging urban popu· lations, including the baby boomers, have already begun encounter a range of heahh and mental hcahh conditions. to compound these effects, health and social service delivery fluciuates in cities, whit:h arc increasingly diverse both in their recipients and their systems. common to other disciplines (medicine, nursing, psychology, etc.) the social work profession faces a shortage of workers who are well-equipped to navigate the many systems, services, and requisite care that this vast population requires. in the next two decades, it is projected that nearly , social workers will be required to provide suppon to our older urban populations. social workers must be prepared to be aging-savvy leaders in their field, whether they specialize in gerontology or work across the life span. mllhotu: in , a study conducted at the new york academy of medicine d<> :umcntcd the need for improved synchroniciry in two aspects of social work education, classroom instruction and the field experience. with suppon from the john a. hanford foundation, our team created a pilot proj~"t entitled the practicum pannership program (ppp) in master's level schools of social work, to improvt" aginr exposure in field and classroom content through use of the following: i) community-university partnrr· ships, ) increased, diverse student field rotations, ll infusion of competcn ."}'·drivm coursework, enhancement of field instructors' roles, and ) concentrated student recruitment. we conductt"d a prr· and post-test survey into students' knowledge, skills. and satisfaction. icarlja: surveys of over graduates and field inltnk."tors rcflected increased numlk-n of . rrm:y· univmity panncrships, as well as in students placed in aging agencin for field placements. there wa marked increase in student commitments to an aging specialization. onr year por.t·gradu:nion rcvealrd that % of those surveyed were gainfully employed, with % employed in the field of aginic. by com· bining curricular enhancement with real-world experiences the ppp instilled a broad exposurr for llu· dents who worked with aging populations in multiple urban settings. coltdtuion: increased exposure to a range of levels of practicr, including clinical, policy/ajvocaq, and community-based can potentially improve service delivery for older adulh who live in elfin, and potentially improve national policy. the hanford foundation has now elected to uppon cxpantion of the ppp to schools nationwide (urban and rural) to complement other domntic initiatives to cnhalk"c" holistic services for older adults across the aging spectrum. bodrgnn.ntl: we arc a team of rcscarcbcn and community panncn working tcj c(her to develop an in"itepth understanding of the mental health needs of homeless youth ~ages to ) (using qualiutivc and quantitative methods ' panicipatory rncarch methods). it is readily apparmt that '-neless youth cxpcricnce a range of mental health problems. for youth living on the street, menul illnew may be either a major risk factor for homelessnal or may frequently emcsge in response to coping with rhe multitudinous stressors associated with homclcslllcsi including exposure to violence, prasutt to pamaplte in v poster sessions survival sex and/or drug use. the most frequent psychiatric diagnoses amongst the homeless gencrally include: depression, anxiety and psychosis. . . . the ultimate ob ective of the pr~am of rei:e~ is to ~evelop a plan for intervention to meet the mental health needs of street youth. prior t_o pl~nnmg mtervenbons, .it is necessary to undertake a comprehensive assessment ~f mental health needs m this ~lnerable populanon. thus, the immediate objective of this research study is to undertake a comprehensive assessment of men· tal health needs. . . melbotlology: a mixed methodology triangulating qualitative, participatory acnon and quantitative methods will capture the data related to mental health needs of homeless youth. a purposive sample of approximately - subjecrs. ages to , is currently being ~ted ~participate from the commu.nity agencies covenant house, evergreen centre fo~ srrc;et youth, turning p? ?t and street ~ serv~. youth living on the street or in short -term residennal programs for a mmimum of month pnor to their participation; ages to and able to give infonned consent will be invited to participate in the study. o..tcomes: the expected outcome of this initial survey will be an increased understanding of mental health needs of street youth that will be used to develop effective interventions. it is anticipated that results from this study will contribute to the development of mental health policy, as well as future programs that are relevant to the mental health needs of street youth. note: it is anticipated that preliminary quantitative data ( subjects) and qualitative data will be available for the conference. the authors intend to present the identification of the research focus, the formation of our community-based team, relevance for policy, as well as preliminary results. p - (a) the need for developing a firm health policy for urban informal worken: the case of despite their critical role in producing food for urban in kenya, urban farmers have largely been ignored by government planners and policymakers. their activity is at best dismissed as peripheral eveo, inappropriate retention of peasant culture in cities and at worst illegal and often some-times criminal· ized. urban agriculture is also condemned for its presumed negative health impact. a myth that contin· ues despite proof to the contrary is that malarial mosquitoes breed in maize grown in east african towns. however, potential health risks are insignificant compared with the benefits of urban food production. recent studies too rightly do point to the commercial value of food produced in the urban area while underscoring the importance of urban farming as a survival strategy among the urban poor, especially women-headed households. since the millennium declaration, health has emerged as one of the most serious casualties consequent on the poverty, social exclusion, marginalisation and lack of sustain· able development in africa. hiv/aids epidemic poses an unprecedented challenge, while malaria, tuber· culosis, communicable diseases of childhood all add to the untenable burden. malnutrition underpins much ill-health and is linked to more than per cent of all childhood deaths. kenya's urban poor people ~ace ~ h~ge burde~ of preventable and treatable health problems, measured by any social and bi~ medical md cator, which not only cause unnecessary death and suffering, but also undermine econonuc development and damage the country's social fabric. the burden is in spite of the availability of suitable tools and re:c=hnology for prevention and treatment and is largely rooted in poverty and in weak healah •rstems. this pa~ therefore challenges development planners who perceive a dichotomy instead of con· tmuum between informal and formal urban wage earners in so far as access to health services is con· cemed. it i~ this gap that calls for a need to developing and building sustainable health systems among the urban mformal ~wellers. we recommend a focus on an urban health policy that can build and strengthen the capacity of urban dwellers to access health services that is cost-effective and sustainable. such ~ health poli<=>: must strive for equity for the urban poor, displaced or marginalized; mobilise and effect ~ely use sufficient sustainable resources in order to build secure health systems and services. special anenti_on. should ~ afforded hiv/aids in view of the unprecedented challenge that this epidemic poses to africa s economic and social development and to health services on the continent. methods: a review of the literature led us to construct three simple models and a composite model of exposure to traffic. the data were collected with the help of a daily diary of travel activities using a sample of cyclists who went to or come back from work or study. to calculate the distance, the length of journey, and the number of intersections crossed by a cyclist different geographic information systems (gis) were operated. statistical analysis was used to determine the significance between a measure of exposure on the one hand, and the sociodemographic characteristics of the panicipants or their geographic location on the other hand. restlltj: our results indicate that cyclists were significantly exposed to road accidents, no matter of where they live or what are their sociodemographic characteristics. we also stress the point that the fact of having been involved in a road accident was significantly related to the helmet use, but did not reduce the propensity of the cyclists to expose themselves to the road hazards. condlllion: the efforts of the various authorities as regards road safety should not be directed towards the reduction of the exposure of the vulnerable users, but rather towards the reduction of the dangers to which they could face. keywords: cyclist, daily diary of activities, measures of exposure to traffic, island of montreal. p - (a) intra urban disparities and environmental health: some salient features of nigerian residential neighbourhoods olumuyiwa akinbamijo intra urban disparities and environmental health: some salient features of nigerian residential neighbourhoods abstract urbanization panicularly in nigerian cities, ponends unprecedented crises of grave dimensions. from physical and demographic viewpoints, city growth rates are staggering coupled with gross inabilities to cope with the consequences. environmental and social ills associated with unguarded rapid urbanization characterize nigerian cities and threaten urban existence. this paper repons the findings of a recent study of the relationship between environmental health across inrraurban residential communities of akure, south west nigeria. it discuses the typical urbanization process of nigerian cities and its dynamic spatial-temporal characteristics. physical and socio-demographic attributes as well as the levels and effectiveness of urban infrastructural services are examined across the core residential districts and the elite residential layouts in the town. the incidence rate of cenain environmentally induced tropical diseases across residential neighborhoods and communes is examined. salient environmental variables that are germane to health procurement in the residential districts, incidence of diseases and diseases parasitology, diseases prevention and control were studied. field data were subjected to analysis ranging from the univariate and bivariate analysis. inferential statistics using the chi-square test were done to establish the truthfulness of the guiding hypothesis. given the above, the study affirms that there is strong independence in the studied communities, between the environment and incidence of diseases hence health of residents of the town. this assertion, tested statistically at the district levels revealed that residents of the core districts have very strong independence between the environment and incidences of diseases. the strength of this relationship however thins out towards the city peripheral districts. the study therefore concludes that since most of the city dwellers live in urban deprivation, urban health sensitive policies must be evolved. this is to cater for the urban dwellers who occupy fringe peripheral sites where the extension of facilities often times are illegally done. urban infrastructural facilities and services need be provided as a matter of public good for which there is no exclusive consumption or access even for the poorest of the urban poor. many suffer from low-self esteem, shame and guilt about their drug use. in addition, they often lack suppon or encounter opposition from their panners, family and friends in seeking treatment. these personal barriers are compounded by fragmented addiction, prenatal and social care services, inflexible intake systems and poor communication among sectors. the experience of accessing adequate care between services can be overwhelming and too demanding. the toronto centre for substance use in pregnancy (t-cup) is a unique program developed to minimize barriers by providing kone-stop" comprehensive healthcare. t-cup is a primary care based program located in the department of family medicine at st. joseph\'s health centre, a community teaching hospital in toronto. the interdisciplinary staff provides prenatal and addiction services, case management, as well as care of newborns affected by substance use. regular care plan meetings are held between t-cup, labour and delivery nurses and social workers in the y poster sessions maternity and child care program. t-cup also connects "'.omen with. inpatient treatment programs and community agencies such as breaking the cycle, an on-site counselmg group for pregnant substance users. · f · d d h ith method: retrospective chart review, qualitative patient ~ans action stu ~· an ea care provider surveys are used to determine outcomes. primary outcomes mclude changes m maternal su~tance use, psychosocial status and obstetrical complications (e.g. pre-rupture of membrane, pre-eclampsia, placen· ral abruption and hemorrhage). neonatal measures ~~nsisted of .bir~h pa_rame~ers, length of h~spital st.ay and complications (e.g. feral distress, meconium stammg, resuscitation, aund ce, hypoglycemia, seventy of withdrawal and treatment length). chart review consisted of all t-cup patients who met clinical cri· reria for alcohol or drug dependence and received prenatal and intra-partum care at st. joseph's from october to june . participants in the qualitative study included former and current t-cup patients. provider surveys were distributed on-site and to a local community hospital. raulb: preliminary evaluation has demonstrated positive results. treatment retention and satisfaction rates were high, maternal substance use was markedly reduced and neonatal outcomes have shown to be above those reported in literature. conclusion: this comprehensive, primary care model has shown to be optimal in the management of substance use in pregnancy and for improving neonatal outcomes. future research will focus on how this inexpensive program can be replicated in other health care settings. t-cup may prove to be the optimal model for providing care to pregnant substance users in canada. lntrod ction: cigarette smoking is one of the most serious health problems in taiwan. the prevalence of smoking in is . % in males . % in females aged years and older. although the government of taiwan passed a tobacco hazards control act in , it has not been strongly enforced in many places. therefore, community residents have often reported exposure of second hand smoke. the purpose of the study was to establish a device to build up more smoke-free environments in the city of tainan. methods: unique from traditional intervention studies, the study used a healthy city approach to help build up smoke-free environments. the major concept of the approach is to build up a healthy city platform, including organizing a steering committee, setting up policies and indicators, creating intersectoral collaboration, and increasing community participation. first, more than enthusiastic researchers, experts, governmental officers, city counselors and community leaders in tainan were invited in the healthy city committee. second, smoke-free policies, indicators for smoke-free environments, and mechanisms for inter-departmen· tal inspections were set up. third, community volunteers were recruited and trained for persuading related stakeholders. lastly, both penalties and rewards were used for help build up the environments. raults: aher two-year ( aher two-year ( - execution of the project, the results qualitatively showed that smoke-free environments in tainan were widely accepted and established, including smoke-free schools, smoke-free workpla~es, smoke-free households, smoke-free internet shops, and smoke-free restaurants. smoke~s were. effectively educated not to smoke in public places. community residents including adults and children m the smoke-free communities clearly understand the adverse effects of environmental tobacco smoke and actively participated anti-smoking activities. conclruions: healthy city platform is effective to conquer the barrier of limited anti-smoking rc:sources. nor. only can it enlar:ge community actions for anti-smoking campaigns, but also it can provide par_merships for collaboratjon. by establishing related policies and indicators the effects of smoke· free environments can be susta ·ned a d th · · · ' · n e progression can be monitored m a commuruty. these issues are used ~· oi::c it~ goals, weuha identifies issues that put people's health at risk. presently, team com~u:c: ran ee~tion !earns. (iats) that design integrative solutions ~tesj'°~ g om six to fifteen members. methods in order to establish wo-poster sessions v projects for weuha, the following approach was undertaken: i. a project-polling template was created and sent to all members of the alliance for their input. each member was asked to identify thdr top two population groups, and to suggest a project on which to focus over a - month period for each identified population. . there was a % response to the poll and the top three population groups were identified. data from the toronto community health profile database were utilized to contextualize the information supplied for these populations. a presentation was made to the steering committee and three population-based projects were selected, leaders identified and iats formed. three population-based projects: the population-based projects and health care issues identified are: newcomer prenatal uninsured women; this project will address the challenges faced by providers to a growing number of non-insured prenatal women seeking care. a service model where the barrier of "catchments" is removed to allow enhanced access and improved and co-ordinated service delivery will be pilot-tested. children/obesity/diab etes: using a health promotion model this team will focus on screening, intervention, and promoting healthy lifestyles (physical activity and nutrition) for families as well as for overweight and obese children. seniors health promotion and circle of discharge: this team will develop an early intervention model to assist seniors/family unit/caregivers in accessing information and receiving treatment/care in the community. the circle of discharge initiative will address ways of utilizing community supports to keep seniors in the community and minimize readmissions to acute care facilities. results/expected outcomes: coordinated and enhanced service delivery to identified populations, leading to improved access, improved quality of life, and health care for these targeted populations. introduction: basic human rights are often denied to high-risk populations and people living with hiv/aids. their rights to work and social security, health, privacy, non discrimination, liberty and freedom of movement, marriage and having a family have been compromised due to their sero-positive status and risk of being positive. the spread of hiv/aids has been accelerating due to the lack of general human rights among vulnerable groups. to formulate and implement effective responses needs dialogue and to prevent the epidemic to go underground barriers like stigma need to be overcome. objective: how to reduce the situation of stigma, discrimination and human rights violations experienced by people living with hiv/aids and those who are vulnerable to hiv/aids. methodology and findings: consultation meetings were strm.-rured around presentations, field visits, community meetings and group work to formulate recommendations on how govt and ngos/cbos should move forward based on objective. pakistan being a low prevalence country, the whole sense of compl;u:enc.:y that individuals are not subject to situations of vulnerable to hiv is the major threat to an explosion in th•· epidemic, therefore urgent measures are needed to integrate human rights issues from the very start of the response. the protection and promotion of human rights in an integral component of ;tll responses to the hiv/aids epidemic. it has been recognized that the response to hiv/aios must he multi sectoral and multi faceted, with each group contributing its particular expertise. for this to occur along with other knowlcdg<" more information is required in human rights abuses related to hiv/ aids in a particular scenario. the ~·on sultarion meetings on hiv/aids and human rights were an exemplary effort to achieve the same ohj<..:tivc. recommendations: the need for a comprehensive, integrated and a multi-sectoral appro;u.:h in addressing the issue of hiv/aids was highlighted. the need social, cultural and religious asp•·ct' to he: prominently addressed were identified. it was thought imperative measures even in low prevalence countries. education has a key role to play, there is a need for a code of ethics for media people and h<"alth care providers and violations should be closely monitored and follow up action taken. p - (c) how can community-based funding programs contribute to building community capacity and how can we measure this elusive goal? mary frances maclellan-wright, brenda cantin, mary jane buchanan, and tammy simpson community capacity building is recognized by the public health agency of canada (phac) as an important strategy for improving the overall health of communities by enabling communities to addre~s priority issues such as social and economic determinants of health. in / phac.:, alberta/nwf region's population health fund (phf) supported community-based projects to build community capacity on or across the determinants of health. specifically, this included creating accessible and sup· portive social and physical environments as well as creating tools and processes necessary for healthy policy development and implementation. the objective of this presentation is to highlight how the community capacity building tool, developed by phac ab/nwf region, can demonstrate gains in v poster sessions · · the course of a pror· ect and be used as a reflective tool for project planning and community capacity over . . . . i · a art of their reporting requirements, pro ect sites completed the community caparny eva uanon. s p . . th t i ii i'd d . building tool at the beginning and end of their ~ne-year prorect. e oo ~o ects va an reliable data in the context of community-based health prorects. developed through a vigorous ~nd collabora ve research process, the tool uses plain languag~ to expl~re nine key f~atures o~ commuruty cap~city with 't ch with a section for contextual information, of which also mdude a four-pomt raong ems, ea f fu d · scale. results show an increase in community capacity over the course o the nde prorects. pre and post aggregate data from the one-year projects measure~ statistic.ally si~n~ficant changes for of the scaled items. projects identified key areas of commumty capacity bmldmg that needed strengthemng, such as increasing participation, particularly among people with low incomes; engaging community members in identifying root causes; and linking with community groups. in completing the tool, projects examined root causes of the social and economic determinants of health, thereby exploring social justice issues related to the health of their community. results of the tool also served as a reflec· cion on the process of community capacity building; that is, how the project outcomes were achieved. projects also reported that the tool helped identify gaps and future directions, and was useful as a project planning, needs assessment and evaluation tool. community capacity building is a strategy that can be measured. the community capacity building tool provides a practical means to demonstrate gains in community capacity building. strengthening the elements of community capacity building through community-based funding can serve as building blocks for addressing other community issues. needs of marginalized crack users lorraine barnaby, victoria okazawa, barb panter, alan simpson, and bo yee thom background: the safer crack use coalition of toronto (scuc) was formed in in response to the growing concern for the health and well-being of marginalized crack users. a central concern was the alarm· ing hepatitis c rate ( %) amongst crack smokers and the lack of connection to prevention and health ser· vices. scuc is an innovative grassroots coalition comprised of front-line workers, crack users, researcher! and advocates. despite opposition and without funding, scuc has grown into the largest crack specific harm reduction coalition in canada and developed a nationally recognized sarer crack kit distribution program (involving community-based agencies that provide outreach to users). the success of our coalition derives from our dedication to the issue and from the involvement of those directly affected by crack use. setting: scuc's primary service region is greater toronto, a diverse, large urban centre. much ofour work is done in areas where homeless people, sex trade workers and drug users tend to congregate. recently, scuc has reached out to regional and national stakeholders to provide leadership and education. mandate: our mandate is to advocate for marginalized crack users and support the devdopmentof a com.p.rehensive harm reduction model that addresses the health and social needs facing crack users; and to fac htare the exchange of information between crack users, service providers, researchers, and policy developers across canada. owrview: the proposed workshop will provide participants with an overview of the devdopment of scuc, our current projects (including research, education, direct intervention and consultation), our challenge~ and s~ccesses and the role of community development and advocacy within the coalition. pre-senter~ will consist of community members who have personal crack use experience and front-line work· ers-, sc.uc conducted a community-based research project (toronto crack users perspectives, ) , in w~ich s focus groups with marginalized crack users across toronto were conducted. participants iden· t f ed health and social issues affecti h b · · · d " red . . ng t em, arrsers to needed services, personal strategies, an oue recommendations for improved services. presenters will share the methodology, results and recommen· datmns resulting from the research project. conc/usio": research, field observations and consultations with stakeholders have shown that cradck shmoke~s are at an. increased risk for sexually transmitted infections hiv/aids hepatitis c, tb an ot er serious health issues health · ff, · ' ' · · . · issues a ectmg crack users are due to high risk behavmurs, socio· economic factors, such as homeless d. · · · · d · . . ness, scrsmmat on, unemployment, violence incarceraoons, an soc a so at on, and a lack of comprehe · h i h · ' ns ve ea t and social services targeting crack users. · · sinct · s, owever arge remains a gross underesurnaoon. poster sessions v these are hospital-based reports and many known cases go unreported. however teh case, young age at first intercourse, inconsistent condom use and multiple partnersplace adolescents at high risks for a diverse array of stls, including hiv. about % of female nigerian secondary school students report initiating sexual intercourse before age years. % of nigerian female secondary school students report not using a condom the last time they had sexual intercourse. more than % of urban nigerian teens report inconsistent condom use. methods: adolescents were studied, ages to , from benin city in edo state. the models used were mother-daughter( ), mother -son( ), father -son ( ), and father-daughter( ). the effect of parent-child sexual communicationat baseline on child\'s report of sexual behavior, to months later were studied. greater amounts of sexual risk communication were asociated with markedly fewer episodes of unprotected sexual intercourse, reduced number of sexual partners and fewer episodes of unprotected sexual intercourse. results: this study proved that parents can exert more influence on the sexual knowledge attitudes and practise of their adolescent children through desired practises or rolemodeling, reiterating their values and appropriate monitoring of the adolescents\' behavior. they also stand to provide information about sexuality and various sexual topics. parental-child sexual communication has been found to be particularly influential and has been associated with later onset of sexual initiation among adolescents, less sexual activity, more responsible sexual attitudes including greater condom use, self efficacy and lower self -reported incidence of stis. conclusions: parents need to be trained to relate more effectively with their children/wards about issues related to sex and sexuality. family -based programs to reduce sexual risk-taking need to be developed. there is also the need to carry out cross-ethnicaland cross-cultural studies to identify how parent-child influences on adolescent sexual risk behavior may vary in different regions or countries, especially inthis era of the hiv pandemic. introduction: public health interventions to identify and eliminate health disparities require evidence-based policy and adequate model specification, which includes individuals within a socioecological context, and requires the integration of biosociomedical information. multiple public and private data sources need to be linked to apportion variation in health disparities ro individual risk factors, the health delivery system, and the geosocial environment. multilevel mapping of health disparities furthers the development of evidence-based interventions through the growth of the public health information network (phin-cdc) by linking clinical and population health data. clinical encounter data, administrative hospital data, population socioenvironmental data, and local health policy were examined in a three-level geocoded multilevel model to establish a tracking system for health disparities. nj has a long established political tradition of "home rule" based in elected municipal governments, which are responsible for the well-being of their populations. municipalities are contained within counties as defined by the us census, and health data are linked mostly at the municipality level. marika schwandt community organizers from the ontario coaliti~n again~t pove~, .along ":ith ~edical practitioners who have endorsed the campaign and have been mvolved m prescnbmg special diet needs for ow and odsp recipients, will discuss the raise the rates campaign. the organizati~n has used a special diet needs supplement as a political tool, meeting the urgent needs o.f .poor ~ople m toront~ while raising the issues of poverty as a primary determinant of health and nutrtnous diet as a preventative health mea· sure. health professionals carry the responsibility to ensure that they use all means available to them to improve the health of the individuals that they serve, and to prevent future disease and health conditions. most health practitioners know that those on social assistance are not able to afford nutritious foods or even sufficient amounts of food, but many are not aware of the extra dietary funds that are available aher consideration by a health practitioner. responsible nurse practitioners and physicians cannot, in good conscience, ignore the special needs diet supplement that is available to all recipients of welfare and disabiliry (ow and odsp). a number of toronto physicians have taken the position that all clients can justifiably benefit from vitamins, organic foods and high fiber diets as a preventative health measure. we know that income is one of the greatest predictors of poor health. the special needs diet is a health promotion intervention which will prevent numerous future health conditions, including chronic conditions such as cardiovascular disease, cancer, diabetes and osteoporosis. many communiry health centres and other providers have chosen to hold clinics to allow many patients to get signed up for the supplement at one time. initiated by the ontario coalition against poverty, these clinics have brought together commu· niry organizers, community health centers, health practitioners, and individuals, who believe that poverty is the primary determinant of poor health. we believe that rates must be increased to address the health problems of all people on social assistance, kids, elders, people with hiv/aids -everyone. even in the context of understaffing, it could be considered a priority activity that has potentially important health promotion benefits. many clients can be processed in a two hour clinic. most providers find it a very interesting, rewarding undertaking. in the ontario coalition for social justice found that a toronto family with two adults and two kids receives $ , . this is $ , below the poverty line. p - (c) the health of street youth compared to similar aged youth beth hayhoe and ruth ewert . lntrod~on: street youth are at an age normally associated with good health, but due to their risky ~hav ours and th~ conditions in which they live, they experience health conditions unlike their peer~ an more stable env r~nments. in addition, the majority of street youth have experienced significant physical, sexual ~nd em.ot onal abuse as younger children, directly impacting many of the choices they make around their physical and emotional health. we examined how different their health really is. . , methodl: using a retrospective analysis of the years of data gathered from yonge street mis· ~ • evergreen health centre, the top conditions of youth were examined and compared with national tren~s for similar aged youth. based on knowledge of the risk factors present in the group, rea· sons for the difference were examined. d' ~its: street youth experience more illness than other youth their age and their illnesses can bt . irect t ·~kc~ to the. conditions in which they live. long-term impacts of abus~ contribute to such signif· ~~nt t e t d~slpl air that youth may voluntarily engage in behaviours or lack of self care in the hope at t cir ve~ w perhaps come to a quicker end. concl non: although it has ion b k h th' dy clearly shows d'fi . h g ee~ no~n t at poverty negatively affects health, ~siu be used to make ; erence m t .e health of this particular marginalized population. the infonnanon can relates to th . ecommendatio.ns around public policy that affects children and youth, especially as it e r access to appropriate health care and follow up. p - (cl why do urban children · b gt . tarek hussain an adesh die: how to save our children? the traditional belief that urban child alid. a recent study (dhs d fr r~n are better off than rural children might be no longer v urban migrants are highata th om h c~untn~s i demonstrates that the child survival prospects of rural· er an t ose m their r j · · ·grants. in bangladesh, currently million ~r~ ~ gm and lower than those of urban non-idi million. health of the urban ~ p~e are hvmg m urban area and by the year , it would be so the popu at on s a key a eals that urban poor have the worse h h . concern. recent study on the urban poor rev ea t situation than the nation as a whole. this study shows that infant poster sessions v mortality among the urban poor as per thousand, which are above the rural and national level estimates. the mortality levels of the dhaka poor are well above those of the rest of the city's population but much of the difference in death rates is explained by the experience of children, especially infants. analyzing demographic surveillance data from a large zone of the city containing all sectors of the population, research showed that the one-fifth of the households with the least possessions exhibited u child mortality almost three times as high as that recorded by the rest of the population. why children die in bangladesh? because their parents are too poor to provide them with enough food, clean water and other basic needs to help them avoid infection and recover from illness. researchers believed that girls are more at risk than boys, as mothers regularly feed boys first. this reflects the different value placed on girls and boys, as well as resources which may not stretch far enough to provide for everyone. many studies show that housing conditions such as household construction materials and access to safe drinking water and hygienic toilet facilities are the most critical determinants of child survival in urban areas of developing countries. the present situation stressed on the need for renewed emphasis on maternal and child healthcare and child nutrition programs. mapping path for progress to save our children would need be done strategically. we have the policies on hand, we have the means, to change the world so that every child will survive and has the opportunity to develop himself fully as a healthy human being. we need the political will--courage and determination to make that a reality. p - (c) sherbourne health centre: innovation in healthcare for the transgendered community james read introduction: sherbourne health centre (shc), a primary health care centre located in downtown toronto, was established to address health service gaps in the local community. its mission is to reduce barriers to health by working with the people of its diverse urban communities to promote wellness and provide innovative primary health services. in addition to the local communities there are three populations of focus: the lesbian, gay, bisexual, transgendered and transexual communities (lgbtt); people who are homeless or underhoused; and newcomers to canada. shc is dedicated to providing health services in an interdisciplinary manner and its health providers include nurses, a nurse practitioner, mental health counsellors, health promoters, client-resource workers, and physicians. in january shc began offering medical care. among the challenges faced was how to provide responsive, respectful services to the trans community. providers had considerable expertise in the area of counselling and community work, but little in the area of hormone therapy -a key health service for those who want to transition from one gender to another. method: in preparing to offer community-based health care to the trans community it was clear that shc was being welcomed but also being watched with a critical eye. trans people have traditionally experienced significant barriers in accessing medical care. to respond to this challenge a working group of members of the trans community and health providers was created to develop an overall approach to care and specific protocols for hormone therapy. the group met over a one year period and their work culminated in the development of medical protocols for the provision of hormone therapy to trans individuals. results: shc is currently providing health care to registered clients who identify as trans individuals (march ) through primary care and mental health programs. in an audit of shc medical charts (january to september ) female-to-male (ftm) and male-to-female (mtf) clients were identified. less than half of the ftm group and just over two-thirds of the mtf group presented specifically for the provision of hormones. based on this chart audit and ongoing experience shc continues to update and refine these protocols to ensure delivery of quality care. conclusion: this program is an example of innovative community-based health delivery to a population who have traditionally faced barriers. shc services also include counselling, health promotion, outreach and education. p - (c) healthy cities for canadian women: a national consultation sandra kerr, kimberly walker, and gail lush on march , the national network on environment and women's health held a pan-canadian consultation to identify opportunities for health research, policy change, and action. this consultation also worked to facilitate information sharing and networking between canadian women working as urban planners, policy makers, researchers, and service workers on issues pertaining to the health of women living in canadian cities. methods: for this research project, participants included front-line service workers, policy workers, researchers, and advocates from coast to coast, including francophone women, women with disabilities, racialized women, and other marginalized groups. the following key areas were selected as topics for du.bnes i alto kading .:auk of end·sugr ieaal clileue ia singapore, accounting for more than so% of new can singapore (nkfs) to embark on a prevention program (pp) empo~r d ahc j u f dieir condition bttter, emphasizing education and disease sdf·managemen lkilla a. essennal camponenn of good glycaemic control. we sought explore the effects of a pecialijed edu.:a on pro· pun od glycacmic conuol, as indicated by, serum hba ic values budine serum hba ic values were determined before un<k-rgmng the education progr ;am, which couisted of comprehensive dietary advice, ideal weight goals, and improving lipid profiln. serum hbaic values were obtained ar , , months later to determine impact of the program. analy • wu done uling paired !·tests significant reduction in hba le levels from ro month• was observed in females, chinese race, older age group(> so yean). ohew-ibmi ~ .nwm , wai hip ratio> l),up to primary and above secondary level education and those having om urine iclt showed that increasing hbalc levels ( ) had increasing urmary protein ( .± ; . ±i ih so± ) and crearinine (s .s ± s ± ; ioi± s) levels fbg rnults showed that the management nf d abetn m the nkfs preven· tion programme is effec;rive. results also indicated har hba le leve have a linnr trend wnh unnary protein and creatinine which are imponant determinants of renal diseate tal family-focused cinical palbway promoce politivc outcollln for ua inner city canu allicy ipmai jerrnjm care llctivirits in preparation for an infanr'' dilchargr honlr, and art m endnl lo improve effi.:k'fl.:tn of c.are. lere i paucity of tttran:h, and inconsi trncy of rnulta on ht-•m!*- of f m ly·fc"-'uw d nm a: to determinr whrthrr implrmentation of family.focuted c:pt n ntnn.tt.tl unit w"n mg an inner city ;ommunity drcl't'aki leftarh of lf•y (i.osi and rromclll'i family uo•fkllon and rt. j nest for dikhargr. md odt: family-focuk"d cpi data wm coll«ted for all infant• horn btrwttn and wft"k• t"lal mi atr who wrtt . dm ed to the ntonatal unit lmgdl of -.y . n. . day'o p c o.osi ind pma . d•mr., ho.nr . t . n. . ± i. i wb, p < o.os) wett n« fiamly f.lfrt n the pre.(]' poup. ~ .fxtmon icofn for famihn wrre high. and families noctd thc:y wnr mott prepued to ah thrar t..lby "'-· thett was .a cosi uving of s , (cdn) per patient d teharpd home n the pmi-cp poap c.-pated the p"''lfoup· cortclaion· lmplrmrnr.rion of family·foanrd c:p. in a nrona . i umt tc"fyidi an nnn an com· muniry decre.ned length of'"'" mft with a high dcgrft of family uujamon, and wrre coll~nt at least % percent of the kathmandu population lives in slum like conditions with poor access to basic health services. in these disadvantaged areas, a large proportion of children do not receive treatment due to inaccessibility to medical services. in these areas, diarrhea, pneumonia, and measles, are the key determinants of infant mortality. protein energy malnutrition and vitamin a deficiency persists and communicable diseases are compounded by the emergence of diseases like hiv/aids. while the health challenges for disadvantaged populations in kathmandu are substantial, the city has also experienced various forms of innovative and effective community development health programs. for example, there are community primary health centers established by the kathmandu municipality to deliver essential health services to targeted communities. these centers not only provide equal access to health services to the people through an effective management system but also educate them hy organizing health related awareness programs. this program is considered one of the most effective urban health programs. the paper/presentation this paper will review large, innovative, and effective urhan health programs that are operating in kathmandu. most of these programs are currently run by international and national ngos a) early detection of emerging diseases in urban settings through syndromic surveillance: data pilot study kate bassil of community resources, and without adequate follow-up. in november shelter pr.oviders ~et with hospital social workers and ccac to strike a working group to address some of th~ issues by mcre.asing knowledge among hospital staff of issues surrounding homelessness, and to build a stro?g workmg relationship between both systems in hamilton. to date the hswg has conducted four w~lkmg to~ of downtown shelters for hospital staff and local politicians. recently the hswg launched its ·~ool.k t for staff working with patients who are homeless', which contains community resources and gu dehnes to help with effective discharge plans. a scpi proposal has been submitted to incre~se the capacity of the hswg to address education gaps and opportunities with both shelters and hospitals around homelessness and healthcare. the purpose of this poster presentation is to share hamilton's experience and learnings with communities who are experiencing similar issues. it will provide for intera~tion around shared experiences and a chance to network with practitioners across canada re: best practices. introduction and objectives: canadians view health as the biggest priority for the federal government, where health policies are often based on models that rely on abstract definitions of health that provide little assistance in the policy and analytical arena. the main objectives of this paper are to provide a functional definition of health, to create a didactic model for devising policies and determining forms of intervention, to aid health professionals and analysts to strategize and prioritize policy objectives via cost benefit analysis, and to prompt readers to view health in terms of capacity measures as opposed to status measures. this paper provides a different perspective on health, which can be applied to various applications of health such as strategies of aid and poverty reduction, and measuring the health of an individual/ community/country. this paper aims to discuss theoretical, conceptual, methodological, and applied implications associated with different health policies and strategies, which can be extended to urban communities. essentially, our paper touches on the following two main themes of this conference: •health status of disadvantaged populations; and •interventions to improve the health of urban communities.methodology: we initially surveyed other models on this topic, and extrapolated key aspects into our conceptual framework. we then devised a theoretical framework that parallels simple theories of physkal energy, where health is viewed in terms of personal/societal health capacities and effort components.after establishing a theoretical model, we constructed a graphical representation of our model using selfrated health status and life expectancy measures. ultimately, we formulated a new definition of health, and a rudimentary method of conducting cost benefit analysis on policy initiatives. we end the paper with an application example discussing the issues surrounding the introduction of a seniors program.results: this paper provides both a conceptual and theoretical model that outlines how one can go about conducting a cost-benefit analysis when implementing a program. it also devises a new definition and model for health barred on our concept of individual and societal capacities. by devising a definition for health that links with a conceptual and theoretical framework, strategies can be more logically constructed where the repercussions on the general population are minimized. equally important, our model also sets itself up nicely for future microsimulation modeling and analysis.implications: this research enhances one's ability to conduct community-based cost-benefit analysis, and acts as a pedagogical tool when identifying which strategies provide the best outcome. p - (a) good playgrounds are hard to find: parents' perceptions of neighbourhood parks patricia tucker, martin holmes, jennifer irwin, and jason gilliland introduction: neighbourhood opportunities, including public parks and physical activity or sports fields hav~ been. iden.tified as correlates to physical activity among youth. increasingly, physical activity among children s bemg acknowledged as a vital component of children's lives as it is a modifiable determinant of childh~d obesity. children's use of parks is mainly under the influence of parents; therefore, the purpose of this study was to assess parents' perspectives of city parks, using london ontario as a case study.m~~: this qualitative study targeted a heterogeneous sample of parents of children using local parks w thm london. parents with children using the parks were asked for minutes of their time and if willing, a s.hort interview was conducted. the interview guide asked parents for their opinion 'of city parks, particularly the one they were currently using. a sample size of parents is expected by the end of the summer.results: preliminary findings are identifying parents concern with the current jack of shade in local parks. most parents have identified this as a limitation of existing parks, and when asked what would make the parks better, parents agree that shade is vital. additionally, some parents are recognizing the v poster sessions focused discussions during the consultation: . women in _poverty . women with disability . immi· grant and racialized women . the built and _physica_l environment. . . . . r its· participants voiced the need for integration of the following issues withm the research and policy :::na; t) the intersectional nature of urban women's health i~sues wh~ch reflects the reality of women's complex lives ) the multisectional aspect of urban wo_m~n s health, ss~es, which reflects the diversity within women's lives ) the interse~roral _dynamics within _womens hves and urban health issues. these concepts span multiple sectors -mdudmg health, educat n, and economics -when leveraging community, research, and policy support, and engaging all levels of government.policy jmplicatiom: jn order to work towards health equity for women, plans for gender equity must be incorporated nationally and internationally within urban development initiatives: • reintroduce "women" and "gender" as distinct sectors for research, analysis, advocacy, and action. •integrate the multisectional, intersectional, and intersecroral aspects of women's lives within the framework of research and policy development, as well as in the development of action strategies. • develop a strategic framework to house the consultation priorities for future health research and policy development (for example, advocacy, relationship building, evidence-based policy-relevant research, priority initiatives}.note: research conducted by nnewh has been made possible through a financial contribution from health canada. the views expressed herein do not necessarily represent the views of health canada.p - (c) drugs, culture and disadvantaged populations leticia folgar and cecilia rado lntroducci n: a partir de un proyecto de reducci n de daiios en una comunidad urbana en situ· aci n de extrema vulnerahilidad surge la reflexion sobre el lugar prioritario de los elementos sociocuhurales en el acceso a los servicios de salud de diferentes colectivos urbanos. las "formas de hacer, pensar y sentir" orientan las acciones y delimitan las posibilidades que tienen los individuos de definir que algo es o no problema, asf como tambien los mecanismos de pedido de ayuda. el analisis permanenre del campo de "las culturas cotidianas" de los llamados "usuarios de drogas" aporta a la comprension de la complejidad del tema en sus escenarios reales, y colabora en los diseiios contextualizados de politicas y propuestas socio-sanitarias de intervenci n, tornandolas mas efectivas.mitodos: esta experiencia de investigaci n-acci n que utiliza el merodo emografico identifica elementos socio estructurales, patrones de consumo y profundiza en los elementos socio-simb icos que estructuran los discursos de los usuarios, caracterizandolos y diferenciandolos en tanto constitutivos de identidades socia les que condicionan la implementaci n del programas de reduccion de daiios.resultados: los resultados que presentaremos dan cuenta de las caracteristicas diferenciadas v relaciones particulares ~ntre los consumidores de drogas en este contexto espedfico. a partir de este e~tudio de caso se mtentara co ? enzar a responder preguntas que entendemos significativas a la hora de pensar intcrvcnciones a la med da de poblaciones que comparten ciertas caracteristicas socio-culturales. (cuales serian las .motivaciones para el cambio en estas comunidades?, cque elementos comunitarios nos ayudan a i:nnstnur dema~~a? • cque tenemos para aprender de las "soluciones" que ellos mismos encuenrran a los usos problemat cos? methods: our study was conducted by a team of two researchers at three different sites. the mapping consisted of filling in a chart of observable neighbourhood features such as graffiti, litter, and boarded housing, and the presence or absence of each feature was noted for each city block. qualitative observations were also recorded throughout the process. researchers analyzed the compiled quantitative and qualitative neighbourhood data and then analyzed the process of data collection itself.results: this study reveals the need for further research into the effects of physical environments on individual health and sense of well-being, and perception of investment in neighbourhoods. the process reveals that perceptions of health and safety are not easily quantified. we make specific recommendations about the mapping methodology including the importance of considering how factors such as researcher social location may impact the experience of neighbourhoods and how similar neighbourhood characteristics are experienced differently in various spaces. further, we discuss some of the practical considerations around the mapping exercise such as recording of findings, time of day, temperature, and researcher safety.conclusion: this study revealed the importance of exploring conceptions of health and well-being beyond basic physical wellness. it suggests the importance of considering one's environment and one's own perception of health, safety, and well-being in determining health. this conclusion suggests that attention needs to be paid to the connection between the workplace and the external environment it is situated in. the individual's workday experience does not start and stop at the front door of their workplace, but rather extends into the neighbourhood and environment around them. our procedural observations and recommendations will allow other researchers interested in the effect of urban environments on health to consider using this innovative methodology. introduction: responding ro protests against poor medical attention for sexually assaulted women and deplorable conviction rates for sex offenders, in the late s, the ontario government established what would become over hospital-based sexual assault care and treatment centres (sactcs) across the province. these centres, staffed around the clock with specially trained heath care providers, have become the centralized locations for the simultaneous health care treatment of and forensic evidence collection from sexually assaulted women for the purpose of facilitating positive social and legal outcomes. since the introduction of these centres, very little evaluative research has been conducted to determine the impact of this intervention. the purpose of our study was to investigate it from the perspectives of sexually assaulted women who have undergone forensic medical examinations at these centres.method: women were referred to our study by sactc coordinators across ontario. we developed an interview schedule composed of both closed and open-ended questions. twenty-two women were interviewed, face-to-face. these interviews were approximately one-to-two hours in length, and were transcribed verbatim. to date, have been analyzed for key themes.results: preliminary findings indicate that most women interviewed were canadian born ( 'yo), and ranged in age from to years. a substantial proportion self-identified as a visible minority ( 'x.). approximately half were single or never married ( %) and living with a spouse or family of origin ( %). most were either students or not employed ( %). two-thirds ( %) had completed high school and onethird ( %) was from a lower socio-economic stratum. almost two-fifths ( %) of women perceived the medical forensic examination as revictimizing citing, for example, the internal examination and having blood drawn. the other two-thirds ( %) indicated that it was an empowering experience, as it gave them a sense of control at a time when they described feeling otherwise powerless. most ( %) women stated that they had presented to a centre due to health care concerns and were very satisfied ( % ) with their experiences and interactions with staff. almost all ( %) women felt supported and understood.conclusions: this research has important implications for clinical practice and for appropriately addressing the needs of sexually assaulted women. what is apparent is that continued high-quality medical attention administered in the milieu of specialized hospital-based services is essential. at the same time, we would suggest that some forensic evidence collection procedures warrant reevaluation. the study will take an experiential, approach by chroruclmg the impa~ of the transition f m the streets to stabilization in a managed alcohol program through the techruque of narrative i~:uiry. in keeping with the shift in thinking in the mental health fie!~ ~his stu~y is based on a paradigm of recovery rather than one of pathology. the "inner views of part c pants hves as they portray their worlds, experiences and observations" will be presented (charm~z, , ~· ~)-"i?e p~ of the study is to: identify barriers to recovery. it will explore the exj?cnence of ~n~t zanon pnor to entry into the program; and following entry will: explore the meanmg ~nd defirutto~s of r~overy ~~d the impact of the new environment and highlight what supports were instrumental m movmg pan apants along the recovery paradigm.p -st (a) treating the "untreatable": the politics of public health in vancouver's inner city introdudion: this paper explores the everyday practices of therapeutic programs in the treadnent of hiv in vancouver's inner city. as anthropologists have shown elsewhere, therapeutic programs do not siinply treat physical ailments but they shape, regulate and manage social lives. in vancouver's inner city, there are few therapeutic options available for the treatment of -ilv. public health initiatives in the inner city have instead largely focused on prevention and harm reduction strategies such as needle exchange programs, safe injection sites, and safer-sex education. epidemiological reports suggest that less than a quarter of those living with hiv in the downtown eastside (dtes) are taking antiretroviral therapies raising critical questions regarding the therapeutic economy of antiretrovirals and rights to health care for the urban poor.methods: this paper is drawn from ethnographic fieldwork in vancouver's otes neighborhood focusing on therapeutic programs for hiv treatment among "hard-to-reach" populations. the research includes participant-observation at inner city health clinics specializing in the treatment of hiv; semi· structured interviews with hiv positive participants, health care professionals providing hiv treatment, and administraton working in the field of inner city public health; and, lastly, observation at public meetings and conferences surrounding hiv treatment.r.awlts: hiv prevention and treatment is a central concern in the lives of many residents living in the inner city -although it is just one of many health priorities afflicting the community. concerns about drug resistance, cost of antiretrovirals, and illicit drug use means that hiv therapy for most is characterized by the daily observation of their medicine ingestion at health clinics or pharmacies. daily observed treatment (dot) is increasingly being adopted as a strategy in the therapeutic management of "untreatable" populations. dot programs demand a particular type of subject -one who is "compliant" to the rules and regimes of public health. over emphasis on "risky practices," "chaotic lives," and "~dh~rence" preve~ts the public health system from meaningful engagement with the health of the marginalized who continue to suffer from multiple and serious health conditions and who continue to experience considerable disparities in health.~ the ~ffec~s of hiv in the inner city are compounded by poverty, laclc of safe and affordable houamg, vanous llegal underground economies increased rates of violence and outbreaks of ~~~·~ly tr~nsmitted infections, hepatitis, and tuberculosi: but this research suggests 'that public health uunauves aimed at reducing health disparities may be failing the most vulnerable and marginal of citiztl s. margaret malone ~ vi~lence that occurs in families and in intimate relationships is a significant urban, ~unity, and pu~hc health problem. it has major consequences and far-reaching effects for women, ~~--renho, you~ sen on, and families. violence also has significant effects for those who provide and ukllc w receive health care violence · · i · · . all lasses, · is a soc a act mvolvmg a senous abuse of power. it crosses : ' : ' ~ s;nden, ag~ ~ti~, cultures, sexualities, abilities, and religions. societal responseshali ra y oc:used on identificatton, crisis intervention and services for families and individuajs.promoten are only "-"--:-g to add h · ' · i in intimate relationshi with"-~"'.". ress t e issues of violence against women and vjoence lenga to consider i~ m families. in thi_s p~per, i analyze issues, propose strategies, and note c~· cannot be full -...l'-~ whork towards erad canng violence, while arguing that social justice and equity y -. ucvcu w en thett are people wh mnhod: critical social theory, an analysis that addresses culturally and ethnically diverse communities, together with a population health promotion perspective frame this analysis. social determinants of health are used to highlight the extent of the problem of violence and the social and health care costs.the ottawa charter is integrated to focus on strategies for developing personal skills, strengthening community action, creating supportive environments, devdoping healthy public policies, and re-orientating health and social services. attention is directed to approaches for working with individuals, families, groups, communities, populations, and society.ratdts: this analysis demonstrates that a comprehensive interdisciplinary, multisectoral, and multifaceted approach within an overall health promoting perspective helps to focus on the relevant issues, aitical analysis, and strategies required for action. it also illuminates a number of interacting, intersecting, and interconnecting factors related to violence. attention, which is often focused on individuals who are blamed for the problem of violence, is redirected to the expertise of non-health professionals and to community-based solutions. the challenge for health promoters working in the area of violence in families and in intimate relationships is to work to empower ourselves and the communities with whom we work to create health-promoting urban environments. social justice, equiry, and emancipatory possibilities are positioned in relation to recommendations for future community-based participatory research, pedagogical practices for health care practitioners, and policy development in relation to violence and urban health. the mid-main community health center, located in vancouver british columbia (bc), has a diverse patient base reflecting various cultures, languages, abilities, and socio-economic statuses. due to these differences, some mid-main patients experience greater digital divide barriers in accessing computers and reputable, government produced consumer health information (chi) websites, such as the bc healthguide and canadian health network. inequitable access is problematic because patient empowerment is the basis of many government produced chi websites. an internet terminal was introduced at mid-main in the summer of , as part of an action research project to attempt to bridge the digital divide and make government produced chi resources useful to a broad array of patients. multi-level interventions in co-operation with patients, with the clinic and eventually government ministries were envisioned to meet this goal. the idea of implementing multi-level interventions was adopted to counter the tendency in interactive design to implement a universal solution for the 'ideal' end-user [ ), which discounts diversity. to design and execute the interventions, various action-oriented and ethnographic methods were employed before and during the implementation of the internet terminal. upon the introduction of the internet terminal, participant observation and interviews were conducted using a motion capture software program to record a digital video and audio track of patients' internet sessions. this research provided insight into the spectrum of patients' capacities to use technology to fulfil their health information needs and become empowered. at the mid-main clinic it is noteworthy that the most significant intervention to enhance the usefulness of chi websites for patients appeared to be a human rather than a technological presence. as demonstrated in other ethnographic research of community internet access, technical support and capacity building is a significant component of empowerment ( ). the mid-main wired waiting room project indicates that medical practitioners, medical administrators, and human intermediaries remain integral to making chi websites useful to patients and their potential empowerment. ( ) over the past years the environmental yo~th alliance has been of~ering a.youth as~t. mappin~ program which trains young people in community research and evaluation. wh ~st the positive expenenc~ and relationships that have developed over this time attest to the success of this program, no evaluations has yet been undertaken to find out what works for t.he youth, what ~ould be changed, and what long term outcomes this approach offers for the youth, their local community, and urban governance. these topics will be shared and discussed to help other community disorganizing and uncials governments build better, youth-driven structures in the places they live.p - (a) the world trade center health registry: a unique resource for urban health researchers deborah walker, lorna thorpe, mark farfel, erin gregg, and robert brackbill introduction: the world trade center health registry (wfchr) was developed as a public health response to document and evaluate the long-term physical and mental health effects of the / disaster on a large, diverse population. over , people completed a wfchr enrollment baseline survey, creating the largest u.s. health registry. while studies have begun to characterize / bealth impacts, questions on long-term impacts remain that require additional studies involving carefully selected populations, long-term follow-up and appropriate physical exams and laboratory tests. wtchr provides an exposed population directory valuable for such studies with features that make ita unique resource: (a) a large diverse population of residents, school children/staff, people in lower man· hattan on / including occupants of damaged/destroyed buildings, and rescue/recovery/cleanup work· ers; (b) consent by % of enrollees to receive information about / -related health studies; (c) represenration of many groups not well-studied by other researchers; (c) email addresses of % of enrollees; (d) % of enrollees recruited from lists with denominator estimates; and (e) available com· parison data for nyc residents. wfchr strives to maintain up-to-date contact information for all enrollees, an interested pool of potential study participants. follow-up surveys are planned.methods: to promote the wtchr as a public health resource, guidelines for external researcher.; were developed and posted on (www.wtcregistry.org) which include a short application form, a twopage proposal and documentation of irb approval. proposals are limited to medical, public health, or other scientific research. researchers can request de-identified baseline data or have dohmh send information about their studies to selected wfchr enrollees via mail or email. applications are scored by the wtchr review committee, comprised of representatives from dohmh, the agency for toxic subst~nces and disease registry, and wtchr's scientific, community and labor advisory committees. a data file users manual will be available in early fall .~suits: three external applications have been approved in , including one &om a non-u.s. ~esearcher, all requesting information to be sent to selected wtchr enrollees. the one completed mail· mg~~ wtchr enrollee~ (o , wfc tower evacuees) generated a positive survey response rate. three additional researchers mtend to submit applications in . wfchr encourages collaborations between researchers and labor and community leaders.conclusion: studies involving wtchr enrollees will provide vital information about the long· term health consequences of / . wtchr-related research can inform communities, researcher.;, policy makers, health care providers and public health officials examining and reacting to and other disasters. t .,. dp'"f'osed: thi is presentation will discuss the findings of attitudes toward the repeat male client iden· ie as su e a and substance us'n p · · · · i · 'd . . - g. articipants will learn about some identified effective strategies or service prov ers to assist this group of i · f men are oft · d bl men. n emergency care settings, studies show that this group en viewe as pro emaric patient d i r for mental health p bl h h an are more ikely to be discharged without an assessmen !) ea rofr ems t. an or er, more cooperative patients (forster and wu · hickey er al., · r y resu ts om this study suggest th · · ' ' l · d tel' mining how best to h . d at negative amtudes towards patients, difficu nes e · as well pathways l_e_ p patientsblan ~ck of conrinuity of care influence pathways to mental health care. • uc\:ome pro emat c when p ti k · che system. m a ems present repeatedly and become "get stuc id methods: semi-structured intervie d . · (n= ), ed nurses (n= ) other ed ;s were con ucted with male ed patients (n= ), ed phys oans ' sta (n= ) and family physicians (n= ). patients also completed a poster sessions v diagnostic interview. interviews were tape-recorded, transcribed verbatim and managed using n . transcripts were coded using an iterative process and memos prepared capture emergent themes. ethics approval was obtained and all participants signed a detailed informed consent form.introduction: urban settings are particularly susceptible to the emergence and rapid spread of nt•w or rare diseases. the emergence of infectious diseases such as sars and increasing concerns over the next influenza pandemic has heightened interest in developing and using a surveillance systt·m which detects emerging public health problems early. syndromic surveillance systems, which use data b, scd on symptoms rather than disease, offer substantial potential for this by providing near-real-rime data which are linked to an automated warning system. in toronto, we are piloting syndromic data from the · emergency medical services (ems) database to examine how this information can be used on an ongoing basis for the early detection of syndromes including heat-related illness (hri), and influenza-like-illness (ill). this presentation will provide an outline of the planned desi_gn of this system and proposed evaluation. for one year, call codes which reflect heat-related illness or influenza-like-illness will be selected and searched for daily using software with a multifactorial algorithm. calls will he stratified by call code, extracted from the -ems database and transferred electronically to toronto public health. the data will be analyzed for clusters and aberrations from the expected with the realtime outbreak and disease surveillance (rods) system, a computer-based public health tool for the early detection of disease outbreaks. this -ems surveillance system will be assessed in terms of its specificity and sensitivity through comparisons with the well-established tracking systems already in place for hr! and ill. others sources of data including paramedic ambulance call reports of signs and . this study will introduce complementary data sources t~ the ed ch e~ complamt an~ o~~rthe-counter pharmacy sales syndromic surveillance data currently bemg evaluated m ~ther ontar~o cltles. . syndromic surveillance is a unique approach to proactive(~ dete~tmg early c.hangesm the health status of urban communities. the proposed study aims to provide evidence of differential effectiveness through investigating the use of -ems call data as a source of syndromic surveillance information for hr! and ili in toronto. introduction: there is strong evidence that primary care interventions, including screening, brief advi<:e, treatment referral and pharmacotherapy are effective in reducing morbidity and mortality caused by substance abuse. yet physicians are poor at intervening with substance users, in part because of lack of time, training and support. this study examines the hypothesis that shared care in addictions will result in decreased substance use and improved health status of patients, as well as increased use of primary care interventions by primary care practitioners (pcps). methods: the addiction medicine service (ams) at st. joseph's health centre's family medicine department is in the process of being transformed from its current structure as a traditional consult service into a shared care model called addiction shared care (asc). the program will have three components: education, office systems and clinical shared care. as opposed to a traditional consult service, the patient will be booked with both a primary care liaison worker (pcl) and addictions physician. patients referred from community physicians, the emergency department and inpatient medical and psychiatric wards will be recruited for the study as well as pcps from the surrounding community. the target sample size is - physicians and a similar number of patients. after initial consult, patient will be recruited into the study with their consent. the shared-case model underlines the interaction and collaboration with the patient's main pcp. asc will provide them with telephone consults, advice, support and re-assessment for their patients, as well as educational sessions and materials such as newsletters and informational kits.results: the impact of this transition on our patient care and on pcp's satisfaction with the asc model is currently being evaluated through a grant provided by the ministry of health & long term care. a retrospective chart review will be conducted using information on the patient's substance use, er/clinic visits, and their health/mood status. pcp satisfaction with the program will be measured through surveys and focus groups. our cost-effectiveness analysis will calculate the overall cost of the program per patient..conclusion: this low-cost service holds promise to serve as an optimal model and strategy to improve outcomes and reduce health care utilization in addict patients. the inner city public health project introduction the inner city public health project (icphp) was desi.gned to explore new an~ innovative ways to reach marginalized inner city populations that par-t c pate m high health-nsk beha~ ors. much of this population struggles with poverty, addictions, mental illness and homelessness, creatmg barriers to accessing health services and receiving follow-up. this pro ect was de~igned to evaluat~ .~e success of offering clinics in the community for testing and followup of communicable diseases uuhzmg an aboriginal outreach worker to build relationships with individuals and agencies. v n(demographics~ history ~f testi~g ~nd immunization and participation in various health-risk behaviors), records of tesnng and mmumzat ons, and mterviews with partner agency and project staff after one year.. results: t~e chr ~as i~strumental in building relationships with individuals and partner agencies ' .° the c~mmun_ ~ re_sultmg m req~ests for on-site outreach clinics from many of the agencies. the increase m parnc pat n, the chr mvolvement in the community, and the positive feedback from the agen? staff de~onstrated that.the project was successfully creating partnerships and becoming increasingly integrated m the community. data collected from clients at the initial visit indicated that the project was reaching its target populations and highlighted the unique health needs of clients, the large unmet need for health services and the barriers that exist to accessing those services. ~usion: the outreach clinics were successful at providing services to target populations of high health-nsk groups and had great support from the community agencies. the role of the chr was critical to the success of the project and proved the value of this category of health care worker in an urban aboriginal population. the unmet health needs of this disadvantaged population support the need for more dedicated resources with an emphasis on reducing access barriers. building a caring community old strathcona's whyte avenue, a district in edmonton, brought concern about increases in the population of panhandlers, street people and homeless persons to the attention of all levels of government. the issue was not only the problems of homelessness and related issues, but feelings of insecurity and disempowerment by the neighbourhood residents and businesses. their concerns were acknowledged, and civic support was offered, but it was up to the community itself to solve the problem. within a year of those meetings, an adult outreach worker program was created. the outreach worker, meets people in their own environments, including river valley camps. she provides wrap-around services rooted in harm reduction and health promotion principles. her relationship-based practice establishes the trust for helping clients with appropriate housing, physical and/or mental health issues, who have little or no income and family support to transition from homelessness. the program is an excellent example of collaboration that has been established with the businesses, community residents, community associations, churches, municiple services, and inner-city agencies such as boyle street community services. statistics are tracked using the canadian outcomes research institute homes database, and feedback from participants, including people who are street involved. this includes an annual general meeting for community and people who are homeless. the program's holistic approach to serving the homeless population has been integral, both in creating community awareness and equipping residents and businesses to effectively interact with people who are homeless. through this community development work, the outreach worker engages old strathcona in meeting the financial and material needs of the marginalized community. the success of this program has been surprising -the fact is that homeless people's lives are being changed; one person at a time and the community has been changed in how they view and treat those without homes. over two years, the program has successfully connected with approximately seventy-five individuals who call old strathcona home, but are homeless. thirty-six individuals are now in homes, while numerous others have been assisted in obtaining a healthier and safer lifestyles by becoming connected with other social/health agencies. the program highlights the roots of homelessness, barriers to change and requirements for success. it has been a thriving program and a model that works by showing how a caring community has rallied together to achieve prosperous outcomes. the spn has created models of tb service delivery to be used m part~ers~ p with phannaceunca compa-. · · -. t' ns cooperatives and health maintenance orgamzanons (hmos). for example, the mes, c v c orgamza , . · b tb d' · spn has established a system with pharmaceutical companies that help patients to uy me cmes at a special discounted rate. this scheme also allows patients to get a free one-_month's worth of~ dru_g supply if they purchase the first months of their regimen. the sy_s~e~s were ~es gned to be cm~pattble with existing policies for recording and documentation of the ph hppme national tuberculosis program (ntp). aside from that, stakeholders were also encouraged to be dots-enabled through the use of m~nual~ and on-line training courses. the spn initiative offers an alternative in easing the burden of tb sc:rv ce delivery from rhe public sector through the harnessing of existing private-sector (dsos). the learnmgs from the spn experience would benefit groups from other locales that _work no~ only on ~ but other health concerns as well. the spn experience showcases how well-coordinated private sector involvements help promote social justice in health delivery in urban communities.p - (c) young people in control; doing it safe. the safe sex comedy juan walter and pepijn v. empelen introduction: high prevalence of chlamydia and gonorrhoea have been reported among migrants youth in amsterdam, originating from the dutch antilles, suriname and sub-sahara africa. in addition, these groups also have high rates of teenage-pregnancy (stuart, ) and abortions (rademakers ), indicating unsafe sexual behaviour of these young people. young people (aged - ) from the so· called urban scene (young trendsetters in r&b/hip hop music and lifestyle) in amsterdam have been approached by the municipal health service (mhs) to collaborate on a safe sex project. their input was to use comedy as vehicle to get the message a cross. for the mhs this collaboration was a valuable opportunity to reach a hard-to-reach group.mdhods: first we conducted a need assessment by means of a online survey to assess basic knowledge and to similtaneously examine issues of interest concerning sex, sexuality, safer sex and the opposite sex. second, a small literature study was conducted about elements and essential conditions for succesful entertainment & education (e&e) (bouman ), with as most important condition to ensure that the message is realistic (buckingham & bragg, ) . third a program plan was developed aiming at enhancing the stl/hiv and sexuality knowledge of the young people and addressing communication and educational skills, by means of drama. subsequently a safe sex comedy show was developed, with as main topics: being in love, sexuality, empowerment, stigma, sti, hivand safer sex. the messages where carried by a mix of video presentation, stand up comedy, spoken word, rap and dance.results: there have been two safe sex comedy shows. the attendance was good; the group was divers' with an age range between and year, with the majority being younger than year. more women than men attended the show. the story lines were considered realistic and most of the audients recognised the situations displayed. eighty percent of the audients found the show entertaining and % found it edm:arional. from this %, one third considers the information as new. almost all respondents pointed our that they would promote this show to their friends.con.clusion: the s.h<_>w reached the hard-to-reach group of young people out of the urban scene and was cons d_ered entert~mmg, educational and realistic. in addition, the program was able in addressing important issues, and impacted on the percieved personal risk of acquiring an sti when not using condoms, as well as on basic knowledge about stl's. introduction: modernity has contributed mightily to the marginality of adults who live with mental illnesses and the subsequent denial of opportunities to them. limited access to social, vocational, educational, and residential opportunities exacerbates their disenfranchisement, strengthening the stigma that has been associated with mental illness in western society, and resulting in the denial of their basic human rights and their exclusion from active participation in civil society. the clubhouse approach tn recovery has led to the reduction of both marginality and stigma in every locale in which it has been implemented judiciously. its elucidation via the prism of social justice principles will lead to a deeper appreciation of its efficacy and relevance to an array of settings. methods: a review of the literature on social justice and mental health was conducted to determine core principles and relationships between the concepts. in particular, fondacaro and weinberg's ( ) conceptualization of social justice in community psychology suggests the desirability of the clubhouse approach in community mental health practice. a review of clubhouse philosophy and practice has led to the inescapable conclusion that there is a strong connection between clubhouse philosophy-which represents a unique approach co recovery--and social justice principles. placing this highly effective model of community mental health practice within the context of these principles is long overdue. via textual analysis, we will glean the principles of social justice inherent in the rich trove of clubhouse literature, particularly the international standards of clubhouse development.results: fondacarao and weinberg highlight three primary social justice themes within their community psychology framework: prevention and health promotion; empowerment, and a critical pnsp<"<·tive. utilizing the prescriptive principles that inform every detail of clubhouse development and th<" movement toward recovery for individuals at a fully-realized clubhouse, this presentation asserts that both clubhouse philosophy and practice embody these social justice themes, promote human rights, and empower clubhouse members, individuals who live with mental illnesses, to achieve a level of wdl-heing and productivity previously unimagined.conclusion: a social justice framework is critical to and enhances an understanding of the clubhouse model. this model creates inclusive communities that lead to opportunities for full partic pil!ion civil society of a previously marginalized group. the implication is that clubhouses that an· based on the international standards for clubhouse programs offer an effective intervention strategy to guarantee the human rights of a sizable, worthy, and earnest group of citizens. to a drastic increase in school enrollment from . million in to . million in .s. however, while gross enrollment rates increased to °/., in the whole country after the introduction of fpe, it remained conspicuously low at % in the capital city, nairobi. nairobi city's enrollment rate is lower .than thatof all regions in the country except the nomadic north-eastern province. !h.e.d sadvantage of children bas_ed in the capital city was also noted in uganda after the introduction of fpe m the late s_-many_ education experts in kenya attribute the city's poor performance to the high propornon of children hvmg m slums, which are grossly underserved as far as social services are concerned. this paper ~xammes the impact of fpe and explores reasons for poor enrollment in informal settlements m na rob city. methods: the study utilizes quantitative and qualitative schooling data from the longitudinal health and demographic study being implemented by the african population and health research center in two informal settlements in nairobi. descriptive statistics are used to depict trends in enrollment rates for children aged - years in slum settlements for the period - . results: the results show that school enrollment has surprisingly steadily declined for children aged - while it increased marginally for those aged - . the number of new enrollments (among those aged years) did not change much between and while it declined consistently among those aged - since . these results show that the underlying reasons for poor school attendance in poverty-stricken populations go far beyond the lack of school fees. indeed, the results show that lack of finances (for uniform, transportation, and scholastic materials) has continued to be a key barrier to schooling for many children in slums. furthermore, slum children have not benefited from fpe because they mostly attend informal schools since they do not have access to government schools where the policy is being implemented.conclusion: the results show the need for equity considerations in the design and implementation of the fpe program in kenya. without paying particular attention to the schooling needs of the urban poor children, the millennium development goal aimed at achieving universal primary education will remain but a pipe dream for the rapidly increasing number of children living in poor urban neighborhoods.ps- (c) programing for hiv/aids in the urban workplace: issues and insights joseph kamoga hiv/aids has had a major effect on the workforce. according to !lo million persons who are engaged in some form of production are affectefd by hiv/aids. the working class mises out on programs that take place in communities, yet in a number of jobs, there are high risks to hiv infection. working persons sopend much of their active life time in workplaces and that is where they start getting involved in risky behaviour putting entire families at risk. and when they are infected with hiv, working people face high levels of seclusion, stigmatisation and some miss out on benefits especially in countries where there are no strong workplace programs. adressing hiv/aids in the workplace is key for sucessfull responses. this paper presents a case for workplace programing; the needs, issues and recommendations especially for urban places in developing countries where the private sector workers face major challenges. key: cord- -c km w authors: mindell, jennifer s.; ergler, christina; hopkins, debbie; mandic, sandra title: taking the bus? barriers and facilitators for adolescent use of public buses to school date: - - journal: travel behav soc doi: . /j.tbs. . . sha: doc_id: cord_uid: c km w transport to school can contribute significantly to adolescents’ physical activity but in new zealand – as in many other countries around the world – many adolescents are driven to school. public transport offers an opportunity to integrate incidental active transport into school commutes. in this paper, we bring together multiple sources of data into a multi-method study to elucidate the barriers to and facilitators of public transport use by adolescents for school travel in dunedin, new zealand, a city with low rates of public transport use. the data include a public bus survey from otago school students lifestyle survey (ossls, adolescents); the built environment active transport to school (beats) study parental survey ( parents), focus groups ( adolescents, parents, teachers) and semi-structured interviews ( principals); interviews with three policy-makers from local/regional/national agencies; and analysis of relevant local/regional/national strategies/transport plans. the findings show how distance to school, cost, parental trip chaining, built environment features, the weather, convenience, and safety perceptions are major barriers to using public transport to school. moreover, current transport planning documents do not favour public health. a number of recommendations that could increase public transport use are made including: raising parking prices to discourage parents driving and trip-chaining; improving bus infrastructure and services; providing subsidies; and changing perceptions of public transport use and users. these actions, however, require collaboration between government authorities across the local, regional and national scale. travel can provide access to employment and education, as well as opportunities for physical activity and social engagement (mindell et al., ) . how people travel affects both their own health and that of others (cohen et al., ) . many factors affect travel mode choice, including perceptions of transport modes (e.g. perceptions of public transport in car-dominated societies (murray et al., ) ); political frameworks and environment; funding regimes; and the built and natural environment. new zealand's transport system is characterised by high private vehicle ownership and use ; limited availability and utilisation of public transport; and low rates of active transport (shaw and russell, ) . at the same time, new zealand had the third highest adult obesity prevalence among oecd countries in , while % of - year olds were overweight or obese in (ministry of health, . physical activity levels in new zealand children and adolescents are inadequate (smith et al., a,b) with just under % of those aged - years meeting minimum physical activity guidelines (≥ minutes of moderate to vigorous physical activity (mvpa) every day) (kek et al., ; smith et al., a) . given reported reductions in physical activity (aubert et al., ) and rises in obesity at all ages in most high income countries, the opportunity to use active travel (primarily walking and/or cycling) to incorporate physical activity into everyday life is particularly important. the use of public transport is often associated with 'active travel', with opportunities for increased physical activity to and from bus, tram and train stations (bartels et al., ; besser and dannenberg, ; durand et al., ; jones et al., ; lachapelle and pinto, ; rissel et al., ) . public transport, which has a range of potential benefits for the health of the planet and of people, offers the opportunity to access educational, health and social sites while still incorporating a degree of physical activity and independence. this is important, because rates of active travel to school have fallen in new zealand over the past several decades (ministry of transport, ) , similar to many high- (gray et al., ) and middle-income countries (de sá et al., ) . in - , only % of new zealand adolescents regularly cycled and % walked to school (ministry of transport, ) . this is mirrored by new zealand adolescents' ongoing preference for carbased travel (hopkins et al., ) and substantially less independent mobility for schoolchildren compared with earlier generations (bhosale et al., ; ergler, ; porskamp et al., ) . barriers to active travel to school by new zealand adolescents include home-to-school distance, time constraints, after-school activities, lack of social support, the convenience of being driven to school, the weather, environmental factors such as lack of cycle parking or cycle paths, lack of interest, and both adolescents' and parents' concerns regarding traffic safety and absence of school zoning (hopkins and mandic, ; ikeda et al., ; kearns et al., ; mandic et al., a mandic et al., ,b, . little is known about the factors which enable and constrain the use of public buses for school travel, unlike the myriad of studies of walking or door-to-door school buses (hinckson, ; howley, ; park and kim, ; wilson et al., ) or public bus use in general (barker et al., ; broome et al., ; moore, ; simons et al., ) . distance is important, as is the bus service and quality including frequency, journey time and connections (wilson et al., ; hinckson, ; broome et al., ) . safety associated with crowdedness and lack of seatbelts contribute to the negative perception of bus use (hinckson, ) . nonetheless, adolescents reported enjoying the time to socialise on buses (hinckson, ; jones et al., ; green et al., ) , but bullying and the costs of buses were seen as barriers (barker et al., ; broome et al., ; hinckson, ) . in contrast, free public bus schemes can be physically and socially enriching experiences for young people jones et al., ) . the research presented in this paper therefore aimed first to elucidate the specific barriers to and facilitators of public transport use by adolescents for school travel in a city with low rates of public transport use for this purpose. these data were complemented by analysis of relevant national, regional and local transport policy documents and interviews with policy-makers, to help identify potential strategies to increase public bus use. the city of dunedin (population c. , ) is located on the east coast of the south island of aotearoa new zealand. dunedin is a coastal city with a territorial land area of , . km and city-proper of km . built on the mouth of a km long natural harbour, dunedin has a relatively flat central business district (cbd), and hilly surrounding suburbs. much residential housing is situated on the hills, requiring navigating often multiple hills and large distances to travel to school and work. dunedin's transport system is therefore highly dependent on private car transport. a bus network provides dunedin's public transport system; this was used for only % of all trips in - (early et al., ) . it has been reported that the bus network does not meet the expectations of users due to its low frequency and route system (early et al., ) . regarding using the bus network for school travel, fewer than half of dunedin's adolescents enrol in the closest school , resulting in an increasing distance to school, reduced rates of active transport to/from school, and increased reliance on motorised transport, mainly by private vehicles keall et al., ) . this paper reports on multiple data sources (fig. ) which engaged with a variety of stakeholders on the question of public bus use by secondary school students. the specific research questions and the data sources used to address these are provided in table . each of the data sources and relevant research methods are described briefly below and summarised in table . the otago school students lifestyle survey (ossls), conducted in the otago region of new zealand in , included adolescents from ten of twelve dunedin secondary schools (mandic et al., ) . all participants signed consent prior to participation. for students under the age of years, parents had the option to sign parental opt-out forms if they did not want their child to participate. the questionnaire package included questions on demographics, school travel, lifestyle habits and sport participation (mandic et al., ) as well as public bus service (including open-ended comments) and youth space preferences. the questions relating to demographics, travel to school and public bus use in dunedin were analysed using descriptive statistics. findings (including comments from open-ended questions about the public bus service in dunedin) were summarised and presented as a technical report for the dunedin city council (dcc) and the otago regional council (orc) (mandic and skidmore, ) . original research data from that study were analysed for this paper. all dunedin secondary schools participated in the beats study, which was conducted in dunedin, new zealand - (mandic et al., ) . the overall study included surveys of secondary school students and their parents, focus groups with students, parents and teachers and semi-structured interviews with school principals (fig. , table ) as well as assessment of the built environment characteristics of the home and school neighbourhoods. participants signed written consent prior to participation. for students under the age of , parents signed either opt-in or opt-out consent, based on the school's preference. data from the bus to school section of the beats parental survey completed by parents (one parent per household) were used to analyse parents' perspectives on dunedin adolescents' use of public buses to school (table ) . beats focus groups and interviews were designed and conducted by dh with another research staff member present. discussions covered a wide range of topics including but not limited to the norms, experiences and perceptions of different transport modes such as public transport (mandic et al., ; sandretto et al., ) . all sessions were recorded and subsequently transcribed. lc (see credit statement) developed a coding framework and coded all transcripts of the interviews with adolescents, parents, teachers and principals, with a particular focus on participants' perspectives on facilitators and barriers to bus transport to school. the initial codes were regularly discussed and checked by ce and then developed into themes (braun and clarke, ) . the qualitative interviews along with the open-ended comments in the adolescents' bus survey provided insights into the complexities of why using a bus to school seems to be less appealing than other modes of transport for many people. an overview of the themes and sub-themes developed is provided in table . four main themes were created: . transport mode; . perceptions, knowledge and experience; . climate and weather; and . school travel responsibilities. three national, three regional and four local/city level policy documents published between and september (table ) were chosen to gain insights into the land transport hierarchy of new zealand and how public transport is planned for different levels. these ten documents were selected based on their relevance to transport to school both in the national and local context and ranged from legally binding documents to strategic documents and plans. all documents were publicly available, downloaded from the official government websites and then coded thematically and assessed as to whether they: discussed transport to school; considered public health from a transport perspective; approached public health from a physical activity point of view; and/or placed any emphasis on transport diversity. the policy analysis informed the development of the interview schedule with policy-makers to gain, for example, a better understanding of existing and planned integration initiatives and roadblocks for a move towards a more intgrated, multi-modal transport system (section . . ). interviews were undertaken with three policy-makers working in dunedin, to provide further insight on public transport issues raised by the adolescents, parents, teachers and principals and on policy issues that emerged as a result of the policy analysis such as planned and desirable initiative for enticing public transport in light of known usage barriers. interviews were conducted with one person from each of the new zealand transport agency (nzta), orc, and dcc. these three agencies -directly and indirectly -shape and implement policy directives into the dunedin transport system and thus can provide institutional insights. individuals were selected based on their knowledge and involvement in shaping and oversights of dunedin's transport system at the local, regional and national level. participants were invited by email and they signed written consent prior to participation. these interviews, designed and conducted by lc (see credit statement), focused on barriers and enablers for adolescents using public transport to school; issues for developing an effective public transport policy to school; the role of policy for increasing public transport use; and general issues of the current transport system. the interviews were digitally recorded, transcribed, coded and analysed thematically by lc with input from ce. three themes were developed from interviews with policy-makers relating to: barriers and enablers for using public transport; issues of the current transport system and for developing an effective transport policy; and the role of policy for increasing public transport use (table ). this paper brings the four methods and datasets described above into conversation using a multi-method approach. multi-method approaches differ from mixed methods, as they may not be designed with multiple methods in mind, and thus the 'mixing' of the different data sets is not pre-planned, but rather occurs after all of the data sets have been independently collected and analysed. this approach overcomes the inherent weaknesses and limitations from the different methods independently, and deliberately combines a diversity of methods within one investigation (brewer and hunter, ). yet like some forms of mixed methods, the different methods are "practiced in parallel… [weaving] together diverse research techniques to fill gaps, add context, envision multiple truths, play different sources of data off each other, and provide a sense of both the general and the particular" (cope and elwood, : p ) . this relates to a pragmatist philosophical stance which focuses on 'what works' for a particular topic, question or concern (rossman and wilson, ) . in the present investigation, our use of multiple methods allowed us to engage with wider sets of actor groups, perspectives and understandings around bus use in the case study city, dunedin. none of the methods or data sets, and thus no participant groups, were prioritised, but all were viewed as equally important for helping us to understand bus use. in doing so we shed light on the diversity and complexity of needs and experiences and thus provide richer strategies to increase public bus use than a single method or dataset is able to do. the data were collected at different times over an -year period ( - ) , therefore they were collected sequentially. the different methods were brought together to help the authors understand the barriers to and facilitators of adolescent use of public buses for school transport in a comprehensive and detailed way and to formulate relevant policy suggestions and strategies. research ethics approval was obtained for each of these studies from the university of otago ethics committee (reference numbers: / (beats); / (ossls); d / (policy-maker interviews)). in , students ( % boys; age: . ± . years; % school years - , % school years - ; % new zealand european) from ten dunedin secondary schools completed young people's bus survey as part of the otago school students lifestyle j.s. mindell, et al. travel behaviour and society ( ) - survey (ossls). overall, % of dunedin secondary school students used public buses, with no significant difference between school years. in the total sample, the most common locations that students travelled to by bus were school ( %), shops in the town/city centre ( %) and other shops ( %) and recreational facilities ( %). among public bus users, % used the bus to get to school on a daily basis, % nearly every day, % once or twice per week and % never or hardly ever. less than % of public bus users reported daily or nearly daily use of public bus to all other locations. overall, % of students usually travelled on the bus with friend(s), % travelled alone, % with a sibling, % with a parent or other adult, and % with other(s). among students who used public bus, % liked travelling by bus. the most frequently reported reasons why students liked travelling by bus included: getting to a desired location ( %); socialising with friends on the bus ( %); the bus being warmer and drier than walking or cycling ( %); independence ( %); taking a bus being easier than walking or cycling ( %); and no need to look for a car park ( %). students also perceived bus drivers as friendly ( %) and buses as an environmentally friendly way to travel ( %) and safer than cycling ( %). the most frequently reported barriers to public bus use among adolescents were cost, being driven around by parents, travelling long distances, infrequent and slow bus service, unsuitable bus timetable and lack of knowledge of the bus timetable (table ). compared with bus users, a greater proportion of students who were not using public bus reported barriers associated with the public bus cost, waiting or getting to the bus stop, lack of company for riding on the bus and lack of knowledge of the bus timetable (table ). non-bus users also reported higher rates of being driven around by parents and of car ownership and were less concerned with the bus frequency and timetables compared with bus users. parents (n = ; parent age . ± . years; % females) of secondary school students (student age . ± . years; % girls) from all dunedin secondary schools completed the beats parental survey (mandic et al., b) . overall, % of students used motorised transport to school, % used active transport and % used mixed modes. nine percent of parents reported that their adolescent children travel to school using public bus. the average distance to school was . ± . km (median: . km; iqr: . km to . km), with no significant difference between parents whose adolescents travelled to school by bus and those whose adolescents who did not. overall, % of parents reported having both public and school bus service available near their home, % had public bus only, % had school bus only, % had no public or school bus service and % were unsure. the most frequently reported parental barriers to public bus use were adolescents' extracurricular activities; perceived convenience of car trip chaining; and the cost of public buses (table . ). perceptions of convenience of car trip chaining and living too close to school or too far from a bus stop were significantly different between parents whose adolescents travelled to school by public bus compared with their counterparts who did not. the qualitative insights from parents and adolescents showed the importance of private motorised transport, particularly as this related to perceived convenience, and cost. convenient travel was interpreted as "quick" and/or "easy" transport options, which in turn makes public transport a less appealing transport mode. for example, one adolescent stated that "i like to be able to be flexible with my travelling times because there is too much pressure to catch the bus at the right time when i can just table use of data sources to address specific research questions. how much are public buses used by adolescents for travel to/from school? √ what aspects should be considered by policy-makers when developing a public transport to school policy for adolescents? what policies are likely to increase use of public buses for school travel? mindell, et al. travel behaviour and society ( ) - drive myself and not have to worry" [source: bus survey]. in turn, this means that public bus transport becomes synonymous with a slower speed, less reliability and lower frequency than alternatives -such as the private car. thus, perceptions of bus transport occur in direct relation to other transport modes, and are interpreted through the lens of the dominant car-based transport system. for instance, participants reflected on the perceived 'time savings' accrued from being driven to school (by parents, caregivers, friends), which were interpreted in relation to time which may be spent waiting for and travel on buses. dunedin adolescents habitually use private vehicles for both school and general travel purposes. this was coupled with parental practices, and perceived convenience to drop their children at school en-route to or from work, even when this means their offspring has to arrive much earlier than required. for example, a parent stated that: "i think it's just whatever fits in with the parents, whatever makes it easier for the parents… some children that i know of are being dropped off at school at like : " [parental focus group ]. trip chaining is perceived as normal, appropriate and convenient within the busy family life. families highlight the extra financial costs associated with bus travel when the car is taken out already: "if you're driving into work then it will cost you more to put your kids on a bus, it's cheaper just to drop them off" [parental focus group ]. this was reiterated by students, who noted that the bus "needs to be cheaper" and that "it costs way too much just for one zone" [bus survey]. while for some students their place of residence dictated their choice of transport, others revealed that they had little input in the decision making on their mobilities. for some, the distance to their school was simply "too far" to use public transport, with participants stating that: "service is out of reach to some places i need to go" [bus survey]. others did not have parental permission to use public transport or sought to avoid potential disagreements with their parents or family members. moreover, many participants feared being late for school or other activities, with the potential for negative repercussions deterring them from using the bus: "sometimes the buses are late and i might miss out on an important event or school" [bus survey]. school principals also highlighted that their pupils either arrive early or are late as public bus schedules are not in synchronicity with the school day (see table ). participation in extracurricular activities also reinforces the use of private vehicles, with students stating: "i am so busy and i have so many activities to go to so i don't really go on the bus" [bus survey]. it was not only the unreliability of the bus schedule, but also the infrequent running times of buses that create problems for adolescents as "[t]ime . the low uptake of bus use is also linked to students' lack of knowledge of how to use dunedin buses, their unfamiliarity with the different routes, and managing the timetables. therefore, it is not j.s. mindell, et al. travel behaviour and society ( ) - surprising that many students voiced their concerns of selecting the right bus for their needs, or missing their required stop and consequently alighting in an unfamiliar environment. as a result, the bus was identified as a last resort -an option if all else failed. this means that students are travelling by bus at a time of stress and/or pressure, thus intensifying the experiences of uncertainty and time constraint. adolescents identified the bus, and those who travelled by bus, in terms of the 'loser cruiser', which may underpin a concern of using this mode, and of being associated with regular bus clients. this was articulated by a bus survey participant who said that buses "smell, [are] filled with weirdos and strange people who can't afford a car". however, some students developed coping strategies to make their experience on the bus more pleasant, and quicker, for instance by taking an earlier, less crowded bus. a student focus group participant stated that "there is a difference between catching the : bus and the : bus. the : bus will get you here about : - : , whereas the : bus will get you here at like : ; because it's stopping and starting. it gets busier and it takes so long, which is why i prefer going early" [student, focus group ]. among the ten analysed policy documents, six explicitly discussed transport to school (# , # , # , # , # , # , table ); two considered public health from a transport perspective (# , # ); and one approached public health from a physical activity perspective (# ) (copland, ) . four documents placed an emphasis on transport diversity: providing for both young, physically active people and elderly or mobility-impaired transport-disadvantaged people (# , # , # , # ). car dependence and the ways it manifests as an issue at different scales was mentioned in several local documents but few documents explicitly discussed how car dependence can be addressed. one document (# ) identified greater use of public transport to school by adolescents as a desirable goal. yet public health was neither prioritised nor legislated for in transport planning in new zealand at that time, which focused then on growth and viability. dunedin appeared as an exception, as strategic planning documents (e.g. # ) refereed to the intersections between transport and public health. three themes emerged from analysing interviews with policy-makers, relating to: barriers and enablers for using public transport; issues of the current transport system and for developing an effective transport policy; and the role of policy for increasing public transport use (table ) . policy-makers noted the roles of pricing strategies and the cost of using public transport as a potential barrier to bus uptake, and this is understood in relation to -or competition with -other modes such as private car. as the capital and annual fixed costs of car ownership are often not directly considered by private vehicle drivers on a day-to-day basis, the cost of bus transport needs to compete with the daily marginal costs of driving, such as parking and petrol. a dcc participant reflected upon this, noting how "it's actually very expensive to own a car, but people don't perceive it to be that way. you've got to keep it on the road, and gas, and tyres and all that sort of thing". the pricing structure of bus transport was also seen in relation to wider transport policies. for instance, in queenstown, a town in the otago region, new zealand, for which the orc also plays a role in transport planning, parking revenue directly supports subsidising the bus system, thus allowing lower prices for the public bus compared with other places in the country, such as dunedin. an orc participant noted that "if we did something similar with the dunedin city council and their parking revenue, we could introduce more competitive fares", both suggesting a possibility for reducing the cost of bus transport, but also understanding the connections between private and public transport at the policy level. a change in policy through "…car-parking charges or road pricing might get the parents to change their behaviour" [dcc respondent] . the public buses are often used by students to travel to school, yet these operate separately -with different management and pricing structures -from school buses. while traditionally students used dedicated school buses, participants noted how changes in the national policy was increasing the number of students using public buses, which means that "[transport to school is] becoming more a part of our remit as a council" (orc respondent) and thus, "[the orc] have made a decision in their regional public transport plan that there isn't really a need to fund separate school services for kids, they can use the new (public) network". this raises questions about the suitability of their network for school transport, the public/student mix, but also funding the public network table qualitative analysis of the interviews with policy-makers. barriers and enablers to use public transport to school cost of bus service ( ) safety ( ) providing for the transport disadvantaged ( ) travel practices ( ) time and convenience ( ) issues of the current system and for developing an effective transport policy collaboration ( ) providing for the transport disadvantaged ( ) planning documents ( ) public bus compared to school bus ( ) role of policy for increasing public transport use transport policies ( ) future planning ( ) j.s. mindell, et al. travel behaviour and society ( ) - and the complex entanglement of and less than streamlined involvement of different agencies in providing bus services. one participant argued: "i think one of the areas you would conjure with is the division of responsibility between the ministry of education providing buses to school, and the public bus system (run by the orc) to support kids to school, there is sort of two views aren't there? i.e. we don't want children polluting our normal [public] buses, but equally, i personally think that they could be a very useful sort of revenue to support the public bus service" [dcc respondent] it was clear that dunedin policy-makers thought that health is about healthcare and treating illness, rather than about maintaining good mental and physical health. the decisions made by the local and regional councils do not relate to public health objectives but are focused on accessibility and safety, with one participant noting that "i think traditionally public health hasn't had a lot of influence on decision-making. … most of my professional career we've been very focused on doing no harm, so safety's been really important, so that's driven down kids walking and cycling to school" [dcc respondent] . at the regional scale this point was also made, with a participant noting how: "[the link between physical activity and public transport is] not [emphasised in the otago regional public transport plan], i mean i don't really know how we would incorporate it, because the plan is the five most common 'other' responses included unfriendly bus drivers, distrust of other passengers and fears for safety, fears of getting on the wrong bus or off at the wrong stop, and receiving no help from bus drivers, parents that do not trust the service, or other people, and would not let their children use it, and dislike of sitting next to unfriendly unfamiliar people. barriers to public bus use in dunedin as reported by parents of secondary school students. sort of a 'cover all' type policy, and yeah we just have a lot of elderly and disabled, so it's like trying to provide for two polar opposites" [orc respondent] changes to young people's behaviours and practices, particularly at the intersection of technological innovation were identified as potential opportunities for incentivising bus travel. for instance, a participant from the nzta noted: "you don't want kids waiting for ages for a bus at a bus stop because there's a perceived danger that people have. so, with technology, it can be 'just in time' type stuff, so that kids can get to the stop, the services are there and they can see where the bus is." this can mean that the perceived safety of bus transport increases. as well as safety benefits, real-time information on smart devices was thought to make bus transport more appealing by offering accurate information on-the-go, an nzta participant argued "anything on a smartphone is definitely more attractive to teenagers" [orc respondent]. such real-time information could reduce uncertainty; reduce waiting times by facilitating users' appropriate arrival times at the bus stop; make bus use easier; and be an efficient method for easy payment. such technologies also have the potential to offer better integration between modes, so that bus transport is no longer seen in isolation from other modes, such as active modes (walking, cycling) but also connectivity between types of public transport, taxi-hubs and more. an nzta participant noted how "a key role for us is working towards really good integrated transport solutions as part of a whole system. so we are much more into the system thinking now… you can't just think of it as once they [students] are on the bus they are done with […] so we've got to look at opportunities for people to maybe get off the bus and jump on the bike to get home, and then you know, it's just making the whole thing more convenient and just giving more opportunities and choice really". most adolescents in dunedin did not travel to school by bus. this trend differs from cities such as vienna where most high school students travel by bus. however this is not to suggest that the bus is the preferred mode, as more than % of those viennese bus users reported a preference for a different transport mode (stark et al., ) . fig. summarises the major barriers to dunedin adolescents using public bus transport to school: distance from home to school, cost, parental trip chaining, built environment features, the weather, the convenience of car-based travel, the public bus services, including their infrastructure and information, and safety concerns. although a study of hong kong adolescents found that perceived distance to public transport stops was a significant factor influencing active travel in boys (barnett et al., ) , distance to the bus stop was relevant in our study only when there was no service that came to that locale. in line with studies elsewhere (berggren et al., ) , waiting times and unpredictability of service were also significant factors in determining positive perceptions and use of public transport to school. nevertheless, it is important to note that fan and colleagues highlighted how transit users generally overestimate the time spent waiting but the presence of amenities, including benches and shelters, ameliorated this (fan et al., ) . this suggests that perceived wait times may be exaggerated, and highlights the important role infrastructure plays in overcoming these barriers. the norm of families dropping off and picking up their children by private car is consistent with the preference for car-based travel among dunedin adolescents (hopkins et al., ) . this leads to two important policy considerations. first, inflexibility of workplace has meant a home office option is rare; inflexibility of working hours precludes different start times that would allow different transport options, such as the bus, for both adolescents and their parents. recent experiences of homeworking during the covid- pandemic may, however, change attitudes to home-working as a feasible option for office-based workers on some, if not all, workdays or more flexible start and end times that suit families' needs better. skarin and colleagues pointed out the multiple ways in which household members affect each other's travel and recommended focussing on household context, not just individual travel behaviours (skarin et al., ) , and this is important here too. one fundamental issue is that of choice of school, which is both influenced by household resources and affects travel distances required and modes used (jarvis and alvanides, ; mandic et al., b; sandretto et al., ) . secondly, the idea that good parents show their care for their offspring through chauffeuring them around needs to be altered and socially sanctioned. this is particularly important given that parents play a critical role in decision-making about adolescents' mode of travel to school (mandic et al., b) . instead, the benefits of using public transport for adolescents' independence and health needs to be emphasised and be positioned at the centre of discussion, along with emphasising to adolescents the environmental impacts of their travel mode, as has been explored in denmark (møller et al., ) . fig. . common barriers to using public buses for transport to school. j.s. mindell, et al. travel behaviour and society ( ) - one encouraging aspect was the willingness of all school principals for their school and themselves to be included in this research. this is important, given findings in canada that lack of involvement of principals (and parents and students) was a key barrier to implementing a school travel plan effectively (mammen et al., ) . thus, it becomes clear that a multi-actor and multi-institution (including government agencies) response to shift attitudes and increase the adoption of active and public transport modes is required, which takes into account the relations between actors and institutions. from the findings of this research, a number of policy recommendations emerged (copland, ; copland et al., ) to encourage dunedin adolescents' use of public buses for school travel. policy recommendations for both city and regional councils focused on financial aspects, weather, safety and user needs. additional city-and region-specific recommendations were also outlined in the report prepared for the city and regional councils . it is clear from the research that there is potential for cities to learn from one another. literature on urban policy mobilities (e.g. mccann, ) has often focused on large cities, and between countries. however, our data suggest there may be much for small cities to learn from one another within one country. analysis of the policy documents revealed that economic growth and efficiency but not public health were the key considerations in transport policy in the period to . the exceptions were the strategic planning documents for dunedin, in which the effects of transport choice on the public's health was mentioned. there were also conflicting aims regarding public health. after this policy analysis was conducted, a change of government and of national priorities for transport in new zealand occurred, with different outcomes prioritised, including inclusive access, healthy and safe people, and environmental sustainability (new zealand ministry of transport, ). the land transport management act (new zealand government, ) mandated regional government to plan for 'transport-disadvantaged' people; which in dunedin results in bus stops being a maximum of m apart (in areas with bus routes). while this is beneficial in reducing inequalities in access, it minimises the amount of physical activity adolescents would obtain from walking or cycling to and from bus stops to levels unlikely to contribute to their health (duncan et al., ) . nonetheless, the free bus travel scheme for young people in london has encouraged greater use of bus transport for short trips without significant impact on adolescents' overall active travel , even when bus stops are in close proximity. policy-makers felt that enticing adolescents to use public transport for school travel is challenging in a society with an embedded car culture. however, interviews with policy-makers suggested a slow but positive change, with new investment in dunedin's public bus network and real-time information technology, at bus stops or using apps, to increase the user-friendliness of public transport and address some of the barriers mentioned by students, parents and school principals. cats and loutos found that although apps underestimate waiting times, they were much more accurate than timetables (cats and loutos, ) . alternative ways of funding public transport were also being explored by policy-makers such as a flat rate for young people. in london, the provision of free bus travel to adolescents had increased bus use and decreased travel poverty (jones et al., ) . the findings from our study were used to develop a set of recommendations to inform policy-makers . policy documents published in the past two years have shown some shift. the updated otago regional transport plan ( ), for the first-time, links public health concerns and transport. the nzta update of guidance on preparing regional transport policies focuses on public transport (new zealand transport agency, ). the version of the government statement on land transport recommends the importance of mode shift from private vehicle travel, particularly in urban areas, and commits to increasing funding for walking, cycling, public transport and road policing (new zealand government, ) . the strategic direction includes commitments to 'mode-neutrality' (i.e. considering all modes), reversing the previous assumptions favouring private cars, and to reducing greenhouse gas and adverse effects on the local environment and public health. the updated otago and southland regional land transport plan (otago regional council and environment southland regional council, ) has a focus on economic growth but also commits to improving both public transport and safe walking and cycling linkages (including creating a network of cycle trails in southern new zealand), as well as actions to reduce serious road travel injuries and deaths. in addition, recent policy recommendations for increasing active transport in new zealand also recommend improving public transport (mandic et al., , a . since transport contributes about % of new zealand's carbon emissions (statistics new zealand, ), the government will need to develop a strategy with clear goals related to modal shift to achieve the goals set in the recently approved carbon zero act (new zealand government, ). strengths of this study include the multiple sets of data in one city. the use of a comprehensive set of both qualitative and quantitative data provides insights on perspectives of potential public bus use from adolescents, parents, secondary school teachers, principals and policymakers and allows integration of those insights for a specific geographic context. limitations include analysis of data gathered in only one city, which limits generalisability of findings to other cities in new zealand or internationally. however, that applies to many other studies of travel. importantly, our findings are very similar to those of studies elsewhere. also, we used data collected over an -year period. however, the rates of adolescents using bus to school in dunedin remained unchanged between ( %; presented in the study) and / ( %) (mandic et al., a,b) . major barriers to dunedin adolescents using public bus transport to school included distance from home to school, cost, parental trip chaining, built environment features, the weather, the convenience of car-based travel, and safety concerns. if the goal is to increase public transport use for adolescents' school-related travel, effective policies could include: increasing parking prices to discourage driving and tripchaining for parents; improving bus infrastructure and subsidies; and by changing bus/bus users' perceptions (copland, ; copland et al., ) . these initiatives will require collaboration between different government authorities. a policy for public bus use by secondary school students should be developed to address parental, adolescents' and schools' concerns 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and walking in six new zealand cities factors influencing mode of transport in older adolescents: a qualitative study the household as an instrumental and affective trigger in intervention programs for travel behavior change results from new zealand's report card on physical activity for children and youth new zealand's report card on physical activity for children and youth. retrieved from auckland exploring children's school travel, psychological well-being, and travel-related attitudes: evidence from primary and secondary school children in vienna new zealand's greenhouse gas emissions [www document by foot, bus or car: children's school travel and school choice policy the beats research programme is collaboration between the dunedin secondary schools' partnership, dunedin city council and university of otago. the otago school students lifestyle survey was a collaborative project between dunedin city council, otago regional council, university of otago and otago secondary school sports association. we thank the researchers, collaborators, research students and research assistants who assisted with data collection, transcription, data analysis, and preparation of reports summarising findings from various studies reported here. we also thank participants in the various studies reported in this paper, including the policy makers who took part in interviews. in particular, we thank logan copland, who conducted part of the initial analysis on which some of the empirical findings are based, but who chose not to be involved in preparing this manuscript. supplementary data to this article can be found online at https:// doi.org/ . /j.tbs. . . . key: cord- - ucqudn authors: sun, ziheng; di, liping; sprigg, william; tong, daniel; casal, mariana title: community venue exposure risk estimator for the covid- pandemic date: - - journal: health place doi: . /j.healthplace. . sha: doc_id: cord_uid: ucqudn complexities of virus genotypes and the stochastic contacts in human society create a big challenge for estimating the potential risks of exposure to a widely spreading virus such as covid- . to increase public awareness of exposure risks in daily activities, we propose a birthday-paradox-based probability model to implement in a web-based system, named cosre (community social risk estimator) and make in-time community exposure risk estimation during the ongoing covid- pandemic. we define exposure risk to mean the probability of people meeting potential cases in public places such as grocery stores, gyms, libraries, restaurants, coffee shops, offices, etc. our model has three inputs: the real-time number of active and asymptomatic cases, the population in local communities, and the customer counts in the room. with cosre, possible impacts of the pandemic can be explored through spatiotemporal analysis, e.g., a variable number of people may be projected into public places through time to assess changes of risk as the pandemic unfolds. the system has potential to advance understanding of the true exposure risks in various communities. it introduces an objective element to plan, prepare and respond during a pandemic. spatial analysis tools are used to draw county-level exposure risks of the united states from april to july , . the correlation experiment with the new cases in the next two weeks shows that the risk estimation model offers promise in assisting people to be more precise about their personal safety and control of daily routine and social interaction. it can inform business and municipal covid- policy to accelerate recovery. history repeats from pandemic to pandemic (ghendon, ) . reducing the impact of pandemics relies on early detection and mitigation strategies that slow the spread to allow more preparation and reduce impacts on patient care. however, as the covid- pandemic continues to spread, the burden weighs heavy on all of us to control further spread and consequences through social distancing. lifestyles leading up to this pandemic are capable of spreading disease further and faster than ever before. new and more intense factors amplify disease transmission (dashraath et al., ) . the risks apply reasonably well to nearly all densely populated areas. environmental changes such as disruptive climate, may also contribute (ogen, ) . as coronavirus is monitored across the u.s., some communities see a diminishing number of cases, while others have yet to see the peak. reporting errors and delays also play a role in changes in disease incidence. an objective, publicly-accessible means to estimate risk of infection is needed in order to cope safely with the consequences of social distancing and sequestration. although various self-quarantine and self-isolation policies are in place in most of the u.s., the virus is not universally contained. people need to visit grocery stores, pharmacies and hospitals. they wish to attend sport, recreation and entertainment events, and community activities and family gatherings. considering the peak in coronavirus cases might have passed, some states have started to reopen business to restore the economy. risk assessment tools are essential in order to assist reopening with key information, as to where and when it may be safest to return to places of need or interest. reopening is a very daunting challenge for many businesses in the united states this year (workplaces, ). the duration of the pandemic is uncertain and its influence could last for a long time. the current guidelines for reopening are very general and not very customizable to accommodate the real scenarios of life in different communities. communities differ in population, store types, average visit time, patients, air quality, etc. there is no one-size-for-all solution to cope. a safer plan should be able to flexibly fit each circumstance by considering specific factors like the locally confirmed cases, potential asymptomatic patients, store space, layout, people density, local population composition, commodities, age distribution, capacity limit, social distancing, temperature check, violation enforcement, etc. however, precise recommendations are rarely available for business managers to use. very few quantitative models can estimate the impact of varying these factors. thus, few individual businesses can tailor their reopening policies to make smarter decisions in balancing life, safety, and economy. to find a balancing point between a full lockdown in fear of the virus and a plan of reopening businesses out of socioeconomic concerns, a mechanism to help assist that decision is urgent. the decision-makers to be supported include municipal policymakers, business managers and customers. the mechanism, or system, should provide a customized, real-time risk estimation for store managers, who may then adapt their operations to the unpredictable pandemic. an estimation of risk will also give potential customers the information necessary to assess their own risks of visiting businesses or other venues in an area, with increased awareness and confidence about their decision. to achieve that goal, this project proposes a straightforward social probability model based on the birthday paradox theory (if n people are selected at random, what is the probability that at least r people will have the same birthday?) (mckinney, ; wagner, ) to estimate the venue risk of people meeting at least one covid case, either asymptomatic, pre-symptomatic or actively symptomatic, in various public venues such as shopping centers, grocery stores, gyms, recreational areas, restaurants, dmvs (departments of motor vehicles), and federal agency public field offices. a prototype web-based system named cosre (community social risk estimator) (sun, a) is implemented to take zip codes as inputs and output a percentage value indicating the probability of acquiring the virus in the community. risk is calculated based on real-time data collected from public resources. the purpose of the tool is to give people a reasonable quantitative estimate of their risks of exposure to the covid- virus in their communities. pandemics are large scale outbreaks of infectious diseases that can increase mortality significantly over great geographic area and cause significant economic, social and political disruption (madhav et al., ). extensive global travels and long-distance contacts in human society raise the likelihood of pandemics. one recent example, the severe acute respiratory syndrome (sars) pandemic, was a critical threat to public health (ksiazek et al., ) . the world health organization compels member states to meet specific standards to detect, report on, and respond to infectious disease outbreaks. this international framework contributed to a more coordinated global response during the influenza pandemic than in the previous event (katz, ). global public health departments look to improve pandemic preparedness through refined standards and responding plans to flatten the time-incidence curves and reduce the deaths. management of community risks in a pandemic needs to apply more restrictive emergency management strategies than other hazards. the objectives of risk management are to strengthen our responding capacities to contain the diseases, enable and promote linkage and integration across the governments and societies. accurate estimation of risks is the first and fundamental step in making an effective risk management plan. common responding practices are to limit the point of entry to reduce the possibility of virus traveling. people, communities, states, and countries should continue to communicate with information and advice. precise information provided early and often will enable the community to correctly understand the health risks they face, and will make it easier to engage in actions to protect themselves. (who, ) the sars-cov- virus was first isolated from a patient with a pneumonia of unknown origin in wuhan, china. genetic analysis revealed that it is closely related to sars-cov- and genetically clusters within the genus betacoronavirus, subgenus sarbecovirus (cont, ) . although pathology studies have been done for the covid- disease, as an ongoing pandemic few tools are available to evaluate the real- time social exposure risks. an accepted classification groups risk assessment into several levels: little, lower, medium, high, very high, and severe. nicholas et al proposed a conceptual full-risk-spectrum, comprehensive pandemic risk management system (cprms) to prevent, prepare for, respond to, and mitigate the multisector impacts of severe pandemics (studzinski, ) . it contains six institutional building blocks in the global domain: governance and leadership, sustainable financing, information and knowledge systems, human capital resources, essential commodities and logistics, and operational service delivery. but the detailed framework still needs refinement in order to implement in each geographical area (studzinski, ) . in the covid- pandemic, there is still a long way to go to implement such a framework. the us centers for disease control and prevention (cdc) has developed an online tool called influenza risk assessment tool (irat) to assess the potential pandemic risk posed by influenza a viruses (cox et al., ) . the irat uses scientific criteria to measure the potential pandemic risk associated with each of the life scenarios mentioned previously. these criteria can be grouped into three overarching categories: "properties of the virus", "attributes of the population", and "ecology & epidemiology of the virus". a composite score for each virus is calculated based on the given scenario. the score gives the means to rank and compare influenza viruses to each other in terms of their potential pandemic risks. it is an evaluation tool, not a predictive tool (cdc, cromley discussed how to use gis technology and related technologies to analyze the geography of disease, the relationships between pathological factors and their environments (cromley, ) . to develop a predictive risk mapping of leptospirosis, an environmentally-driven infectious disease using j o u r n a l p r e -p r o o f spatial bayesian network was proposed (mayfield et al., ) . in a risk model developed for rift valley fever, exposure was measured as the proportion of total outbreak years for each district in prior epizootics, whereas the district's risk of outcome was assessed as severity of observed disease in humans and animals ( extended hierarchical spatial models to create spatio-temporal maps of disease rates (waller et al., ) . the methods of assessing and mapping the potential economic and public health risks associated with avian influenza outbreaks have been discussed (dudley, ) . olaf berke proposed an exploratory approach to map spatial relative risk using the background risk in the unexposed population. the results can reveal the importance and geographical distribution of unknown spatial risk factors (berke, ) . another paper offered a critical review of the methods of disease mapping and spatial regression based on male lip cancer incidence data in scotland (wakefield, ) . however, these existing models require input data that are unavailable or require contact tracing, or the targeted risks are not venue-based exposure risks. these researches have inspired and influenced our work, which proposes a new index to measure the community venue risks in covid- pandemic, but without contact tracing data. the idea of calculating birthday paradox probability (flajolet et al., ) is reused here. the probability distribution is similar to the binomial distribution (altham, ) . the basic formula is: where is the probability function of meeting someone with active disease; is the total community population (town, village, city, county, region, country); and is the total number of potential covid- cases in the area on day i and day i-d (defined as all accumulated covid hosts in the community at the given time, to include asymptomatic, symptomatic, hospitalized and self-quarantined; d is the average number of days that the disease takes for people to recover or die (~ days for covid- ); people who have recovered from the virus are assumed unable to infect others and are not counted in potential cases); is the number of the people in the business venue, e.g. grocery stores, shopping centers, gyms, restaurants, workplaces and recreational areas (sun, b) . first, we calculate the odds of not meeting any infected person and subtract those odds from to get the probability of meeting at least one infected patient in that specific group of people. this model assumes that all the people in the population visit a store with equal chance. if the chance is not equal for everyone, the values of and should be changed to represent their varying probabilities. for example, the population of fairfax county, va is over one million (census, ). the calculations for the maps in may differ from those for the april maps, a change based on physician discovery that most confirmed covid- cases will either recover or die within a -day window. the d for covid- is set to be days. for the may calculation, patient numbers for the same day in april (one month ago) are removed because they are no longer susceptible. as may has days and april only has days, we use april data in the calculation of may . this risk estimation model can help people to evaluate risk and react accordingly instead of panicking or just being indifferent towards the virus. the formula takes three parameters as inputs and the output is the probability of meeting at least one infected person in the store. the result ranges from to . the risk can be generally interpreted as the probability of exposure to another covid-infected person. besides, for policy making, it may be useful to classify the probabilities into several levels. for example: the risk less than % may be considered relatively low, - % means the probability is medium, - % reflect the place has a high probability for meeting a sars-cov- carrier, > % means the risk is very high and people might think twice before taking actions. this is just an example and the classification should be validated with real exposure data collected in businesses and public areas. based on the correlation analysis results, policymakers and community members will have a better understanding of the risk when going outside in the community and may take corresponding actions to avoid being exposed in their specific county. to evaluate the proposed risk score, we use several correlation methods to analyze its relationships with new case data for the next two weeks. for non-spatial correlation analysis, spearman's correlation coefficient (spearman's ρ) (spearman, ) , a statistical measure of the strength of a monotonic relationship between two variables, is utilized. its interpretation is similar to pearson's r (pearson, ) and can be used for analyzing non-linear relationships.. in addition, spatial autocorrelation analysis is used to study the relationship between risk estimates in one county and those in neighboring counties. if there is a significant correlation, a cluster will be generated to identify the hot spot regions (oster, ) . moran's i is the most common indicator for spatial correlation estimation. moran's i ranges from - to . using the proposed algorithm, we calculated the risks for all counties of the contiguous united states and generated a series of maps since apr , . fig. shows six of the maps on the dates of april , april , may , may , july , july , from which the trends of social exposure risks in the pandemic can be observed. the maps for june are similar to those for may and are omitted for brevity. the map of april (fig. a) shows that new york city, albany ga, new orleans, denver, salt lake city, and sun valley in idaho became the centers with highest exposure risks. on the contrary, the two states, california and washington, where the very first covid- patients were found, have relatively low risk. overall, the epidemic centers had emerged by april and began to spread among neighboring counties. at that time, from abundant news media accounts, most states had instituted social distancing and stay-at-home orders. these orders required people to stay at least feet apart and avoid gathering in groups. most mass gatherings were canceled following cdc guidelines. however, somee virus-affected people started to show symptoms and confirmed cases were reportedfrom coast to coast. as fig. (a) displays, almost every county showed social risk, but risks were low compared to succeeding months, with the exception of several states that exhibited outbreaks. on april st, risks were highest in the metropolitan areas of new york city, new orleans, and denver, and in blaine county, idaho, and summit county, utah. a potential outbreak could be foreseen from these areas as the time-incidence curves began to rise. the april map (fig. b) it is important to note at this point that state-to-state and region-to-region comparisons of critical parameters, such as confirmed cases or population-patient ratios, depend on consistency and calibration of methods, tools, training and, in some cases, infrastructure. with such inter-comparability, the information content of the raw data and model output increases in important ways, e.g., nation-wide priority allocation of medical resources and emergency assistance. covid- cases make a very high case to population ratio. unlike metropolitan areas, navajo county has fewer stores and public places, which would make it even risker if businesses reopen and people gather. also, in mid-april, the detroit and chicago metropolitan areas show signs of spreadingincidence. other regional differences appear. for example, risks of contagion in washington and california remain relatively low compared to outbreak centers in the u.s. south and east. florida shows a pattern of relatively high risk around miami and less risk elsewhere. the map of may (fig. c) shows that new york, pennsylvania, new jersey, and massachusetts are at high exposure risk in their coastal counties. new york city and its associated counties are the areas of highest risk. for these counties, the risk map highlights the importance of following health guidelines to wear masks and maintain social distancing in public places. . other east coast states, including maryland, virginia, washington d.c., north carolina, south carolina all turn darker red. inland regions, such as western pennsylvania, west virginia, western virginia, western north carolina, eastern tennessee, show relatively lower exposure risks. on may (fig. c) , the populous counties in the midwestern states like iowa, nebraska, ohio, indiana, kentucky, minnesota, have turned dark red. but there is less outward spread than in highly urbanized areas like new york. the risks are restricted in certain counties and show no obvious signs of a state-wide outbreak. those red counties are scattered and isolated. one explanation is that the other less populous counties intentionally reduced their contacts with the populous counties. the connections among different counties in these regions are not as close as those in the east coast counties. the risk in washington, california, nevada, texas, and florida, is rising slowly and remains lower than in the other outbreak states. according to the map of may (fig. d) , the riskiest areas are still along the east coast, however with a sign that risks may be on the decline in some suburban counties in new york, pennsylvania and, further south. in georgia, counties surrounding columbus county saw less risk, suggesting the new case load may have peaked. new york appears to show a downward trend in new confirmed covid- cases. high-risk areas on july (fig. e) and july (fig. f) include, high-populated counties in the mississippi basin and the corn belt states, which have become darker, and western counties in oklahoma and kansas show that coronavirus has spread further (fig. e) . also, risk across georgia, florida, texas, and louisiana has turned more serious, as has risk in southern california which has become higher after missouri. none show downward trend of covid- case incidences. however, in many of these states, stay-at-home rules were slackened in order to "reopen" and spur the economy. health experts warn that without data and without proper assessment, decisions to reopen will likely result in a spike of coronavirus cases. yet, the success of any reopening will depend on decisions made by each and every citizen. our research helps inform everyone's individual, smart choices during reopening. to evaluate the reliability of the cosre risk score, we validate its accuracy by comparing the risk score for a county with the number of new covid- cases confirmed in the following two weeks. a two-week interval was used because symptomatic patients are normally detected within two weeks of infection. fig. shows the spearman correlation analysis results. in fig. , the x axis is the cosre risk score at time t, the y axis is new cases per thousand people in the next two weeks after t. each spot in the plot represents a county. spearman's correlation coefficient is consistently above . , which falls in the "strong" category . that means a large cosre score is strongly correlated to more new cases in two weeks, and a small cosre score is strongly correlated to fewer new cases in two weeks. chances of coincidence are diminished because all the time steps have the similar correlation. the results show that the cosre risk scores well represent future exposure risks. specifically, the april results show that risks for most counties are below % while the new cases per thousand in two weeks are less than . on april the confirmed numbers surpass exposure risks in many counties (many dots are above the diagonal line). this is probably caused by insufficient testing in the early stage and the risk is underestimated. in may, the increase of risk scores doesn't correspond to obvious increase in new cases. the new cases per thousand for most counties remain under . one reason is that people became concerned and most states have stay-at-home orders in place. so even though the confirmed cases are climbing, the number of people with confirmed cases in public places are actually much lower than expected, resulting in low numbers of infections. things changed in july. stay-at-home orders in most states expired, and people gradually returned to normal life routines.. the spearman's r values are higher in july than in may, meaning that the increased new cases are more positively correlated to cosre risk score. in summary, the spearman correlation results indicate that cosre risk has a strong positive correlation with the new cases in the next two weeks, which suggests that the risk scores reflect real exposure risk when the quarantine orders relax or expire and people start to go back to normal life. figure . correlation between cosre risk score and the new confirmed cases in the following two weeks ( days); spearman's correlation coefficients are added in the tiles, the x axis is cosre risk score, the y axis is the new case per thousand people in the following two weeks. ( ) spatial autocorrelation and moran's i we calculated the global univariate moran's i of all the semi-month cosre risk maps from april to july. as shown in fig. means that for each county the restriction on in-person activities in public places in late april, may and june works to reduce risk. however, after entering july the correlation began to show significance between two continuous time steps; the county with high confirmed cases will very likely have a similar amount of confirmed cases at the next checkpoint. overall, correlation of the risk scores of two continuous time steps is positive and will have higher significance when venue activities increase. figure . the trends of global univariate moran's i and bivariate moran's i cluster maps based on local univariate moran's i between one county's cosre score and its neighbor counties are also generated to extract those counties that share the same pattern of case spikes or lower cases (as shown in fig. ) . a p-value less than . (typically ≤ . ) is normally considered to be statistically significant. we use . as p-value threshold to extract the significantly correlated counties; they are plotted in fig . all the colored counties have a p-value smaller than . , which means significant correlation between the cosre score of the county and its spatial lags. the high-high hotspot regions agree well with our observations in section . . the new york, new orleans, detroit, denver and seattle metropolitan areas and neighboring counties are the major hotspot clusters in april. in may, the chicago metropolitan area joined the list while seattle and detroit drop off, along with many major cities in the midwest states. the navajo nation became a hotspot and persists since then. in july, the new york and the other northeastern states turn blue after consistent low risks are observed. values less than . are considered as significantly correlated regions, and colored in fig. . the results show that cosre risk scores can actually reveal those hotspot counties on april , like those in new york, louisiana, and detroit; case increases in the next two weeks agree very well with model estimates in those regions. in all cluster maps, those hotspot regions are very consistent with the high-high regions identified in fig. , which means that the correlation between cosre risks and the new cases in the following weeks is significantly positive, especially in those hotspot regions and when little venue activity restrictions are in place. overall, our cosre risk shows reliable performance, with stable risk scores that indicate true exposure risks, from the early stage to the reopening stage. it should be clarified that exposure risk is not equal to the actual transmission risk. the community risk of exposure is an important contributing factor to the risk of transmission. the relationship is delineated using the following generalized equation: where "# ! $ " is the exposure risk in community daily activities, &! & is the infection risk. the two risks come from two steps. the former risk estimates the possibility of people coming in contact with virus hosts and sources. for example, people who stay home are at lower risk of exposure than people who go to the grocery store. the latter risk estimates the possibility of being infected by the virus after contact with a source. if people wear mouth and nose masks, safety glasses and disposable gloves and footwear, their contracting risk will be much lower than for people who wear no protections. ' $ ( represents the ability of the person or the community to be immune to the virus. people with antibodies could be immune to certain types of viruses and their immunity is higher. the transmission risk is inversely proportional to the immunity of the person or the entire community. the work reported herein gives a customized quantitative estimation on the social exposure risks of people who show up in public places. the results are tailored for every community by considering local at-risk population, store numbers, potential guest flow. the purpose is to help people increase awareness of their risks and help u.s. businesses adjust their store policies. following this guidance should accelerate the reopening of business while maintaining a low risk of virus contact for the wellbeing of both employees and customers. successful application of tools from this project will give both customer and business a clearer understanding of the risk of opening up and going to a place of business or recreation venue. decisions can be made on the fly. the correlation evaluation has demonstrated that the cosre risk score has a strong positive correlation with new cases for the following two-week period. the rate of new cases is basically determined by regional transmission risks in which the venue exposure risk is a preconditional factor. the positive correlation can be used as evidence to validate the accuracy and effectiveness of the cosre risk score. we would expect the score will serve as a simple, stable and reliable indicator to measure current risk and estimating new cases for the next two-week period. a reliable model designed for real-world application must consider many factors. more refinement is needed to improve accuracy of the three input parameters. for example, the model assumes that the confirmed patients comprise all the existing patients and all are free to move about the community; in reality, this is not entirely true. as an improvement, r should be used to calculate new potential covid patient numbers, as close to the real situation as possible. as official virus tests become more available, the ability to monitor and predict community-level risks amid a pandemic will improve. for the population, the model assumes that everyone in the population has the same chance of showing up in one store, which is also not true. individual preferences exist for which grocery store, shopping center, coffee shop or library to frequent. to make the model more realistic, one can obtain store visiting data from safegraph (safegraph, ), which allows analysis of the age, gender, and other characteristics of a store's customers. from this, a more accurate customer pool is possible based on the regional population census. one may also remove people from the customer pool who will not show up from the population used for calculation, as when data to populate the april and may maps of figure were adjusted to accommodate finding of physicians. further improvement will come by adjusting the real-time store visitation based on popular hours, business density, county income level and real-time customer counts. also, real-world exposure data are scarce. apple and google are among the exceptions with more accurate and more extensive data, where smartphone bluetooth has been used to trace potential coronavirus patients. based on patient tracing data such as this, the real probability of a venue with covid patients present could be compared with the estimated risks derived from our formula. since the pandemic is still ongoing, such a dataset is relatively sensitive and hard to retrieve at present. model evaluation with real-world data is our next step of work. public awareness of virus exposure risks is important. individual decisions will be made during a pandemic as people decide to leave home sanctuaries and reengage in social activities. to inform and assist, we propose a birthday-paradox-based probability model, coupled with a publicly-accessible web- based system to calculate community exposure risks in public gatherings. model derived risks are generated based on the real-time potential covid- cases, the population in local communities, and the number of people number in a given venue. with this web-accessed system, people may explore effects of the pandemic through a geographical spatiotemporal view, moving through time, and testing different venues and the expected numbers of people in them in order to assess changes in risk as the pandemic unfolds. the system integrates the risk estimation model, computational tools, and the analysis of evolutionary pathways, together with refinements to virus surveillance and to research-based, new understanding of this novel virus. the model and system proposed is an improvement in assessing risks posed by the sars-cov- virus and other virus outbreaks, epidemics or pandemics. we are subsequently better equipped to prepare and respond to the ongoing pandemic and to all future vector borne diseases. yet, caveat and caution are advised. the application scenarios of the system are made to be set in the middle of an outbreak or pandemic, after testing and tracking of patients are in place. today, without extensive and comparable national testing, the estimated risks might be far from reality. an important objective of our study is to show what can be accomplished with extensive testing and tracking, where methods, materials and objectives are comparable-where apples are compared with apples, without regard to state or region. valuable information can be drawn from the current web-based system. complex interactions among factors and inaccuracy of any or all of the input parameters will distort model from reality. we will continue to work to limit these distortions, improve accuracy and reliability through peer and crowd-sourced review. the authors would like to thank the anonymous reviewers, professor dieter pfoser, professor andreas zufle, and professor pat gillevet from george mason university, nasa project ( -haq - ) team members, the mit datathon team for their valuable advice. thanks for the covid- dataset provided by john hopkins university, the population data from u.s. census, and the foot traffic data kindly provided by safegraph inc. thanks to all the developers of the python libraries and tools used in this work. two generalizations of the binomial distribution geoda: an introduction to spatial data analysis, handbook of applied spatial analysis exploratory spatial relative risk mapping spatial relative risk mapping of pseudorabies-seropositive pig herds in an animal-dense region assessing real-time zika risk in the united states cdc, . influenza risk assessment tool (irat): questions & answers county population totals outbreak of acute respiratory syndrome associated with a novel coronavirus pandemic preparedness and the influenza risk assessment tool (irat), influenza pathogenesis and control-volume i gis and disease 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leptospirosis in fiji generalized birthday problem notes on continuous stochastic phenomena predictive factors and risk mapping for rift valley fever epidemics in kenya assessing nitrogen dioxide (no ) levels as a contributing factor to the coronavirus (covid- ) fatality rate trends in number and distribution of covid- hotspot counties-united states notes on regression and inheritance in the case of two parents proceedings of the pyshp: this library reads and writes esri shapefiles in pure python safegraph places patterns data the proof and measurement of association between two things comprehensive pandemic risk management: a systems approach. london: visiting international research fellow policy institute, king's college; cosre: covid- community social risk estimator what is the chance of meeting a covid- infected person in grocery stores estimation of the percentages of asymptomatic patients and undiagnosed patients of the novel coronavirus (sars-cov- ) infection in hokkaido, japan by using birth-death process with recursive full tracing a generalized birthday problem disease mapping and spatial regression with count data hierarchical spatio-temporal mapping of disease the authors would like to thank the anonymous reviewers, professor dieter pfoser, professor andreas zufle, and professor pat gillevet from george mason university, nasa project ( -haq - ) team members, the mit datathon team for their valuable advice. thanks for the covid- dataset provided by john hopkins university, the population data from u.s. census, and the foot traffic data kindly provided by safegraph inc. thanks to all the developers of the python libraries and tools used in this work. j o u r n a l p r e -p r o o f highlights:• a birthday-paradox-based probability model is proposed for estimating the community exposure risks in pandemics.• a web-based system named cosre is implemented to calculate the daily risks of each u.s. county in the ongoing covid- pandemic.• the model successfully reflected the early sign of outbreaks in covid- serious counties, including the navajo nation, new york, georgia, and louisiana.• the spatial correlation analysis shows the proposed risk score has significant positive relationship with the new cases in the next two weeks.j o u r n a l p r e -p r o o f key: cord- -h wj m u authors: keil, roger; ali, harris title: governing the sick city: urban governance in the age of emerging infectious disease date: - - journal: antipode doi: . /j. - . . .x sha: doc_id: cord_uid: h wj m u abstract: based on a case study of the severe acute respiratory syndrome (sars) outbreak in toronto, canada, this article suggests that we may have to rethink our common perception of what urban governance entails. rather than operating solely in the conceptual proximity of social cohesion and economic competitiveness, urban governance may soon prove to be more centrally concerned with questions of widespread disease, life and death and the construction of new internal boundaries and regulations just at the time that globalization seems to suggest the breakdown of some traditional scalar incisions such as national boundaries in a post‐westphalian environment. we argue that urban governance must face the new (or reemerging) challenge of dealing with infectious disease in the context of the “new normal” and that global health governance may be better off by taking the possibilities that rest in metropolitan governance more seriously. avian flu has begun to capture the imagination of world publics in recent years as the h n virus spread from its perceived origin in east and southeast asia to turkey and potentially to western europe (davis ) . newspapers and television corporations have discovered the pandemic as a topic of interest. governments, businesses, and civic organizations at all scales have drawn up preparedness plans. this newfound interest in the threat from emerging infectious disease has a recent precedent. in the spring of many parts of the world experienced an outbreak of severe acute respiratory syndrome (sars). in many ways, the sars outbreak is now being read as a stage rehearsal for what many public health experts believe will be a much larger epidemic once the h n virus, which has so far only spread from infected birds to humans, mutates and leads to direct human-to-human infection. sars, a previously unknown disease, is much different from h n but the way it was handled by health authorities around the globe can potentially teach us some lessons about future pandemic preparedness. this article looks at the urban governance aspect of these urban governance in the age of emerging infectious disease lessons. we rely on the rich and productive output in urban governance studies but will argue that this literature has had a particular blind spot: the relationship of urban governance restructuring to emerging infectious disease (eid). urban governance must be prepared to deal with infectious disease. at the same time, global health governance overall may be improved by realizing the possibilities that rest in metropolitan governance. a new "post-westphalian" constellation of post-national state power (fidler ) poses previously unknown demands on the governance of urban regions in the area of infectious disease control. while there has been much attention in recent years on the significance of global city regions in the new world economy (brenner and keil ) and while the governance and regulation of these regions has captured the imagination of academics and policymakers alike (buck et al ; harding ; heinelt and kübler ; kantor and savitch ; scott ) , little has been said specifically about the growing pressures posed by the potential threat of infectious disease through the global network on urban governance. rather than operating solely in between the often contradictory challenges of social cohesion and economic competitiveness, urban governance may soon have to be more centrally concerned with questions of widespread disease, life and death (agamben ) and the construction of new internal boundaries and regulations just at the time that globalization seems to suggest the breakdown of some traditional scalar incisions such as national boundaries. in making connections between the traditional discussion of public service provision between competitiveness and cohesion and the more dramatic and urgent questions about disease and health, life and death, we also consult work that has-in a foucauldian mannermore directly engaged with issues of (bio)power and governmentality (osborne and rose ; rose ) . for the area of urban planning and governance a more or less critical literature has begun to explore the spaces that cities have to maneuver in the rather open field of infectious disease preparedness planning and public health since the onset of the "new normal" after the attacks of / malizia ; matthew and macdonald ) . some work has explored the historical precedents of variations in how cities have fought infectious disease in order "to help us plan for the battles against disease that will be part of our future" (leavitt : ) . howard markel has put forward the observation that "[n]othing less than a cooperative partnership of nations, healthcare professionals, researchers, public health specialists, concerned corporations, philanthropies, and individuals will suffice to safeguard the world against the many public health problems we face today" ( : - ) . still, we believe more specific work needs to be done clarifying and determining the role municipal institutions of health governance can play in the global system of health governance. it is possible to view the sars outbreak of as a direct consequence of increased connectivity due to globalization in general and advances in transportation technologies in particular (brockmann, hufnagel and geisel ; guimera et al ) . in order to understand the effects of connectivity in the global city system on the health of people in these cities, it is necessary to develop new and innovative ways of thinking about what is connected in what ways in that system . there is a strong and growing consensus in the literature on globalization and health/disease that realities in a post-westphalian world need a rethinking of governance structures on a variety of scales between the global and the local (ali and keil forthcoming; fidler ; gandy b; harris and seid a; knobler et al ; lee ; markel ; mclean et al ; whiteford and manderson ) . in this article, we ask what the consequences of the connectivity for health governance will be. although public health policy delivery has always been an intensely local process, the "westphalian" state system had defined health policies in national containers ordered and segmented among others by world health organization guidelines but mostly under the sovereign jurisdiction of nation-states. public health was national health and health policy was national health policy under this regime. who interventions had to occur in the framework of national sovereignties, whose concern was with both popular health and economic welfare-not necessarily in this order (fidler ; heymann ; heymann interview, geneva september ) . when sars hit major metropolitan regions in asia and north america the need to rethink both global and sub-national health governance was exposed. the reliance on the hierarchical and hermetic system of nationally based health policy was put to the test as the who attempted to carve out a novel activist role in protecting global health beyond national interests and as sub-national governments, economic and civil society players moved to react to a localized global health crisis with coordinated action of their own (abraham ; fidler ) . at both ends of the redefinition of international health governance-the local and the global-an "institutional void" (hajer ) existed which could not be filled automatically by traditional, national health governance institutions and their international affiliates. we posit that urban governance will increasingly have to deal with questions of vulnerability and risk related to eids. vulnerability to eids is perhaps more pronounced in urban areas, where the majority of us live. urbanization increases the statistical odds that microbes are being spread (pennington ) . the aggregation of human populations into highdensity urban "islands" has important effects in providing the host reservoirs for maintaining infection chains (haggett ) . accelerated land use changes in and around urban areas have heightened the vulnerability of urban populations to infectious disease (patz et al ) . vulnerability is a notion which in close proximity to other "essentializing" western discourses such as tropicality and development (bankoff ) . it refers to a state outside of the west. yet, the notion of vulnerability has taken on renewed significance after september , particularly in the usa, as the "sense of security of many american citizens" was punctured (simon : ) . it has particular relevance to the case of sars which shattered the local public health and hospital systems of toronto, hong kong and singapore and the public perception of their safety. these cities' "globality" means that an infectious disease cannot be contained by a purely exclusive "local" strategy of public health. most vulnerability reduction policies tend to be largely limited to making safety modifications to key buildings and critical infrastructures, but the sars case illustrates that the human/cultural dimension must also be considered in the effective management of disease outbreaks in the contemporary global city. thus, isolation and quarantine did appear effective in fighting the outbreak, but what more could be done to prepare such containment strategies in case of future outbreaks in the global city? it is clear that we need to better understand the interactions of local modes of healthcare regulation in a globalized urban environment and the specific dimensions of urban vulnerability to public health threats in the global city setting (d'cunha (d'cunha , . global cities are usually considered a specific category of urban centres. they often have more to do with each other than with their immediate hinterlands and regions, and they tend to be more like other global cities than like other cities in their national networks (for an overview of the literature, see brenner and keil ) . as the case of sars demonstrated, global cities are not just switching stations for flows of capital and labour allegedly ordered in a tight network of privilege and command functions. they also are transfer stations of various and contradictory dynamics of the globalized economy. among them are city-country relations, connections between the developed and the developing world, even human-animal interrelations (brenner and keil ; sassen ; taylor ) . the sars virus is said to have travelled to toronto from hong kong through a chain of connectivities-or to use another term, an actor network-that includes the civet cat, live ("wet") animal markets, cross-border commuters across the spectrum of the labour market, hotels, transnational travellers, airports, healthcare workers, hospitals, etc. contributing factors were faulty or badly maintained aeration and plumbing systems in high-rise buildings, air travel in hermetically closed airplanes, hospital systems, diasporic relations among relatives, and so forth. at each link of this rather disparate chain, sub-connectivities are present, which we have called the capillaries of the global system: family relationships, small and parochial religious communities, more or less isolated (and even criminalized) food-handling practices, hospital hygiene codes, etc, all sub-realities of a larger global network of relationships. these subrealities are often not accounted for in descriptions of global cityness although they seem to be central to our understanding of certain consequences of globalization, such as the spread of eids. they are not just the micro versions of larger macro processes constituted elsewhere: they are co-constitutive of the global realities themselves. insofar as they belong to the larger processes of metabolism, these sub-realities are part of the ecological substrate of the global city system. we argue that it is exactly the dialectics of fixed infrastructures, built environments, institutional arrangements, reliable legal constructs, functioning hospitals (and their governance arrangements) of global cities on one hand and the unfixed, mobile, constantly re-articulated flows of people, non-human organisms, information and things that move through them, on the other. recognizing this dialectic also implies the critique of functionalistic and technological images of global connectivity in fixed network nodes. we rather postulate the topological, agency-founded co-constitution of such nodes gandy a; smith ) . urban governance has become a standard phrase in urban political studies. following jon pierre, urban governance can be defined as "the pursuit of collective goals through an inclusive strategy of resource mobilization" ( : ). as the focus of urban scholars has moved from "the comparative study of constitutions and city charters" to decision-making processes that involve state, market and civil society actors in all areas (gissendanner : ) , a broad spectrum of urban governance research has now been produced with case studies, comparisons and further theoretical developments (see, for example, brenner ; elwood ; harding , forthcoming; heinelt and kübler ; kantor and savitch ; kaufmann, léautier and mastruzzi ; pierre ; sellers ) . north-america-centred work on urban regimes, which continues to produce excellent case and comparative studies (for a recent summary of this literature see stone ) is complemented by a strong european-centred body of work of mostly comparative nature (brenner ; buck et al ; legales ) . in some of the literature, the shift to governance has been discussed in relation to the globalization and neoliberalization of cities, processes which in many cases have been seen as causative of this shift (brenner and theodore ) , while other authors have emphasized the role governance has itself played in facilitating these processes in turn. the comparative literature on urban governance restructuring has various intersections with the rescaling of the "political pathology" of infectious disease containment (fidler ) as the global and neoliberal contexts of current restructuring at the urban scale have been the focus of much theoretical and conceptual work. of these intersections, the new focus of metropolitanization deserves our specific attention. brenner's central concern, for example, is with the ways in which "urban governance has served as a major catalyst, medium, and arena of state rescaling processes" ( : ). new collective action at the city-regional level in the many traditional (e.g. economic development and social welfare) and emerging (e.g. environmental, (multi-)cultural) policy fields can be discerned in metropolitan areas around the world. public policymaking increasingly occurs at the metropolitan level as municipal and regional elites deliberately nurture this scale as the basis for international competition (boudreau et al forthcoming; brenner ). yet, there is also an emerging political space at the metropolitan scale, where collective action and claims for local democracy unfold. metropolitanization can mean an internal reconstitution of the political sphere and its articulation with civil society: "there is a diversification of local responsibilities and activities, from the production of local services to, among other things, a proactive role in economic development" (boudreau et al forthcoming) . among these responsibilities and activities may also be health governance at the urban scale. there is ample scholarship on the historical relationship between municipal government and disease both historically and on recent developments, such as the reemergence of tb, the role of urban poverty and diversity vis-à-vis disease or the ravages of aids (see, for example, craddock ; gandy and zumla ; raphael ; shah ). yet despite an increased interest in the relationship of globalization and disease (mcmurray and smith ), there has not been much attention on the specific urban governance aspects of eids in a world characterized by globalizing and global cities. we will argue accordingly that in the face of new threats to the health of urban dwellers caused both by increased technological, economic, cultural and ecological connectivity (globalization) and healthcare restructuring (neoliberalization), we need a renewed focus on the city as a place of potential or real disease and inversely as a place of health. an exception to the dearth of work conceptualizing health and disease as part of the overall governance of world cities has been the research of victor rodwin and michael gusmano ( ) on public health infrastructure in new york, london, paris and tokyo. while not explicitly locating their work in the governance literature, rodwin and gusmano ( : ) have noted: "urban health evokes contrasting images: the city as a center of disease, poor health, and enduring poverty versus the city as a cradle of historical public health interventions, innovative medical cures, and healthy lifestyles for the well-to-do". studying "urban health, particularly the evolution and current organization of public health infrastructure and the health status and quality of life in these cities" and the "important links between local, subnational, and central or federal authorities" (ibid: ) sounds familiar to students of urban governance. rodwin and gusmano have shown the impact of global cityness on localized health governance mechanisms and systems. in their work on new york, london, paris, and tokyo, rodwin and gusmano ( : ) have examined the impacts of "world cities-their health system and neighborhood characteristics-on two outcomes: the use of health services and health status". they found, not surprisingly perhaps, great diversity in which health is factored into the overall global city formation in these four leading global urban centres. their ongoing studies on various aspects of the public health system in these cities reveal the connections between common structural inequalities and social problems in global cities with their health systems. this work fills a void in the research on global cities generally and specifically adds to our understanding of the impact of globally induced social inequality-ie global city formation-on health. it also has the added benefit of being able to help us differentiate between the various health governance systems in cities as diverse as london, paris, new york and tokyo both in their centres and peripheries. rodwin and gusmano have identified four distinct "onerous health risks", which global cities such as toronto, hong kong and singapore confront: the re-emergence of infectious diseases; rising inequalities among social groups; barriers in access to quality healthcare by ethnic minorities and/or the poor; and terrorism and bioterrorism ( : ). all four themes stretch the notion of the city as a defined territorialized place. they point to cities as sites of topological relations that articulate activities and dynamics at various scales (amin and thrift ) . they define, to a large degree, the agenda of global city health governance. yet, as much as rodwin and gusmano's own research sheds light on the place-related aspects of health, it does not itself deal with the network-related aspects of health which is the aspect emphasized in the current article. we suggest adding two important dimensions of the analysis which we believe increase our understanding of the role of urban health governance in the fight against eids. first, the governance of cities today is unimaginable without the modern constitution of the "bacteriological city" at its base (gandy a, forthcoming) , which created managerial processes of a technological, engineering and scientific nature to guarantee public health and to lay the foundation of an economic development and demographic growth ostensibly unencumbered by the incalculable onset of disease outbreaks, which had wrecked urban populations and their economies until the twentieth century in europe and north america. it is on the basis of this century-old history that we now need to rethink urban health governance. a historical process of purification separated the modern city from its natural environments through a set of infrastructures and mechanized metabolic processes such as water and sewer infrastructure, garbage collection and processing, etc (kaika ). the "bacteriological city" as matthew gandy ( gandy ( , a has called the city of the twentieth century, was based on an entirely human-centred purified science, which "othered" animals, externalized disease and-in extreme caseseliminated "less-than-human" humans through technical ingenuity and government biopolitics (foucault ) . the bacteriological city kept the germs in check and allowed for new types of socially cohesive urban relations to take shape: "the emerging 'bacteriological city' involved a medley of different social, political, economic and environmental goals set within the context of a movement away from fragmentary and laissez-faire approaches to urban governance" (gandy : ) . this rationalization of urban governance via technologically reliable networks was based on a universalist interest in public health advances. the currently popular "neoorganicist" view of the city, of which the materialist notion of the cyborg city is a critical extension, puts a new spin on the tradition of the bacteriological city. it has been strongly associated with a transhumanist view of our urban reality, in which, as bruce braun observes, "'barely human' others (iraquis, rwandans, muslims), and 'almost human' companions (monkeys, dogs and cats), are discussed alongside accounts of 'inter-species' exchange (bird flu, sars) in which the boundaries of the human are suddenly porous and mobile" ( : ). such mixing clearly has consequences for governance as the carefully guarded distinctions between people and germs, materialized in the modern bacteriological city, are now being challenged unexpectedly. as a consequence, we now need to figure out collectively where to draw the kinds of regulative boundaries, which we humans may need to survive the imagined or real onslaught of the germs. and such defensiveness is most likely tied up with the regulation of bodies-human and nonhuman-that carry or are suspected to carry the disease. technically, while not necessarily ethically, the sacrifice of millions of ducks or cattle as a reactive of preventative public health measure, is the same kind of measure as airport screening for foot and mouth disease and sars and quarantine of suspected bodies in cities. braun challenges us to think that it is: possible to understand cities, for example as "posthuman" assemblages in ways that both vastly expand our understanding of the actors shaping the urban experience, and that confound our usual understandings of the space and time of urban life . . . writing the sars virus into a "posthuman" toronto explodes the time-space of the city, folding people and animals in china and thailand into bodies on queen street, and revealing time to be multiple and rhythmic-the time of circulation of people and capital but also molecules ( : ). lastly, disease and health have important impacts on the rearrangement of the governance of public/private space. hospitals, quarantine, cultural spaces are fundamentally reassessed and their place in the order of public and private everyday lives and official geographies is recalibrated: what is acceptable in terms of use of space by various bodies in cities? our argument is that while purification and biopolitics were the characteristics associated with the hygienic city of the last century, we have now entered a phase in which the potential reemergence of infectious disease at a mass scale forces us to rethink the relationship of our built environments, our institutional arrangements and our practices as urban dwellers. this has to do as much with the changing nature of cities as basing points of the global economy-to use quite a conventional concept from global cities theory-as with the kinds of reemerging diseases we now have to deal with. second, it is necessary to extend our view beyond the national institutional level when looking at the governance of eids in cities, as extra-national organizations such as the atlanta centers for disease control (cdc) and supra-national organizations such as the world health organization (who) exert significant influence on urban health governance in any country, sometimes not even mediated through national policy or institutions (fidler ; heymann ) . in a global perspective maarten hajer has noted a particular "institutional void": [m]ore than before, solutions for pressing problems cannot be found within the boundaries of sovereign polities. as established institutional arrangements often lack the power to deliver the required or requested policy results on their own, they take part in transnational, polycentric networks of governance in which power is dispersed. the weakening of the state here goes hand in hand with the international growth of civil society, the emergence of new citizen-actors and new forms of mobilization ( : ). municipal public health policy emerges in a context of larger-scale dynamics over which it has little control. global cities and city-states such as toronto, hong kong and even singapore are burdened with responsibilities due to their rising integration into world city networks on one hand and continued lack of self-determined decision-making powers for their complex jurisdictions on the other. in addition, cities like toronto are tied into an increasingly diverse global network of diaspora and migrant cultures at the base of their hybrid globality (goonewardena and kipfer ) . the connection between the globalizing political economy and the cultural and demographic changes it brings with it are crucial to understanding the everyday practices and socio-cultural interactions that characterize today's world and more specifically the everydayness of global cities. toronto-like other cities in the global city network and elsewhere-has taken on far-reaching responsibilities for the settlement of immigrants. this has become a central concern of metropolitan governance now. as in past waves of immigration, cities have become the actual border points for new immigrants. it is important to remember, as nicholas king has reminded us, that under these circumstances, "researchers and public health officials would do well to think in transnational as well as international terms. this means focusing less on the transgression of borders by individuals, and more on the formation of transnational connections between spaces and populations once thought to be disconnected or insulated from one another" ( : ). of course, urban governance is just a fraction of an overall system of health governance, which in the words of fidler ( ) now has to deal with sars as the "first post-westphalian pathogen". fidler also reminds us that as sars represents new problems for public health and creates the need to develop diagnostics, treatments and vaccines in the context of globalization, it breaks down both the sub-national and international framework in which public health has been governed for more than years. in particular, the sars outbreak posed a threat to commonly held views of national sovereignty which allowed nationstates to deal-vertically-with their own health systems internally while negotiating (ideally) at par-horizontally-with other nationstates internationally. the experience with sars points to an interesting dialectics: the existing system is both corroded and withstands the onslaught of the virus. speaking about the us, fidler states, "federalism constructs political borders between federal and state governments. germs no more recognize these borders than they recognize international borders. federalism does not, however, disappear as an influence on public health governance simply because germs do not recognize the boundaries it creates" ( : ). fidler's "political pathology" is pivotal for the understanding of the parameters of health governance today. he carefully charts the landscape of international and now global health governance since the nineteenth century, when the first international sanitary regulations were drawn up among the great powers of the world. these efforts eventually led to the creation of a world health agency, the who, which has operated on a set of tenuous global regulations such as the international health regulations, which have recently undergone redrafting to reflect the specific challenges posed by the fight against sars (fidler ) . the weakness of fidler's otherwise sharp analysis is that it focuses only on one direction of the rescaling of international health governance towards the global level. in answering the question "how to manage borderless bugs in a borderless world", fidler concentrates on the role of new global institutions as well as new non-state actors in the health field. both, he correctly states, narrow the traditional sovereign spaces of health policymaking, even of large states such as china which-begrudgingly-ceded some of its authority to the who during the sars crisis after initially lying to the world about the severity of the disease in its provinces and in the nation's capital. the who emerged as a stronger and more recognized player from the sars crisis and established, for the first time and if only briefly, a global community of eid management (fidler : ; heymann ; preiser ). fidler does not engage with other forms of the rescaling of the westphalian state system such as the one brenner has defined as "metropolitanization" (brenner ) . we have been arguing throughout this article that this metropolitan scale of governance deserves more attention in the regulation of an urban-based global reality. in fact, as the former director general of the who underlined, "who officials every day deal with local communities and officials, around the world" (brundtland, email interview november ). although, in the past, cities have often been directly blamed or linked to disease (gandy : ) , this pattern was supposed to have been superseded by the modernity of the cities themselves. until not too long ago, cities in the west were considered free of catastrophic disease of the traditional epidemic kind. thomas osborne and nikolas rose noted only as recently as that we could observe a shift from a focus on disease to a focus on health in the governance of cities: the city has long been imagined in terms of sickness and health. but in recent decades a new image of the healthy city has emerged: the city as a network of living practices of well-being . . . the very idea of disease in the city has been transformed. it is no longer imagined in epidemic form-the invasion of the urban milieu by cholera or typhus putting its inhabitants at risk of infection. rather, disease and ill health more generally, is imagined in terms of activities (diet and coronary heart disease . . .) and relationships (unsafe sex and hiv . . .). we no longer have the sick on the one side of a division, the healthy on the other-we are all, actually or potentially, sick, and health is not a state to be striven for only when one falls ill, it is something to be maintained by what we do at every moment of our everyday lives ( : - ). recent developments in the wake of sars but also scenarios following a potential outbreak of an epidemic of either a new flu strain or a human form of the avian flu have belied the disappearance of epidemic disease from the urban experience as expressed in this quote. not only is it not true for most cities in the world where people keep being threatened by infectious disease pandemics of all kinds, it is also not true for western cities anymore as sars has shown in utmost clarity. we do agree with osborne and rose, though, when they point out that the governmentality that regulates disease has shifted from the collective to the individual. this is a major biopolitical shift which is mostly played out on the level of urban governance. this interpretation coincides with other work on the changing nature of public health (petersen and lupton ) , which argues that health and disease have been recast as individual responsibilities rather than social ones in the contemporary period [see also sanford and ali ( ) for an elaboration of this argument with respect to sars]. it is exactly this-neoliberalgovernmentality of individualized notions of health and sickness which existed when sars arrived. it is in this framework that we have to understand the new thinking and agency around infectious disease in the city. it adds to the general shift in the current city from traditional notions of control in favour of a more clearly orchestrated mix of state and market interventions. public health governance in the age of sars has-at least potentially-moved to a bundle of strategies that fit well into the overall securitization of urban society which includes "enhanced forms of social control through a mix of architectural, ideological and intelligence-gathering processes" (gandy a: ) . in addition to these developments towards a new governmentality of public health, the sars crisis occurred in a very specific environment, which had been created by the events that followed the attacks on washington and new york city on september , . shortly after september , , american vice president dick cheney was reflecting on what he called a "new normalcy", a notion that was used widely at the time to legitimize changes to long-held understandings of the social and legal makeup of american society (lawyers committee for human rights ). legal scholars and practitioners as well as political pundits and activists of all stripes pondered the meaning of the "new normal" and pointed to the deterioration of basic human and civil rights in the aftermath of the september and subsequent war-related events. "living" in the "new normal" became an object of serious study (simon ) . a legal study examined such changes in the areas of "government openness; personal privacy; immigration; security-related detention; and the effect of us actions on human rights standards around the world" (ibid). while admitting to the necessity of some government action in the wake of / , the report notes "dramatic changes in the relationship between the us government and the people it serves" and voices many grave concerns about the deterioration of civic and individual liberties. beyond its immediate denotation with respect to the changing times after / , the term has since thrived as a powerful (if somewhat clichéd) metaphor that has been bandied about in all kinds of contexts. and despite the clearly problematic context in which "the new normal" was introduced into the political and vernacular vocabulary-or perhaps precisely because of the implications of this context-the term found a wide use in toronto's sars outbreak of . during the crisis politics of the day, particularly in the healthcare system itself and among the politicians involved, "the new normal" quickly became the buzzword for an overall state of emergency that gave policy actors and decisionmakers license to make unprecedented changes and to call for reform of major threads of the social fabric, particularly in the area of public health. the "new normal" became the umbrella term for a situation in which thousands were put into quarantine (or if they resisted into isolation), and nurses-many of whom were infected themselves-were missing from understaffed hospitals, at a time when the overall system of healthcare delivery was admittedly about to "snap" (boyle ) . one of the main users of the concept was the ultra-conservative minister of health for ontario, tony clement, who, for a moment, surfed on the popular wave of the giuliani-brand "roll-up-your-sleeve" and "openshirt-collar" politics of emergency, which swept him into the public spotlight in the spring of . clement became the public face of a social crisis which had repercussions for much more than health policy per se, and touched on issues involving labour relations, "race" relations, multiculturalism and much more. the "new normal" soon became the yardstick for all these types of issues. for instance, in a dispute with nurses about the lack of full-time positions and the potential change to the funding formula, clement said on may : "in the 'new normal' those kinds of things would have to be reviewed through the prism of infection control". around the same time, clement's ministry issued a "backgrounder" in which the "new normal" was "characterized by high standards of practice that reflect a heightened awareness of emerging infectious diseases including sars" and where there is mention of a "'new normal' environment", in which healthcare workers are meant to operate. one set of directions for the faculty of medicine at the university of toronto dated june , stated self-reflexively: the term "new normal" has already become a bit hackneyed in the face of a second wave of sars in toronto. nonetheless, it is a useful term to encapsulate the change in thinking that may be necessary if we are to achieve longer-term containment of sars and any similar illnesses that may come at us in the future (http://www. library.utoronto.ca/medicine/sars/sarsupdate.pdf; emphasis in the original). at other scales, a toronto family doctor, for example, used the term in a "sars diary" she published in a professional journal and concludes, after relating her ordeals of operating under conditions of quarantine: "i guess this is the new normal i've been hearing about" (greiver ). yet another voice was the director of the reputed american centers for disease control in atlanta, julie geberding, who referred to diseases like sars and monkeypox as the "new normal" while addressing a meeting of the american medical association in chicago in . the connection of the "new normal" to state protocol in its dealing with citizens in an anti-terrorist effort is neither surprising nor unintended by those who make the link. the very notion of the "new normal" signifies the intrusion of unusual measures in our everyday lives, in which leaders have to be cut slack in making decisions about political rule, when regular law and understandings of rights become irregular or non-normal. the invocation of legitimized state violence-be it in anti-terrorist war or in imposing quarantine on groups within an urban community-through the concept "new normal" is itself becoming an accepted part of what we consider tolerable. the "new normal" changed both the horizon of expectation, which citizens, users of the healthcare system, travellers, etc may have had and the potential range of action for governments in dealing with the crisis. it has led, at a remarkable rate, to a lowering of democratic potential in the making and practice of policy, in this case health. the rights of both patients and healthcare workers were considerably cut back during the toronto sars crisis. this is true precisely because the crisis transformed a group of previously relatively obscure public health officials and politicians into a group of well-known leadership personalities-donald low, marcia taylor, doris greenspun, colin d'cunha, sheila basrur, tony clement, james young-who took care of democracy while it was dormant in the shadow of the "new normal". this "decisionism with a populist face" was an interesting development not in tune with the zeitgeist of moving from government to governance. it was, however, very much in line with the notion of "performativity", as sars and the crisis it brought to urban society, was "performed" by more or less media savvy actors, who were always only minutes ahead of the general public and the press as the epidemic progressed and ultimately subsided. at the other end of the spectrum of agents "performing" the sars crisis was the ill-fated and pompous appearance of toronto mayor mel lastman on cnn at the occasion of the who's travel advisory against toronto. lastman, ignorant of the context of global health governance in which "his" city found itself and apparently unfamiliar with the who, spouted out venom against the un organization which, in his eyes, unduly interfered with toronto's self-governance. these actors/agents were put on stage by the arrival of the virus and they played "crisis" and invented a new mode of governance as they went along. while they were by no means unprepared for the epidemic, public officials joined regular citizens in performing a disease that no one yet knew. through the ways citizens and experts in toronto (and singapore and hong kong and elsewhere) performed the disease, the world learned about sars. it seems that the "institutional void" hajer ( ) sees emerging in this context was filled, at least on an ad-hoc basis, by rapid policy change in an emergency situation created by the potentially catastrophic threat posed by sars. the ideological precepts of the "new normal" enabled the state to reassert itself as an active participant in public life after neoliberal reforms in ontario had stripped its involvement in many areas of public welfare to the bare minimum and to reinsert itself with some legitimacy in a policy community which had learned to not trust a government that had de-funded public institutions such as healthcare and education at an unprecedented scale (keil ) . this kept the ontario government "in the game" at a critical time-at least until such measures were challenged by the general public, healthcare workers' associations, patients and their relatives and the press. the loss of clear boundaries for jurisdictions is, of course, a direct outgrowth of global city formation and the growing incapacity of the (local) state in particular to deal with crises visited upon an urban region by its growing internationalization (friedmann [ (friedmann [ ] . the growing challenge presented by global city formation to the fiscal and institutional capacity of the local state is exacerbated by the processes invoked by hajer but also by the ongoing re-scaling of political spaces in a rapidly changing world. specifically with respect to global cities, it has been noted that conceptually and pragmatically the business of municipal politics as well as the conduct of everyday life has been both de-localized in profound ways through economic and cultural globalizations, and re-localized through the idiosyncracies of topologies, which bring together the myriad social connectivities in the microcosms of the world's urban centres (smith ) . urban health governance is embedded in a larger system of urban governance with its vertical and horizontal ties to other levels of government and into civil society and the private sector. urban governance in toronto had been characterized by the city's forced amalgamation in , which initially changed the landscape of public policy significantly towards a more competitive, coercive and stratified environment. this coincided with fundamental changes to municipal politics and internal governance processes as the city has been trying to establish a sense of harmonized "good government" and civic engagement after amalgamation. the outcome of these processes was contradictory: on the one hand hardcore neoliberal reforms were rolled out and downloaded by the tory provincial government between and and often followed through by a conservative and boosterist mayor mel lastman who was unapologetically the spokesperson of an aggressive business lobby and particularly the development industry; on the other hand, progressive politicians at the municipal level with the support of a continuously active social and environmental movement sector, the public sector unions and an electorate which had not forgiven the tories for their attack on toronto political traditions. the result of these contradictions was that urban governance in toronto at the time of the sars outbreak was split as continued reform in the municipal administration, and certain "forgotten" policy areas such as food, homelessness the environment-and public healthcompeted with neoliberal development mantra of a business elite which began to use the newly amalgamated city as their strategic terrain for interurban competition. inside the municipal administration, departmental restructuring and harmonization had led to insecurity, at least temporarily, as to the procedures and substance of urban policy when political cultures of suburban jurisdictions were melded with the downtown's more progressive, democratic traditions, which had led to more sustained rights claims of more diverse populations. this progressive city/conservative suburb split in the geography of toronto's urban governance was challenged by the new immigration and settlement patterns, which made suburbs more diverse than the inner city and the inner city potentially less dynamic politically than the multiculturally invigorated suburbs. during the time of the sars outbreak, this shift complicated matters significantly as the crisis was played out in geographic and social areas of the city-scarborough and north york-which remained largely terrae incognitae to the old toronto elite. the sars crisis intersected with business as usual in urban governance in as far as it was recast quickly from a health crisis to an economic crisis once the worst of the outbreak was over. the worry among toronto politicians and business people over lost business in tourism and entertainment fell in line with the usual propensity of urban officials and civic leaders to heave their city above its competitors in economic development, cultural creation and tourist attraction. in this sense, the sars crisis interfered with the strategic goals of the governing regime of toronto and the governing institutions that had created their success. the peculiar balance of social, economic, environmental and state interests in elite and popular circles that made up the governing coalition of the urban region was threatened by sars, which was contextualized in a series of setbacks for the region's economic progress and civic self-esteem, the loss of the bid for the olympic games to beijing in particular. the question was how these changes contextualized health governance in a time of crisis. the institute on governance defines health governance in canada as follows: in canada, the governance of healthcare is built on intergovernmental cooperation, reflecting a formal division of powers regarding healthcare as outlined in the canadian constitution and the charter of rights and freedoms. in addition, governance of healthcare also takes place outside the governmental sphere. this complexity requires organizations, sectors, regions, first nations communities and governments to forge capacities to govern (http://www.iog.ca/ knowledge areas.asp?pageid= , accessed november ). the institute proceeds to define the most pressing healthcare challenges in canada as follows: • critically assessing the alignment of health governance structures and processes with best practices. • reframing the understanding of governance as expanded beyond an individual institution to include mutual accountabilities among providers. • building ways for health providers to share information and work in a complementary way. • strengthening boards of directors, particularly in hospital governance. • building stronger relationships between voluntary sector organizations and government and between the various levels of government, including first nations (ibid). while clearly open to the complexity and multi-scalarity of health governance, this list of priorities is also characterized by a glaring absence of any reference to the role of cities in health governance. this absence is two-fold. there is, on one hand, the traditional obscurity that municipal politics suffers in the canadian state architecture (keil and young forthcoming); on the other hand, there is a more general eclipse at work here which disregards or even dismisses the role of urban governance in the management of societal matters in a post-westphalian world. we believe, though, that urban public health authorities and their associates in local hospitals, urban non-state actors in the health field as well as workers in urban medical settings have played an important role in the detection, identification, monitoring and fight against eids in particular (interviews july to december : toronto public health official, associate medical officer of health-toronto, university hospital network official, microbiologist-in-chief-toronto hospital, ontario nursing association official, public safety and emergency preparedness canada official). they have provided the core responsibilities of public health-assessment, policy development, assurance-often without support and sometimes in conflict with and in contradistinction to higher level health authorities (rodwin and gusmano : fn). one analysis revealed about the ontario situation during sars: the province of ontario was ill-prepared to deal with an infectious disease threat on such a scale. in canada, the provision of healthcare, including public health, is a provincial responsibility. however, the financial and operational responsibility for public health had increasingly been shifted to municipalities such that, at the time of the sars outbreak, funding was shared equally between the two levels of government. this funding shift created a decentralised public-health system, with the province's public-health units operating quite independently of each other (lim et al : , emphasis added) . sanford and ali ( ) have documented aspects of "new public health hegemony" in the response to sars in toronto. they specifically argue that there has been a mix of old and new measures at various scales that was pervasive and that overall a new hegemony around new epidemiological techniques, risk management, morality and security took shape. extending this work to the specific context of urban governance, a number of preliminary observations can now be made in order to characterize the urban health governance challenges identified in toronto during and after the sars outbreaks of . the urban health governance system experienced a very specific set of pressures, which spoke to the kinds of fundamental decisions that have to be made by urban-scaled and municipal authorities in a moment of epidemic disease. affonso, andrews and jeffs ( : - ) have perceptively identified three sets of paradoxes that led to three sets of dilemmas in the governance of the sars outbreak. these paradoxes/dilemmas were, first, that healthcare workers became sources of transmission and active sustainers of the sars case matrix (leading to the dilemma to be forced to decide whose safety gets priority: patients or caregivers?). second, hospitals were sources of sars infection in the community, breaking down the boundaries of medical care and community in threatening ways (leading to the question of how far do providers of healthcare have to go to provide safe spaces?). third, a culturally and ethnically diverse city may be particularly vulnerable to infectious diseases (prompting the question about the relationship of civil liberties and disease control). in terms of urban governance, these three couples of paradoxes and dilemmas denote spatio-institutional uncertainties of a new kind, which challenge traditional modes of integration and regulation of economic institutions (labour markets/work places), specialized functional spaces (hospitals), public institutions (public health agencies), codified private behaviours (patient versus citizen rights), etc. in an urban governance model, questions need to be directed at the particular ways through which state action (public health, security, etc), private sector involvement (providers of masks, medical equipment, drugs, etc.) and civic organizations (ethnic initiatives against racism, protection of workers' rights, etc) and individual civil rights claims (patients, quarantined individuals, travellers, etc) are coordinated by whom, at what scale and with what procedural democratic means. affonso, andrews and jeffs ( ) make a number of incisive and plausible recommendations as to how to improve health governance in future outbreaks of the kind endured in which centre around patient safety and workforce safety, spatial profiling and risk assessment, as well as community mobilization ( : - ) . it is important to note in the context of the question of urban governance before us that each of these intended measures would have a tangible impact on the day-to-day business of governing cities through democratic political rather than managerial-administrative processes at the municipal level. the core dilemmas these processes would face in the reality of current canadian municipalism is first the lack of autonomy local agencies have in the face of an unreformed federalism, which sees cities (and their institutions) as mere units of the administrative state (of the province and canada) and not as political decision-makers on their own terms; and second the tremendous weakening of lower state and governance structures-often despite rhetorical statements to the contrary on the effect of devolution and subsidiarity-in the face of the globalization and neoliberalization of the canadian state, including the increasing porosity towards supra-national institutions such as the who. we have some evidence on how the local state institutions in toronto themselves saw the crisis and what lessons they suggested to draw from it. the former provincial medical officer of health, colin d'cunha ( ) , detailed the various lessons learned from the outbreak, mostly through the lens of health reporting. the provincial scale is extremely important in the canadian system where municipalities are dependent on upper level policy frameworks and financing without much autonomy for local agencies and institutions. urban governance is severely constricted and clearly defined by this situation. while the municipal state may also be the most politicized of the three levels of government, it remains under the tight supervision of the province in particular and while state expenditures have risen consistently since the s in the federal and provincial governments, municipal funds have not kept pace with the demands placed on them through decades of downloading and devolution (villeneuve and séguin, ) . d'cunha, whose provincial agency was responsible for local health units in ontario, notes in particular that the reportable disease information system in place when sars hit, had been introduced in the s. a new system of reporting, the integrated public health information system (iphis), although available since early in the century, was only to be implemented in the spring of and was further delayed through sars. the provincial level system of surveillance was tied in with the global public health intelligence network (gphin). the provincial health protection and promotion act (hppa) makes mandatory disease reporting and control. it was amended after the sars crisis to empower the province to facilitate isolation of infected individuals (d'cunha ) . d'cunha's office was also left in dire straits in the wake of serious de-funding of public health institutions at the provincial level under a tory government after . the provincial health authority appeared very much like an empty shell which had coordinating functions of local authorities but could not muster the resources to do a good job giving direction and provide credible leadership to municipal and regional agencies (interview, associate medical officer of health-toronto, october ) . in the context of this legal and institutional framework, local-scale health agencies do their work. sheila basrur, the former municipal officer of health, and co-authors have noted that the main roles of toronto public health during the outbreak were case investigation and management, identification and quarantine of contacts, disease surveillance and reporting, health risk assessment and infection control advice to health institutions and other community settings (basrur et al : ) . the sars crisis posed a significant stress on the already severely compromised public health system of toronto as other public health services were cut or reduced to "essential services only" (ibid: - ). the kinds of measures under the responsibility of the municipal public health hegemony reflect the temporally layered and overlapping traditions stemming from the "bacteriological city", updated and redefined through more recent developments. the point to note in this respect is the often confusing unevenness in measures from various periods, phases, and moments of urban governance, which were haphazardly re-grouped into a recombinant mix of place-specific sets of trials and errors. while the coercive and enabling qualities of an existing municipal public health system were tested daily with unexpected twists in the proliferation of the disease, a new administrative reality emerged in the shadow of the successes and failures of an iterative policy process. cases of temporal unevenness were, for example, the deployment of quarantine and isolation orders for the first time in years (with no living administrative memory of and hence no experiential knowledge with such measures in the system) and the much younger (but failing) -year-old provincially authorized surveillance system (which had not kept pace with both technological advances and procedural necessities that had occurred since its inception) (basrur et al ) . the unevenness here related in both cases to the fact that two measures at two ends of a developmental scale in public health measures-the rather traditional and rather blunt tool of the quarantine, and the biopolitical, yet informationalized surveillancewere potentially at odds with the constituencies and clienteles they were meant to protect (and whose general rights sensibilities were a far cry from the mid-twentieth century) and, in the case of the failed surveillance, certainly not up to the challenge that the sars outbreak posed. one influential way to understand the local state is to see it as a sphere of influence of both the state and civil society (kirby ; magnusson ) . civil society is dramatically redefined in the context of the "new normal". in the immediate crisis in the spring of , it became rapidly clear that the "new normal" was not just a rewriting of a few hospital protocols and ministry directives. in true fashion of creating a new "governmentality" through new "technologies of power" in the foucauldian sense (osborne and rose ), the "new normal" became a new standard of societal interaction overall, accepted and even disseminated by the "normalized" everyday actions of urban residents, and the yardstick of urban governance. as we are writing this, toronto is going through emergency preparedness week, which calls on everyone to do their part in putting obstacles in the way of harm. the event organizers are clear that they expect citizens to do their part when taking in exhibits under "the theme 'what are your reasons for being prepared?' the city's exhibits will help toronto residents increase their awareness of emergency-preparedness issues and answer this question for themselves. residents will have the chance to speak with representatives from the city's co-ordinated emergency response teams, view emergency equipment, and pick up important personal emergency preparedness literature" (http://www.toronto.ca/wes/ techservices/oem/index.htm, accessed may ). while civic duty is part of the overall deal, awareness of the possible pitfalls of running a society on an emergency mindset are also part of the public debate. gro harlem brundtland's powerful statement that "with globalization, a single microbial sea washes all of human kind" (quoted in harris and seid b: ) stands as a starting point of our considerations here. like brundtland, who was the director general of the who during the sars crisis, "hundreds of thousands of men and women around the world devote their working lives and intellectual creativity to protecting our health" (markel : ) . that they do this in a wide variety of institutions-state and non-state; private sector and civil society basedand that they are crossing boundaries of disciplines and professional practice all the time, is an important insight: the crisis of the nation-statebased system does not lead to a simple replacement of the international by an elusive global system of health governance. instead, it is the conviction that undergirds this article that certain re-territorializations are key to the reworking of health governance globally. leading science journalist laurie garrett wrote in her prescient betrayal of public trust ( : ) that "[s]afety . . . is as much a local as international issue. in public health terms every city is a 'sister city' with every other metropolis on earth". particularly "metropolitanization" is of great consequence as urban areas have been in the centre of re-emerging diseases such as sars and tb. on the basis of evidence from the sars outbreak in toronto, canada, we have argued in this article that more attention needs to be paid to the changing relationships of urban governance and (re-)emerging infectious disease. towards that end, we specifically looked at two dimensions of urban governance during the sars crisis. first, the way the legacy of the "bacteriological city" was reinterpreted in the sars crisis; second, the way in which the local health governance was embedded in a "post-westphalian" order of health governance. through reading these two dimensions against one another, we have discussed how urban governance-under potentially lasting conditions of the "new normal"-must face the new (or reemerging) challenge of dealing with infectious disease and that global health governance may be better off by taking the possibilities that lie in metropolitan governance more seriously. the toronto case study has revealed a rich casebook of evidence on how state institutions at various scales from the global to the localin constant interaction with civil society and economic actors-have shaped a new modus operandi in how to deal with infectious disease threats in a globalizing environment. not only have cities played a major role as sites and conduits of disease, they have also picked up their share of participating in new forms of governance that brings the (local) state back in. having said that, however, we also showed that both concepts-city and state-are becoming perforated as the "institutional void" around emerging infectious disease corrodes firm boundaries between jurisdictional responsibilities of territorial states and city regions. while sars pricked the skin of the global city system and showed the relative permeability of the westphalian nationstate order by germs, it reconfirmed a certain rigidity of borders (both external and internal) for human mobility. as global health governance made airports biopolitical switching stations and public health officials reverted to quarantine and other measures of sequestration, the state reaffirmed its power in no uncertain terms. as in the early days of the bacteriological city, when municipal administrations created a physical and social infrastructure of hygiene in the struggle against epidemics, urban governance gets assigned new responsibilities ranging from flu preparedness to surveillance once again. but the city is not what it used to be. in an age of heightened urban unboundedness our image of cities is recast "as nodes that gather flow and juxtapose diversity, as places of overlapping-but not necessarily connected-relational networks, as perforated entities with connections that stretch far back in time and space and resulting from all of this, as spatial formations of continuously changing composition, character and reach" (amin : ) . the new politics of place that amin sees on the horizon in this new world of perforated urban spaces now also has to take into account the politics of infectious disease we have discussed in this article. endnotes sars is caused by a coronavirus, which is assumed to have moved through zoonotic infection from civet cats in southern china to rural and urban human populations there, and subsequently to urban populations in several large, globalizing cities around the world, with beijing, guangzhou, hong kong, singapore and toronto among the ones that were affected most. in the canadian metropolis toronto sars claimed lives in two consecutive outbreaks, as people were confirmed infected cases, and thousands were quarantined. the economic fallout of the outbreak was tremendous as entire economic sectors-tourism, film, etc-suffered huge losses from which they have just begun to recover two years later (abraham ; fidler ; mclean et al ) . we have discussed these connections in greater detail in where we have brought foucault's work to bear on an analysis of racialization of the sars outbreak in toronto; see also sarasin (forthcoming) on this subject. this dialectics is different from but related to the one that gandy refers to when he points out the "devastating disparities between the mobility of capital and labour that condemn much of humanity to economic serfdom" which exist in the shadow of the "connections, networks and flows" which some see as characteristic of our current society (gandy a: - ) . defined as "the capacity of local officials to perform the core functions of public health": assessment, policy development, assurance (rodwin and gusmano : fn) "'westphalian' refers to the governance framework that defined international public health activities from the mid-nineteenth century" based on the political logic of sovereign nation-states that had come into existence after the years war (fidler : - ) . we are grateful to one of the reviewers who correctly pointed out that concentrations of disease in pre-industrial port cities had already led to internationally agreed-upon practices of disease control such as quarantine. we have reviewed this history in ali and keil (forthcoming). in canada, the healthcare system has long been seen as a major area of neoliberalization. we have seen the privatization of healthcare delivery that has potentially damaging effects on the model of social solidarity which underlies that country's medicare system. at the demand end of the neoliberalization and privatization of healthcare, individuals are now more likely to be held responsible for their health and to pay for services needed to address health issues. there is a large critical literature on this in the public domain, of which these are good examples: "canada needs a public health care system" (canadian dimension august ) and gindin et al ( ) . http://www.health.gov.on.ca/english/providers/program/pubhealth/sars/docs/new normal/dir bg .pdf, accessed february ). such measures were, for example, publicized widely on the website of the university health network, http://www.uhn.ca/home/sars/. cdc director warns sars, monkeypox are the "new normal", reported on wane-tv, http://www.wane.com/global/story.asp?s= , accessed february . she also was paraphrased as saying that "world travel has become common" that "anti-terrorism efforts have helped public health officials prepare for the infectious disease threat" and called "sars a very sobering reminder of the global community people share". geberding made similar comments on cbs television's early show on june , http://www.cbsnews.com/stories/ / / / earlyshow/health/health news/main .shtml, accessed february . "performativity" is inspired by the definition of "performance/name of action" proposed by bruno latour ( : ) , meaning that an "actor does not yet have an essence. it is defined only as a list of effects-or performances-in a laboratory. only later does one deduce from these performances a competence, that is, a substance that explains why the actor behaves as it does". mayor lastman was interviewed on cnn by aaron brown on april and displayed stunning ignorance of the who, its purpose and powers (the globe and mail :a ). a similar chain of events occurred when the ontario government, after making much noise about privatizing electricity supply and provision, stepped into the blackout crisis of august . after having lost all credibility earlier that year in questions of electricity, the ensuing crisis mode allowed premier ernie eves to appear on newspaper front pages as a strong leader who gets things done and problems under control. this section is based on boudreau et al (forthcoming), keil ( ) , keil and boudreau ( ) , keil and young (forthcoming) , kipfer and keil ( ) . our research in toronto benefited greatly from interviews with the following experts: bannerji a, toronto, march ; booth c, toronto, january ; finkelstein m, toronto, october ; gardam m, toronto, november ; low d, toronto, november ; macdonald v, toronto, september ; young j, toronto, december . d'cunha was removed from the position he held during the crisis because many considered his performance during the crisis as incompetent and insufficient. he was replaced on february by sheila basrur. for a comparative chinese perspective, see hongyi ( ). it must be noted, however, that canadians on the whole are less civil liberties conscious than most americans. collective necessity and public security often trumps concerns over individual freedoms in canada. whether it was the war measures act during the october crisis of the s when tanks rolled in montreal or in current public opinion about stricter security measures in the "war on terrorism", canadian pollsters have consistently found strong support for "stability and security" (clark ) . twenty-first century plague: the story of sars the urban geography of sars: paradoxes and dilemmas in toronto's health care homo sacer: sovereign power and bare life global cities and the spread of infectious disease: the case of severe acute respiratory syndrome (sars) in toronto ) pandemics, place, and planning: learning from sars regions unbound: towards a new politics of place rendering the world unsafe: "vulnerability" as western discourse sars: a local public health perspective new state spaces in canada: metropolitanization in montreal and toronto compared clement feared system may snap. the toronto star june:a braun b ( ) querying posthumanisms new state spaces: urban governance and the rescaling of statehood spaces of neoliberalism: urban restructuring in western europe and north america canadians want strict security, poll finds. the globe and mail city of plagues: disease, poverty and deviance in san francisco the sars experience in ontario, canada. presentation to ontario sars commission partnerships and participation: reconfiguring urban governance in different state contexts sars: political pathology of the first post-westphalian pathogen frankfurt: suhrkamp friedmann j ([ ] ) the world city hypothesis life without germs: contested episodes in the history of tuberculosis cyborg urbanization: complexity and monstrosity in the contemporary city deadly alliances: death, disease and the global politics of public health betrayal of trust: the collapse of global public health methodology problems in urban governance studies spaces of difference: reflections from toronto on multiculturalism, bourgeois urbanism and the possibility of radical urban politics the new normal: a sars diary the worldwide air transportation network: anomalous centrality, community structure, and cities' global roles geographical aspects of the emergence of infectious diseases policy without polity? 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hugh pennington on the sars virus the new public health: health and self in the age of risk. thousand oaks: sage pierre j ( ) comparative urban governance: uncovering complex causalities presentation at conference "invisible enemies the world cities project: rationale, organization, and design for comparison of megacity health systems powers of freedom: reframing political thought the new public health hegemony: response to severe acute respiratory syndrome (sars) in toronto re-placing the nation: an agenda for comparative urban politics public health and urban development: the plague in surat world city topologies looking back to look forward: reflections on urban regime analysis world city network: a global urban analysis power and decision-making in the city: political perspectives global health policy, local realities: the fallacy of the level playing field this research has been generously supported by a social sciences and humanities research council canada (sshrc) standard grant. we gratefully acknowledge the research assistance of claire major and sarah sanford. key: cord- -p hym o authors: landes, scott d.; turk, margaret a.; formica, margaret k.; mcdonald, katherine e.; stevens, j. dalton title: covid- outcomes among people with intellectual and developmental disability living in residential group homes in new york state date: - - journal: disabil health j doi: . /j.dhjo. . sha: doc_id: cord_uid: p hym o background: people with intellectual and developmental disabilities (idd) may be at higher risk of severe outcomes from covid- . objective: to describe covid- outcomes among people with idd living in residential groups homes in the state of new york and the general population of new york state. methods: data for people with idd are from a coalition of organizations providing over half of the residential services for the state of new york, and from the new york state department of health. analysis describes covid- case rates, case-fatality, and mortality among people with idd living in residential group homes and new york state through may , . results: people with idd living in residential group homes were at greater risk of severe covid- outcomes: case rates – , per , for people with idd compared to , for new york state; case-fatality – . % for people with idd compared to . % for new york state; and mortality rate – , per , for people with idd compared to per , for new york state. differences in cases and mortality rate were confirmed across regions of the state, but case-fatality rate was only higher for people with idd in and around the new york city region. conclusions: covid- appears to present a greater risk to people with idd, especially those living in congregate settings. a full understanding of the severity of this risk will not be possible until us states begin publicly sharing all relevant data they have on covid- outcomes among this population. there are an estimated . to million people with intellectual and developmental disabilities (idd) residing in community settings in the us. , idd is a lifelong disability that manifests before age and involves functional limitations in the areas of learning, language, and behavior. in the us, idd typically includes more common disabilities such as intellectual disability, cerebral palsy, and down syndrome, in addition to rare developmental disabilities, such as fragile x and prader-willi syndromes. people with idd face significant health disparities, with reports of high prevalence of cooccurring conditions, many of which are associated with more severe covid- outcomes. , this population is also underrepresented in health research, , a trend that appears to persist during the covid- pandemic. highlighting this silence, the cdc only issued covid- guidance relevant to this population in late may, four months after the first us case was reported. inadequate health surveillance of people with idd in the us has resulted in limited reporting on covid- outcomes for this. , to fill this gap in the literature, we recently analyzed a majority us sample of real-time medical records utilizing the trinetx platform, and found higher prevalence of respiratory, endocrine, and circulatory diseases among covid- patients with than without idd at all ages, and higher covid- case-fatality rates for patients with than without idd at ages - and - . there may be increased risk from covid- for individuals living in congregate care settings due to the challenges these types of residence present to physical distancing. [ ] [ ] [ ] this is particularly salient for people with idd, as it is estimated that % of adults with idd reside in congregate care settings, with shared use of essential living spaces (e.g., bedrooms, bathrooms, kitchens), close proximity to other residents, high levels of personal care assistance from staff, and multiple shift staffing patterns. researchers studying the well-being of people with idd recommend that all available data must be utilized to attempt to understand covid- outcomes among this population, and that analyses should attend to living situations, especially congregate care settings. , in this study, we describe covid- outcomes in a sample of people with idd living in residential group homes in the state of new york (us) and outcomes among the new york state population. our expectation is that covid- case rates, case-fatality, and mortality rates will be higher for people with idd living in residential group homes than for the general population in new york state. all data covers from the beginning of the pandemic through may , . data on people with idd living in residential group homes are from new york disability advocates (nyda), a coalition of organizations that serve and support individuals with idd in the state of new york. these homes typically have residents, but range from between and residents. three covid- outcomes were analyzed for this study: case rate, case-fatality, and mortality rate. case rate was computed as total number of positive covid- cases/population size. casefatality rate, a measure of the proportion of death among those who contract the disease (indicating disease severity) was computed as the total number of deaths/total number of cases. mortality rate, a measure of the rate of death from a disease among a total population (indicating burden of deaths due to a specific disease) was computed as total number of deaths/population size. all rates were computed for the state of new york overall, and for the economic regions within the state to account for the possibility of geographical variation, especially in light of the increased prevalence and transmission of covid- in and around the new york city region. we begin our analysis by describing the regional distribution of idd residential service providers and the new york state population. we then report and describe point estimates for all covid- rates with % confidence intervals among people with idd living in residential group homes, hereafter referred to as people with idd, and the general population of new york state, hereafter referred to as new york state. confidence intervals around point estimates were calculated assuming a standard normal distribution for new york state, and using wilson's score method for people with idd due to the smaller sample size. we utilized stata . (college station, tx) for all analysis. a description of the geographic distribution of number of residents/population, cases, and deaths among people with idd and new york state is provided in - table about here -covid- case-fatality and mortality rates are reported in table . the case-fatality and mortality rates were markedly higher for people with idd than for new york state across the entire state: . % compared to . % for case-fatality; , per , compared to per , for mortality rates. regional distinctions were apparent for both measures. in and around the new york city area, idd case-fatality (ranging from . % to . %) and mortality rates (ranging from , to , per , ) were higher than new york state case-fatality (ranging from . % to . %) and mortality rates (ranging from to per , ). for the regions outside of the new york city area, the case-fatality was slightly lower for people with idd ( . %) than for new york state ( . %), but the mortality rate remained higher for people with idd ( per , ) than new york state ( per , ). - table about here - covid- appears to present greater risk to people with idd, confirming results from our earlier study. results from this study clearly demonstrate that covid- case rates were substantially higher for people with idd living in residential group homes in the state of new city, long island, mid-hudson). the differences we observed in case rates between people with idd living in residentials settings and the new york state general population were more pronounced than the differences we observed in case-fatality. this means that while people with idd living in residential group homes in the state of new york have a much higher likelihood of being diagnosed with covid- , their risk of death once they are diagnosed, although comparatively higher than that of new york state, is not nearly as disproportionate. circumstances and decisions made early in the pandemic may have contributed to the higher case rate of people with idd living in residential group homes. those who tested positively for covid- or who had presumed infection (during the time of limited testing availability) were required to return to their residential setting, with instructions to sequester. lack of understanding about or attention to typical group home functioning (e.g., close quarters with limited ability to sequester, close personal assistance by many staff members, poor access to personal protection) may have resulted in the higher number of cases. though we cannot test this supposition, our assumption is that this higher number of cases did not result in similarly disproportional case-fatality because of, at least partially, if not fully, the efforts of multiple stakeholders -people with idd, their families, advocacy groups, residential providers, their staff, and healthcare providers -to ensure the best care possible for these individuals. in emerging pandemics, it is critical to de-aggregate data and examine outcomes for disparate outcomes. for people with idd, as well as other disability groups, the current pandemic reveals the need for public health surveillance systems to include disability status as a basic demographic characteristic. additionally, there is no active testing of all us citizens, other than within nursing homes. consequently there is no ability to determine infection-fatality rates in the larger us population. until a more comprehensive system is created, it is necessary to utilize all available data. , while the results from our study are informative, in order to have a complete picture of the possible differential effects of covid- on people with idd living in residential group homes, it is important to be able to analyze data for all individuals receiving services within each state and across the us. this will only be possible once states begin to publicly share their data on covid- outcomes for those with idd, as well as for other populations. opwdd has been collecting covid- data from residential group home providers since the middle part of march . yet, to date, this data has not been shared publicly. we are aware of one state, pennsylvania, that is publicly sharing some data on covid- outcomes among people with idd in residential group homes. the results from the previous study noting high case-fatality rates among people with idd, and this current study revealing disparate risk from covid- among people with idd residing in residential group homes reinforces that states should no longer keep this data private. there is an urgent need for all us states to publicly share all relevant data they have on covid- among people with idd receiving services in order to fully understand and address the risk that this pandemic poses to this population. the limitations to this study are primarily a result of states not sharing covid- data for people with idd. thus, we had to rely on data provided by a coalition of organizations that serve and support individuals with idd in the state of new york. although we commend nyda for their foresight and commitment to collecting data from their associated organizations representing over half of the people with idd living in new york state-certified residential group homes, the reporting is voluntary and some residential service providers in the state are not affiliated with nyda. as a result, we cannot be sure that the outcomes we observe in this study are representative of all people with idd living in new york state residential group homes. we suspect that the covid- outcomes for people with idd living in residential group homes on which we report in this study may be similar among individuals in other states. however, we cannot test this hypothesis. recently released data from the state of pennsylvania lends support for this supposition, reporting case-fatality rates for people with idd in residential group homes that are substantially higher than for the entire state. , we will not be able to test this hypothesis until data from other sources is available. the cases identified in our study most likely represent symptomatic cases. as a relatively high proportion of asymptomatic or mildly symptomatic covid- infections has been noted in some studies, it is important to recognize that, similar to many of the current studies of covid- outcomes, the reported case-fatality rates in this study may over-estimate the actual fatality rates. without knowledge of rates of asymptomatic testing among people with and without idd, we cannot determine whether the degree of over-estimation is similar or different for people with idd. currently, information is not available about the proportion of covid- infections that are asymptomatic or mildly symptomatic, so we are not able to estimate the infection-fatality rate. additional research that incorporates screening of asymptomatic people with and without idd would be needed to address this important question. other limitations of note are that we could not make statistical comparisons between the groups as we cannot guarantee exclusivity between the nyda data and nydoh data. also, since the u.s. department of health and human services did not require basic demographic information (age, biological sex, race-ethnicity) accompany all reporting of covid- positive cases until june , , we were not able to account for possible differences in the distribution of age, sex, and race-ethnicity in our analysis. results from this study demonstrate higher covid- case and morality rates for people with idd living in residential group homes across regions in the state of new york, and higher casefatality rate among those living in and around the new york city area. to address this increased risk, it is necessary to ensure that people with idd and those who provide for their care have access to preventive measures and the resources needed to carry them out (e.g., covid- information relevant and accessible to people with idd, adequate funding for staffing, access to personal protective equipment for group home residents and staff, testing when appropriate). in addition, healthcare providers must have the resources necessary to work effectively with people with idd (e.g., identify safe and effective strategies to include support providers when treating a patient with idd, use disability accessible communication strategies, not base allocation of medical services or goods rationing decisions on disability status). we urge all actors within the systems that support people with idd to take the necessary individual and systemic action to ensure their safety during this pandemic. we also encourage scientists to continue to explore the specific impact of covid- on people with idd and reduce the disproportionate risk of this population in the midst of the current pandemic. advocates have helped push authoritative sources to collect and share covid- data on other at-risk populations, including racial and ethnic minorities and individuals living in nursing homes, though that progress has been slow and uneven. in order for us to have a full accounting of covid- on the idd population, or other vulnerable populations, living in congregate settings, it is imperative that the entities that provide services for or monitor any segment of this population begin to openly share all relevant data they have on covid- outcomes among people with idd. continuum of intellectual disability: demographic evidence for the "forgotten generation prevalence of mental retardation and developmental disabilities: estimates from the trends in the prevalence of developmental disabilities in us children physical health of adults with intellectual and developmental disabilities preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease -united states intellectual and developmental disability and covid- case-fatality trends: trinetx analysis. disability and health journal improving public health requires inclusion of underrepresented populations in research persons with disabilities as an unrecognized health disparity population guidance for group homes for individuals with disabilities the public health response to the covid- pandemic for people with disabilities the covid- pandemic and people with disability state reporting of cases and deaths due to covid- in long-term care facilities. san francisco: kaiser family foundation structural vulnerability in the united states revealed in three waves of novel coronavirus disease (covid- ). the american journal of tropical medicine and hygiene. . . cdc. covid- guidance for shared or congregate housing the state of the states in developmental disabilities covid- guidance for shared or congregate housing new york state department of health. nysdoh covid- tracker two sided confidence intervals for the single proportion: comparison of seven methods pennsylvania department of human services. office of developmental programs (odp) covid- report pennsylvania department of health. covid- update a systematic review of asymptomatic infections with covid- ethics and health care in the covid- pandemic ( ) ( ) ( ) key: cord- -q ninzd authors: wang, a. q.; chan, edwin h.w.; yeung, stanley c.w.; han, j. b. title: urban fringe land use transitions in hong kong: from new towns to new development areas date: - - journal: procedia engineering doi: . /j.proeng. . . sha: doc_id: cord_uid: q ninzd abstract land in urban fringe area is the primary source for land supply and development. in hong kong (hk), nine new towns have been built in new territories since s, providing . km built-up land and large amount of residences for . million people. however, due to land scarcity, development restriction, and social opposition, new development area (nda), as the small-scale extension of new town (nt), was designated as one of the main approaches for hk medium and long term land supply. to demonstrate the characteristics of urban fringe land use transitions in hong kong, literature review and case study were used in this research. the history of new town development and the scheme of new development areas were introduced firstly. afterwards, the land use features of nt and nda were compared and the case of hung shui kiu nda was illustrated. it is concluded that while housing, infrastructure and facility were the main elements in nts, employment, vibrancy and environment were suggested to be the new compulsory elements in ndas integrated to the traditional planning concepts. as for the development approach, lease modification was adopted in nda to allow private landowners directly develop their land, in addition to the traditional development approach of land resumption in nt. it is suggested to ensure the development of nda, the proposed development plan should be persuasive to provide the optimal land use distribution as a trade-off among the profits of developers, the interests of local villager, government concern and the provision of land for future residents. also, community engagement will play a more important role in nda planning process. referring to the analysis of urban fringe land use transitions and strategies for planning and development, the study would also be helpful to others growing cities. land supply in hong kong (hk) has been highly concerned and discussed in a long term. due to its limited land according to " - policy address" [ ] , three features of ndas were identified. firstly, smaller scope in less than one fourth of the existing new towns such as tuen mun and sha tin; secondly, land supply for various uses such as housing, employment, high value-added and non-polluting industries; and thirdly, provision of quality living space and convenience to both residents and users. compared with the targets of houses, infrastructure and community facilities in nt, the nda contains more uses and sustainable planning concepts. however, few research concerned about nda and its difference from nt in hk. therefore, this study aims to illustrate how the nda was planned and to understand how land use was transited in the urban fringe of hk. background and literatures about nt development and the commencement of nda were reviewed. the characteristics regarding transition from nt to nda were then illustrated. the case of hung shui kiu nda was introduced to illustrate the planning process of nda and its differences from tin shui wai nt were compared. regarding the changing situation and new challenges, strategies for suburban land development in hk were discussed, which could also be helpful to others growing cities. achievements in new town programme were obvious. supported by essential infrastructure and community facilities, housing supply is the most greatest contribution made by nts, and public and private housing were provide for millions of people. it was suggested that policy direction, project management approach, planning standards, resource mobilisation, professional input, community support, as well as innovative ideas on design and construction technique contributed to rapid nt development. [ , ] the area, planned population, current population and planned population density [ ] were showed in table . however, some issues also appeared in nt development, since it attributed to large-scale immigrations and rehousing. at the beginning of nt construction, social consequences concerning the social integration of people who have been rehoused, the building of relationships and support networks among residents, the psycho-social adjustments of residents, the relationship between residents and the government, etc., were not well attended. [ ] spatially, mismatch between place of residence and place of work and polarization was observed, leading to whitecollar jobs concentrated in the older urban areas and blue-collar jobs in the newer towns. [ ] the inadequate provision of jobs and schools in new towns also resulted in widespread cross-district commuting between new towns and urban areas. [ ] in the study of tin shui wai new town, high unemployment rate and weakened social networks were figured out, indicating the shortages of resettling a high percentage of poor households in a single new town and the lack of access to a wider range of employment opportunities. [ ] even though the social and commuting challenges were confronted by nts, population dispersing from urban areas to the suburbs based on the transit-oriented development (tod) strategy gained favourable comments. [ ] related researches suggested that due to the comprehensive public transportation system and relatively limited use of private cars, the widespread commuting between new towns and urban areas does not lead to severe air pollution and fuel wastage. [ ] external transport links served by rail and road links to the urban area and adjacent districts created a sustainable community at the neighbourhood level, with potential for regional balance through alleviating spatial mismatch between nts and urban areas. [ ] regarding the ongoing enhancement of road links and employment, nts keep on adjusting to alleviate the persistent population pressure in hk and improve people's living quality. since the development of tung chung nt in late s, the concept of new town was seldom mentioned, which the basic information of the four ndas in hk was acquired from the official websites of nda studies [ , ] and showed in the following table. based on the planning and engineering studies, the outline development plan and layout plans will be proposed, in which the land was distributed for different uses. the land use structure reflected the function of the specific area. when developing the new towns, the main objective was to provide houses for increasing population, therefore the industrial zones were extracted from the ozps [ ] , and the percentage of these seven land use categories were calculated. in figure , the built-up land structure of the nts and ndas were illustrated. it shows that in nts, the percentages of residential land were much more than those in ndas, while the percentage of open space and other specified uses were relatively less ndas. for example, in tws nt nearly % percent built-up area was for residential use, while in hsk nda the percentage of residential land was less than %, reduced by about a half. in regarding the planning issues appeared in nts, such as the employment unavailability and high residence density, the ndas are like kinds of remediation to make up these shortages to improve the regional planning and development function. since the nts were dominant for residence, more industrial development were considered in ndas, and the living environment were emphasised in new development, with the provision of more open spaces as an important symbol. in new town development, land resumption is an essential and the only approach to obtain the development right, so that the government could sale the land and ensure land supply. there are restrict regulations for land resumption, guiding the resumption process and providing compensation standards. however, another approach for obtaining development right was proposed in the recent planned ndas, which is lease modification. referring to some privately owned land, private land owners in new towns were allowed in the past to modify land leases for private developments, while the government was no longer involved in this process, neither resuming nor selling land. the implementation of this lease modification approach was attributed to opposition from some pan-democratic legislative council members who thought the compulsory resumption of private land would deprive the rights of landowners to develop the land on their own. [ ] in the study of ktn and fln nda, the two approaches were both adopted, namely the enhanced conventional new town approach. it is said that "private land will be resumed for development according to planned uses, while flexibility will be provided for private landowners to apply for lease modification (including in-situ land exchange) to develop their land planned for private development in the two new development areas". [ ] a set of criteria with specified deadlines of lease modification application should be met to get approval. this is to ensure that such applications will comply with the planning and timetable for the ndas development. on this front, the government will impose more stringent requirements in processing applications for modification of lease subject to specified criteria. the criteria include stipulating that only sites planned for private development are eligible for the lease modification applications. the applications must comply with specific guidelines and conditions to ensure comprehensive planning, and time limits will be stipulated for completion of such applications to ensure timely provision of housing and other facilities. the land owners must also offer fair treatment to tenants/occupants, including providing a monetary compensation comparable to the government's arrangement. [ ] this combined approach aims to protect private development right without compromising the planning intention and timely land supply. the ownerships of current development area, which were much more scattered and complex than the land in previous nts, may be the reason for adopting lease modification approach. if compulsory resumption was carried out, it is not easy for so many land owners to take out their lands to government. it may also save the negotiating time to landowners who initially opposed the land resumption and were afraid to lose their landownerships. in the meanwhile, financial expenditure of land resumption would be reduced for government. however, although this approach protected landowners' rights, it was also opposed by some citizens regarding its potential damage to villagers' rights. because most of the private land were not owned by local villagers but already bought by different private developers through contracts in the last few decades. even the villagers still live there, their landownerships were transited to the developers. since government would not resume the land, it is the private developers' responsibility to compensate the villagers, whose interests may not be guaranteed when negotiating with developers. the issues in both land resumption and lease modification were discussed, and whether to continue with conventional public oriented resumption or private participation is still suspending. a few applications of lease modification were under consideration in ktn and fln cases, but haven't got the result yet. [ ] this approach will also be adopted in the development of hsk nda. the fact is that compared with nt development, it is more difficult for the government to acquire large piece of land to develop, due to the scattered land ownerships, more complicated relationships among government, different private land developers, and local villagers, as well as the different public opinions and interests to take into consideration in the planning and development process of nda. in addition to the built-up land structures and the development approaches, some planning concepts were also modified or paid attention in ndas. two main concepts, community vibrancy and nature, were highlighted in this section. vibrancy is related to facility and service accessibility as well as social integration, while nature is related to ecological protection and the improvement of living environment. the high density of residence in nts triggered some social issues. the lack of street life in the pedestrian network both within and in between these neighbourhoods discouraged social activities and interaction. the recent growing demand on the preservation or revitalization of street life has been echoed. in the planning of ndas, the mixture of residential and commercial uses as well as multi-function open spaces were suggested. for example, in the ozps of fln and ktn, commercial uses are allowed in some of the residential sites to serve the local community, therefore shopping street and continuous shop frontages will be provided in residential zones. pedestrian shopping streets were formed by terraced podium with open space corridors, providing commercial and leisure facilities such as café, restaurants and retail shops on the side. additionally, integration of new and old communities, vibrant activity node around the railway station and a balanced population profile with a mix of public and subsidized housing and various types of private housing was also lined out in the plans, to enhance vibrancy and encourage social integration. [ ] environmental sustainability has been paid more and more attention in recent development plans. the land use zones of "agricultural" which was rarely mentioned in nt plans, were designated in the ozps of fln and ktn ndas. it aimed to retain and safeguard fallow arable land with good potential for rehabilitation. in hk, the transportation is related to both vibrancy and environment. in addition to compact city form and population concentration near the public transport interchanges, comprehensive pedestrian and cycle traffic networks will be provided to minimize road traffic and improve regional accessibility. environmental friendly transportation system was proposed in ozps. in addition to pedestrian and cycle lane, electric bus may be operated to provide feeder services from the area to railway stations. compared with nt development in the last few decades, in nda development, peoples' needs could not be satisfied with residence and infrastructure only, but to live more comfortably with social harmony and better environment. to better illustrate the differences between nt and nda, the cases of tsw and hsk were compared. hung shui kiu located in the west new territory, next to tin shui wai new town. it will not only provide housing and other land supply in hk, but also serve as a "regional economic and civic hub" for north west new territory. [ ] and showed in figure . were summarized in six aspects: commercial nodes, industry, social integration, transport, facility and environment. identified items were showed in table . according to the planning changes showed in the above table, it evidently implied that the nda was no longer restricted to the housing-oriented town, but a comprehensive development area, with diversified functions of commercial services, industrial concentration, integrated communities, convenient and environmental friendly transportation, social services, recreation, leisure, etc. although hsk was regarded as an extension of tsw nt, its development objectives and potential attraction seemed much stronger than tsw. table compared the main planning information in tsw and hsk. the information were collected from their development plans [ , ] . [ ] different land use structure and function, development approaches, and planning concepts between nt and nda were demonstrated in this table. since nda was an extension of its closest nt, their difference, especially the land use functions would be interacted with each other, while the regional attractiveness and development vitality were improved with their integration. since nts were already constructed or under expansion, the new town programme in the last decades considerably contributed to the economic and social development of hk. the flowing question is, will we have the tenth nt? the most important issue to concern is whether the government could find out a large piece of land for developing. however, regarding the high density in hong kong island and kowloon, as well as the complex land ownership in suburban and rural new territories, it is hard to develop a new town in traditional way. as the city expanding, the development strategies would also be changed to adapt current situation, including the complicated ownership, peoples' increasing needs and environmental issues. development in suburban area is still an important approach to provide land for urban use, however, more challenges would be confronted by governments and urban planners. whether private developers could/could not develop their land directly without land resumption is an important criteria to identify new/conventional development. regarding the scattered land ownership and difficulties in acquire the large piece of land to develop, the lease modification approach intended to encourage landowners to provide the land as planned intentions, assuring their ownership would not be lost. however, in some peoples' opinion, this approach is more likely to protect developers' development right and increase their interests, rather than protect local villagers' rights. as for the government, it is essential to trade off among the profits of developers, the interests of local villager, and the provision of land for future residents. no matter what development approaches were implemented, the baseline is the outline zoning plan, which means all development should be consistent with the planning uses. therefore, more involvements were required in the planning phase, and the in advanced understanding of the interests of developers, local villagers and future residents were essential. if the ozp is persuasive enough to provide the optimal land use distribution regarding opinions from all affected stakeholders, it would become the balanced decision based on the trade-off of different peoples' interests to guarantee the development, whatever the development approach is. the changing planning concepts and elements were also distinct. if housing, infrastructure and facility were the main elements in nts, employment, vibrancy and environment were suggested to be the new compulsory elements in ndas integrating to the traditional planning concepts. rather than providing houses for people to live, the better living quality and environment should be considered in new development. economic and civic hub, commercial node, retail clusters, street vibrancy, logistics, enterprise quarter, riverside promenade, regional town park, plaza, amenity strips, community gardens, heritage trails, visual corridors, and even fung shui lanes will be parts of suburban planning to satisfy peoples' needs in new development projects. new town development is the dominant land supply approach in the urban fringe of hong kong in th century, which contributed considerably to economic development and the housing, infrastructure and facilities provision for the increased population. however, it was more and more difficult to acquire large pieces of land for new towns, and nda was designated as the new approach to continually supply built-up land in urban fringe area. the land use transition from nt to nda were embodied in three aspects, including land use structure and function, development approach, and planning concepts. rather than the main function of residential land supply in nt, commercial, industrial and mixed uses were also considered to achieve various urban functions in the area. regarding the scattered and complicated land ownership, private landowners were able to directly develop their land through lease modification in nda, as an alternative development approach of land resumption in nt. in addition, vibrancy and nature became two essential planning concepts in nda for more sustainable development. since nda was an extension of its closest nt, nda could make up the functions that were absent in nt, and their interaction would improve regional attractiveness and vitality in urban fringe area. confronting the challenges in nda, the planning process and public engagement are more important than nt. the proposed layout plan should be persuasive enough to provide the optimal land use distribution based on opinions from all affected stakeholders, as a balanced decision and trade-off of different peoples' interests. in addition to the case of hk, the understanding of land use transition in urban fringe area and strategies for development challenges would also be helpful to others growing cities. the government of the hong kong special administrative region new towns, new development areas and urban developments the government of the hong kong special administrative region proceedings of the institution of civil engineers hong kong new town development, hkie transactions the development of new towns in hong kong and singapore: some social consequences spatial economic impacts of new town development in hong kong: a gis-based shift-share analysis generating urban lifestyle: the case of hong kong new-town design and local travel behaviour the influence of suburbanization on the access to employment of workers in the new towns: a case study of transport sustainability and residents' perceived sustainability: a case study of transit-oriented development in hong kong a study of commuting patterns of new town residents in hong kong planning vision and strategy kwu tung north/fanling north new development areas hung shui kiu new development area planning and engineering study town planning board, statutory planning portal enhanced conventional new town approach the government of the hong kong special administrative region, result of north east new territories new development areas planning and engineering study this paper is prepared with the support of research fund from hong kong rgc grant of the hong kong polytechnic university. key: cord- -u r oh z authors: bian, hongfen; xu, fei; jia, yumin; wang, lei; deng, shengchao; jia, aiqing; tang, yong title: a new immunochromatographic assay for on-site detection of porcine epidemic diarrhea virus based on monoclonal antibodies prepared by using cell surface fluorescence immunosorbent assay date: - - journal: bmc vet res doi: . /s - - - sha: doc_id: cord_uid: u r oh z background: porcine epidemic diarrhea virus (pedv) is a highly effective pathogen that can cause death of new-born piglet, resulting in big economical loss in pig farming industry. for rapid detection of pedv, a new immunochromatographic assay (ica) based on monoclonal antibodies (mabs) was developed in this study. results: the mabs were prepared by using pedv positive hybridoma cells that were selected by using cell surface fluorescence immunosorbent assay (csfia). fourteen mabs against pedv strain isolated from south of china were prepared. the optimal mab a was coated on nc membrane as the capturing reagent and the mab a h was coupled to gold nanoparticles (aunps) as detection reagent for the new ica. the new ica was used to measure pedv in phosphate buffer containing tween- . results indicated that the limit of detection (lod) of the new ica was . μg/ml ( . × ( ) tcid( )/ml) and the liner detection range of the ica was . – μg/ml ( . × ( )– ( ) tcid( )/ml). the specificity analysis results showed that this new ica had no cross reaction in the presence of other porcine viruses. the ica was also validated for the detection of pedv in swine stool samples with little interference from swine stool. to compare its accuracy to other traditional detection methods, swine stool samples from south of china were investigated with the new developed ica, commercial strip and rt-pcr. results showed that the new ica was more comparable to rt-pcr than commercial test strip. conclusions: a new ica based on mabs prepared by csfia was developed in this study. it was a sensitive, specific and rapid method that could be used for on-site detection of pedv and therefore was useful for the diagnosis and prevention of ped. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. porcine epidemic diarrhea virus (pedv), which belongs to the genus alphacoronavirus and the family coronaviridae, is an enveloped single-stranded positive-sense rna virus [ , ] . pedv is a highly effective pathogen responsible for causing porcine epidemic diarrhea (ped), a disease characterized by severe and acute watery diarrhea, dehydration and vomiting that results in high mortality rate of one-week-old piglets [ , ] . since the first appearance in england in the early s, outbreaks of ped have been reported in several european and asian countries [ , ] . ped was first reported in china in , followed by a large-scale outbreak of ped in december that led to heavy economic loss [ , ] . therefore, it is of great importance to properly and routinely monitor pedv. unfortunately, due to the fact that pedv and a different alphacoronavirus, transmissible gastroenteritis virus (tgev), have the same epidemiological and clinical features. these two viruses have led to complications in clinical diagnosis. therefore, it is of great importance to develop differential laboratory tests [ , ] . to date, several methods including rt-pcr [ ] , separation identification [ ] , serological method [ ] , enzyme-linked immunosorbent assay (elisa) [ ] and colloidal gold method [ ] [ ] [ ] have been used to detect the pedv antigen. although rt-pcr serves as a good standard due to its high sensitivity and accuracy, this method relies heavily on sophisticated equipment and expensive apparatus. several other common methods are also not suitable for on-site diagnosis due to the following reasons. separation identification means to isolate pedv in vero cell cultures from the small intestine of a pedv infected piglet. it is a classical method for pedv detection, but it is time-consuming for it needs at least one week. the serological method can only detect pedv antibody. however, whether the pedv antibody is from vaccine infection or wild infection is still unknown. elisa is a cheap and simple approach for pedv detection, however, it involves long incubation period, multiple washing steps, and the assistance of a microplate reader. in contrast, recently developed immunochromatographic assay (ica) is much more applicable for on-site diagnosis of pedv for it is simple, sensitive, specific and can be operated without training. therefore, this method could be useful for monitoring the infection of ped [ ] [ ] [ ] . currently, the most widely used commercial pedv test strip in china (bionote test strip), which is made by utilizing ica, is based on the pedv-dr strain. the strain was harvested from a suspension of minced small intestine from infected neonatal pigs in south of korea [ ] . considering regional differences in strains, it might not be the best choice for pedv detection in south of china. a pedv strain chyj was isolated from the fecal specimen of a -day-old dead piglet in march on a commercial swine farm in guangdong province in the south of china [ ] . in this study, we prepared monoclonal antibodies (mabs) using cell surface fluorescence immunosorbent assay (csfia) [ ] , a simple and rapid method for selecting positive hybridoma cells. fourteen mabs against this pedv strain were prepared. relying on signals emitted from gold nanoparticles labeled mab (aunps-mab), a new ica was developed for sensitive, specific and on-site detection of pedv in swine stool in china. a comparison between rt-pcr, bionote test strip and the ica was performed to confirm the applicability of the newly developed ica for on-site pedv detection. vero cell, porcine epidemic diarrhea virus (pedv) strain named chyj , pseudorabies virus (prv), classical swine fever virus (csfv), transmissible gastroenteritis virus (tgev) and swine stool were obtained from guangdong haid institute of animal husbandry & veterinary (guangdong, china). porcine reproductive and respiratory syndrome virus (prrsv) and porcine circovirus- (pcv- ) were obtained from winsun bio (guangdong, china). balb/c mice were purchased from southern medical university. myeloma cells (sp / ) were purchased from shanghai cell biology (shanghai, china). gibicorpmi- was purchased from asegene (guangzhou, china). ninety-six-well polystyrene plates were purchased from jet biofil (guangzhou, china). goat anti-mouse igg h&l (hrp) was purchased from abcam (cambridge, ma). mab subtype classification kit was purchased from sigma (usa). the hrp-labeling kit was purchased from galaxy-bio (beijing, china). bca kit was purchased from thermo (usa). nitrocellulose (nc) membrane (hf s ), conjugate pad, sample pad, plastic backing and absorbent pad were purchased from millipore (shanghai, china). pedv ag test kit was obtained from bionote (korea). ultrapure water produced by a milli-q ultra pure system (millipore, usa) was used throughout this study. all chemicals used were of analytical grade or higher. absorbance of the hrp-based elisa was measured using a synergy h hybrid multi-mode microplate reader (bio--tek instruments, inc., winooski, vt). the following equipments were also utilized in this study: centrifuge r (eppendort, germany), xw- avortex mixers (shanghai, china), magnetic stirrer (beike, beijing), dynabeads mx mixer (invitrogen, america), programmable strip cutter hgs (autokun, china), xyz platform (bio-dot scientific equipment, china), and electrothermal forced air convection drying oven (taisite instrument, china). pedv was inoculated onto a vero cell monolayer for min at °c. cell infection at a moi of . . then maintenance medium was added and cultured for or days. when the cytopathic changes reached above %, the cells were collected and repeatedly frozen and thawed for times. after ultrasonic cracking and centrifugation at rpm for h, the supernatant was further centrifuged at rpm for h and the precipitate was resuspended in pbs ( . m, ph . ). the crude extraction virus was successively added into %~ % sucrose-pbs and centrifuged at rpm for h. then it was resuspended in pbs and centrifuged at rpm for h to remove sucrose content. the purified virus was resuspended in pbs. the uninoculated vero cells were subjected to the same treatment and used as negative control. the pre-purification protein concentration was measured by nanodrop micro nucleic acid tester. virus titer was expressed as tcid , tcid /ml. viral protein concentration was measured using bca, μg/ml. . ml of the purified pedv antigen and an equal volume of freund's complete adjuvant, was injected into each mouse ( weeks, female, balb/c) for the first immunization. mice were immunized every weeks. tail blood was taken on the tenth day after the third immunization. mice with high titer were selected for fusion days after they were boosted with immune antigen pedv. to prepare the hybridomas, the mice were euthanized by cervical dislocation. all the mice were sent to huaqiao hospital for centralized treatment after the study. csfia, a simple and rapid method for selecting positive hybridoma cells, was used to screen for positive hybridoma cell clones. in this study, pedv antigens were first anchored to the hybridoma cell surface through a dual functioning molecular oleyl-peg -nhs. specific antibodies secreted from hybridoma cells were then captured by the antigens on the cell surface. positive hybridoma cells were stained using a fluorescently labeled anti-mouse igg-fc antibody (fig. ) . after the addition of a methylcellulose semisolid medium, positive clones were picked using a pipet. these positive cell clones were used to produce monoclonal antibodies after direct expansion [ ] . mabs were prepared by inducing ascites in mice. they were then purified by ammonium sulphate, desalt column, and protein g affinity chromatography column. mabs were preserved at − °c after freeze-drying. titer of mabs was determined by indirect elisa with pedv as coating antigen and hrp-goat anti-mouse igg as secondary antibody. the sensitivity of mabs was determined by indirect competition elisa with pedv as coating antigen and pedv specific hrp-monoclonal antibody as the competitors. the mab classification kit was used to identify the category and subclass of immunoglubulin. the mab pair for pedv detection was selected by double antibody sandwich elisa matrix fig. the mechanism of csfia based on the specific binding of antigens anchored on the positive hybridoma cell surface and capturing of secreted antibodies from the same cells method with hrp labeled mabs as secondary antibodies and mabs as coating substrates. the preparation of gold nanoparticles (aunps) and gold nanoparticles labeled mab (aunps-mab) to prepare aunps, trisodium citrate dehydrate was used to reduce gold chloride (haucl ). in brief, ml ultrapure water was added to a clean triangle flask and heated and stirred on a magnetic stirrer until boil. then, ml of % haucl was quickly added to the triangle flask and . ml trisodium citrate dihydrate ( mg/ml) was added after a few seconds. the solution was heated for min, and then moved to an unheated plate for continued stirring. the prepared aunps were then diluted with ultrapure water to ml. aunps-mab was prepared by labeling mab to aunps. first, ml of aunps ( . mg/ml) was added to a clean centrifuge tube, and μl of . m k co were added; the solution was mixed on an avortex mixers. then, μl mab was quickly added to the centrifuge tube with mixing. the mixture was rotated for min and then kept still for min at room temperature. subsequently, μl of % bsa were added to cover the unconjugated site. the mixture was rotated for another min and then kept still for min at room temperature. finally, the mixture was centrifuged at rcf for min and the precipitate was resuspended in μl pbs ( . m, ph . , containing % (w/v) sucrose, % (w/v) trehalose, . % (w/v) pvp k , . % (w/v) s- , % (w/v) bsa, and . % (w/v) tween- ). this new ica was sandwich type, in which two monoclonal antibodies were used separately as capture and detecting reagents to detect pedv (fig. ) . gray value corresponding to signal from the red t-line was obtained using image j [ ] [ ] [ ] . the assembly of the new ica was as follows: the new ica was made of pvc plate, nc membrane, sample pad, conjugate pad and absorbent pad. pbs ( . m, ph . ) diluted mab ( . mg/ml) and goat anti-mouse igg ( mg/ml) were dispensed on specific areas of nc membrane called the test line (t-line) and calibration line (c-line) using an automatic dispenser at a volume of μl/cm. the nc membrane was dried at °c and saved for later use. the aunps-mab was loaded onto the conjugate pad using an automatic dispense system set to . μl/cm and then dried at °c. the pretreatment of sample pad involved soaking in pbs ( . m, ph . , containing . % (w/v) sucrose, % (w/v) bsa, and % (w/v) tween- ) and drying at room temperature and then at °c. the pvc plate acted as the holder of the new ica, onto which sample pad, conjugate pad, nc membrane and absorbent pad were pasted with an overlap of mm between each part. after the assembly was completed, the new ica was cut into . -mm-wide and -mm-long strips using a programmable hgs strip cutter and kept in a suitable plastic cassette for further use. a fully assembled new ica is shown in fig. a . to optimize the quality of the new ica, some important single factors were optimized. they were capture and detection mab, the size of gold nanoparticles, the type of sample pad, the type of conjugate pad, the type of nitrocellulose membrane, the type of absorbent pad, the amount of tween- addition and the spray volume of aunps-mab. the optimization methods are shown in the supplemental materials. to verify the specificity of the new ica, pedv, prv, pcv- , prrsv, csfv, and tgev at the same concentrations were prepared and tested following similar procedures. the stability of the new ica was tested by comparing results from the experiments performed now to those from experiments performed a month later using the same icas. for the detection of pedv in spiked samples, negative samples with different pedv concentrations were prepared. first, μl pb ( . m, ph . , containing % (w/v) tween- ) was added to a . ml centrifuge tube. then, μl negative swine stool a was added to the solution and mixed for min. after centrifugation at rcf for min, the solution was kept still for min. the supernatant was collected and the precipitate was discarded. pedv was incorporated into the sample at . , , , and μg/ml. finally, μl of the spiked solutions were added to the sample holes of the new icas respectively. photos were taken to record the results after min of reaction. for detection of pedv in swine stool samples, μl of swine stool samples and μl of pb ( . m, ph . , containing % (w/v) tween- ) were mixed and incubated for min. after centrifugation at rcf for min, the solution was kept still for min. the supernatant was collected and the precipitate was discarded. the swine stool samples were analyzed using rt-pcr, bio-note test strips and the new ica, respectively. preparation and characterization of antibody to pedv cell lesion was above % after pedv was inoculated onto vero cell monolayer for h. after repeated freezing and thawing, cracking and sucrose-pbs gradient centrifugation, the virus bands between the and % interface were collected. after identification, protein concentration was determined to be mg/ml. the prepared pedv was used to immunize mice to generate mabs against pedv [ ] . from the hybridoma cells generated against pedv, clones that could produce mabs with strong pedv binding ability were selected. immunoglobulin isotyping suggested these clones were igg a. to select pedv mab pairs with high sensitivity and specificity, a double antibody sandwich elisa was used. the amount of capture antibody for coating and detecting antibody in both experimental and control group was μg/ml. μg/ml pedv was added to each well of experimental group while an equal volume of pbs was added to the control group. only the mab pairs which have strong signal (od ≥ . ) in pedv group and no obvious signal (od ≤ . ) in pbs group were marked as positive. all the mab pairs which have no strong signal in pedv group or have obvious signal in pbs group were marked as negative. as shown in tables , of the mabs were successfully paired using double antibody sandwich elisa matrix method. these successfully paired mabs ( a , h , a , a h and h ) were used in the new ica for their outstanding binding ability. first, the new ica was optimized by selecting the best pair from the selected mabs. the optimization results showed that a was the best capturing mab and a h was the best detection mab (see additiona file : figure s . in the supporting information, number represent a as capturing mab and a h as detection mab). in addition, since gold nanoparticles of suitable size is essential to a successful ica, an assay was performed to optimize the size of gold nanoparticles. in brief, nm, nm, nm and nm aunps were used to label mab a h . with increasing size of gold nanoparticles, the red signal of the t-line also increased, while the red signal of the c-line remained the same (see additional file : figure s . in the supporting information). in addition, the reaction was not blocked at any time during the process despite the increasing size of the gold nanoparticles. we found that aunps of nm was associated with the strongest red signal at the t-line with to no impairment to the reaction process. therefore, nm was chosen as the optimized size for aunps for subsequent experiments (see additional file : figure s . in the supporting information). interestingly, the type of sample pad, conjugate pad, nc membrane and absorbent pad also appeared to have great impact on reaction rate of the new ica. to optimize these factors of the ica, different types of sample pad, conjugate pad, nc membrane and absorbent pad were tested in the optimization experiment. as shown in additional file : figure s . in the supporting materials, the new ica with gl-b as sample pad showed the most uniform red c line without any break. therefore, gl-b was chosen as the optimized sample pad. it can be seen from additional file : figure s . in the supporting materials, the new ica with polyester film as conjugate pad showed the most uniform red c line without any break. thus, polyester film was selected as the optimized conjugate pad. what can be learned from additional file : figure s . was that the new ica with millipore as nc membrane showed the most uniform red c line without any break. therefore, millipore was chosen as the optimized nc membrane. as for the optimization of absorbent pad, the new ica with h as absorbent pad (see additional file : figure s . in the supporting materials) showed strong color signal at the t-line. therefore, h was chosen as the optimal absorbent pad for the new ica. as tween- can remove unbound aunps-mab on the t-line and reduce nonspecific binding. sample solutions with different volumes of tween- ( , , , and μl/ml) were added to icas. results confirmed that no red line on the t-line was observed in the negative sample. at μl/ml upward, stronger red color at the t line of negative sample was observed with increasing volume of tween- added (see additional file : figure s . in supporting information). results for positive sample remained almost the same with increasing volume of tween- . therefore, μl of tween- to ml of sample solution was chosen as the optimized ratio for subsequent experiments. furthermore, the spray volume of aunps-mab was also important to the new ica. as shown in additional file : figure s . in supporting information, no red line at the t-line of the negative sample ica was observed until the spray volume of aunps-mab was at μl/cm and the red color on the t-line of the negative sample ica was more intense with increasing spray volume. however, the red line at the t-line of positive sample test strip remained almost the same. taking nonspecific adsorption and sensitivity into consideration, μl/cm was chosen as the optimal spray volume for subsequent experiments. the new ica was designed for efficient detection of pedv. the performance of the new ica for detecting pedv at various concentrations was tested using a serial dilution of pedv in pbt ( , . , . , . , and μg/ml) under the optimized condition (fig. a) . the limit of detection (lod) was found to be . μg/ml ( . × tcid /ml). to quantitatively analyze the performance of the new ica, gray values obtained from image j were used to draw a standard curve in origin . (fig. b) . the liner detection table the selection results of paired antibodies in double antibody sandwich elisa capture antibody a h h d a e c h h g h a g c f c f detection antibody hrp-a h ---++ ---------- range was . μg/ml to μg/ml ( . × to tcid /ml) and the coefficient (r ) was . . the exact value of pedv concentration could be read directly by comparing results and the photos corresponding to the standard curve. these results indicated that this new ica could determine pedv in a precise and quantitative manner. to confirm the specificity of the new ica, kinds of swine viruses were tested and pedv was used as positive control. these swine viruses were assayed by the new ica at the same concentrations as pedv. the red line at the t-line was obvious in pedv sample, while it was invisible in samples containing other swine viruses (fig. a) . these results indicated high specificity of the new ica. results were further analyzed using gradation histogram made by origin . based on gray values obtained from image j. no significant cross-reaction of other swine viruses was observed in the developed new ica (fig. b) , which further confirmed its high specificity. to verify the stability of the new ica, experiments were carried out at different time points using the same ica and pedv. in both experiments, the positive sample solution showed a red line at t-line while the negative sample solution did not (see additional file : figure s . in the supporting information). these results indicated that the new ica was stable over time. negative swine stool was mixed with pedv to prepare the spiked samples in this study. spiked samples that included . , , , , or μl pedv were tested. the red color at the t-line became more intense with increasing pedv concentration. each spiked sample was analyzed in six repeated experiments and the gray values were calculated using the standard equation corresponding to the standard curve. as shown in table , the recoveries of the new ica ranged from to . % with the highest relative standard deviation (rsd) calculated to be . %. the result indicated that the new ica was ideal for detection of pedv in spiked samples. to analyze the performance of the new ica in detecting pedv in swine stool samples, swine stool samples were collected from different swine farms from south of china. rt-pcr, commercial bionote test strip and the new ica were used to test these swine stool samples, respectively. as shown in table , the total coincidence of bio-note test strip to rt-pcr was . % while that to the new ica was . %, indicating that the new ica was more accurate than bionote test strip. in the present study, an immunochromatographic assay for pedv detection was developed and tested with spiked samples and swim stool samples from field infected pigs. the assay was based on mabs to chyj , which is a new strain of pedv found in south of china and therefore is an appropriate target antigen for pedv detection. first, to prepare pedv specific monoclonal antibody, immune antigen pedv was cultured and purified in the normal way to ensure the quality of immune effect. t he well prepared pedv mabs were used to do a double antibody sandwich elisa matrix, in which these mabs were used as capture antibody and the same mabs labeled with hrp were used as detection antibody. the aim was to find which mab as capture antibody and which hrp-mab as detection antibody can produce the best detection result. that means, which mab pair had the best binding ability to pedv. results showed that a , h , a , a h and h were these mabs that can pair successfully. second, due to the fact that the paired antibodies selected by double antibody sandwich elisa matrix may not be suitable for the new ica due to the differences in materials and environment, the new ica was optimized by selecting the best pair from the selected mabs. a was proved to be the best capturing mab while a h was the best detection mab. this optimization experiment greatly improved the sensitivity of the new ica. third, gold nanoparticles were important for a successful ica. if they were too big, they would block nc membrane and weaken red signal of t and c line. on the other hand, if too small, the red signal of t and c line was weak and it was not easy to observe it. considering both, the aunps of nm were found to be the optimal aunps in this study. the spray volume of aunps-mab was also optimized. if the spray volume was too high, it was easy to produce nonspecific adsorption. however, if it was too low, the result would have low sensitivity. μl/cm was selected considering both sides. forth, different types of sample pad, conjugate pad, nc membrane and absorbent pad had different influences on running speed, releasing amount and nonspecific absorption. so they were optimized. results showed that the optimized condition was gl-b as sample pad, polyester film as conjugate pad, millipore as nc membrane and h as absorbent pad. fifth, tween- in sample solution acted as surface active agent, which can accelerate running speed. a high running speed may be not good because it can reduce sensitivity. therefore, the tween- concentration was optimized and results showed that μl of tween- added to ml of sample solution was the best choice. specific experiment showed that there was no cross reaction between this ica and other swine viruses, indicating that this ica can distinguish pedv from other swine viruses. when detecting pedv in pbt, the lod was . μg/ml ( . × tcid /ml) and the liner detection range was . - μg/ml ( . × - tcid /ml). the pedv concentration in cultured pedv was pretty high. therefore, it can be used to detect cultured pedv. the data obtained by the new ica were compared with those obtained by both rt-pcr and commercial strip. it has been described that rt-pcr is the most sensitive and trustworthy method for pedv detection. in this study, the commercial strip was included for comparison purpose. the data analyzed in the present work showed that the total coincidence of bionote test strip to rt-pcr was . % while that to the new ica was . %, indicating that the new ica was more comparable to rt-pcr than commercial test strip. these results suggested that the new ica was suitable for monitoring pedv. the new ics shows pretty good detection ability of detecting pedv in swine stools, which will help pig farms in diagnosis of pedv. based on the success of making this new ics, double pathogen detection is going to be done. it can satisfy the need of pig farm. in addition, pedv fluorescent test strips will be done for precise quantitative detection. we believe that these new icas will bring great help to agriculture. coronavirus genome structure and replication further analysis of the genome of porcine epidemic diarrhoea virus porcine epidemic diarrhoea virus: a comprehensive review of molecular epidemiology, diagnosis, and vaccines porcine epidemic diarrhoea virus as a cause of persistent diarrhoea in a 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virus detection in faeces development of rapid immunochromatographic strip test for the detection of porcine epidemic diarrhoea virus reverse transcription crosspriming amplification-nucleic acid test strip for rapid detection of porcine epidemic diarrhea virus a novel diagnostic approach to detecting porcine epidemic diarrhea virus: the lateral immunochromatography assay triple lines gold nanoparticle-based lateral flow assay for enhanced and simultaneous detection of leishmania dna and endogenous control microchip based and immunochromatographic strip assays for the visual detection of interleukin- and of tumor necrosis factor alpha using gold nanoparticles as labels multicolor immunochromatographic strip test based on gold nanoparticles for the determination of aflatoxin b and fumonisins fecal shedding of a highly cell-cultureadapted porcine epidemic diarrhea virus after oral inoculation in pigs complete genome sequence of chyj , a highly virulent strain of porcine epidemic diarrhea virus in south china a new lateral-flow immunochromatographic strip combined with quantum dot nanobeads and gold nanoflowers for rapid detection of tetrodotoxin a turn-on competitive immunochromatographic strips integrated with quantum dots and gold nano-stars for cadmium ion detection identification and quantification of eight listeria monocytogene serotypes from listeria spp. using a gold nanoparticle-based lateral flow assay this work was conducted in the guangdong province key laboratory of molecular immunology and antibody engineering and guangdong haid institute of animal husbandry & veterinary. this manuscript has been thoroughly edited by a native english speaker from an editing company. editing certificate will be provided upon request. this work was supported by the national key research and development program of china ( yfd ). the funders had no role in study design, or the collection, analysis, and interpretation of data. in addition, they were not involved in the writing of the report or the decision to submit the article for publication. the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. molecular immunology and antibody engineering, jinan university, guangzhou , people's republic of china. in conclusion, a new ica based on mabs prepared by csfia was developed in this study. the gold nanoparticle signal of the test strip was of superior strength with very low background noise. the lod of the new ica was . μg/ml ( . × tcid /ml) and the liner detection range was . to μg/ml ( . × to tcid /ml). in addition, the new ica exhibited high specificity with little interference from swine stool, and could achieve recoveries ranging from to . % in spiked samples. compared to rt-pcr and elisa, the new ica does not require sophisticated instruments and training. relative to commercial test strips, the new ica provides more accurate detection of pedv in swine stool samples from south of china. our study highlighted the potential of the on-site application of this new ica for diagnosis and prevention of ped. additional file : figure s . authors' contributions hb, fx and yj performed the laboratory tests and drafted the manuscript. yt and aj conceived the study and participated in its design. lw and sd participated in the data analysis and results interpretation. all authors critically read and contributed to the manuscript, approving its final version.ethics approval and consent to participate all samples were obtained from healthy or naturally infected animals in the field by qualifiers. therefore, no aggressive operation was conducted against pigs for sampling purpose and no pigs were sacrificed in this study. the study used mice for generation of mabs and those mice had to be sacrificed. the mice were euthanized by cervical dislocation. thumb and forefinger were used to press down on the mice's head. the other hand grabbed the mice's tail and pulled it slightly back to the top to make the cervical spine disengage. the spinal cord was separated from the brain and the animal died immediately. there was no destruction of brain or section of major blood vessels in the neck during the process. all animal experiments were performed using protocols approved by laboratory animal ethics committee of jinan university. not applicable. the authors declare that they have no competing interests. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -vpg sfsk authors: pather, nalini; blyth, phil; chapman, jamie a.; dayal, manisha r.; flack, natasha a.m.s.; fogg, quentin a.; green, rodney a.; hulme, anneliese k.; johnson, ian p.; meyer, amanda j.; morley, john w.; shortland, peter j.; Štrkalj, goran; Štrkalj, mirjana; valter, krisztina; webb, alexandra l.; woodley, stephanie j.; lazarus, michelle d. title: forced disruption of anatomy education in australia and new zealand: an acute response to the covid‐ pandemic date: - - journal: anat sci educ doi: . /ase. sha: doc_id: cord_uid: vpg sfsk australian and new zealand universities commenced a new academic year in february/march largely with “business as usual.” the subsequent covid‐ pandemic imposed unexpected disruptions to anatomical educational practice. rapid change occurred due to government‐imposed physical distancing regulations from march that increasingly restricted anatomy laboratory teaching practices. anatomy educators in both these countries were mobilized to adjust their teaching approaches. this study on anatomy education disruption at pandemic onset within australia and new zealand adopts a social constructivist lens. the research question was “what are the perceived disruptions and changes made to anatomy education in australia and new zealand during the initial period of the covid‐ pandemic, as reflected on by anatomy educators?.” thematic analysis to elucidate “the what and why” of anatomy education was applied to these reflections. about anatomy academics from ten institutions participated in this exercise. the analysis revealed loss of integrated “hands‐on” experiences, and impacts on workload, traditional roles, students, pedagogy, and anatomists' personal educational philosophies. the key opportunities recognized for anatomy education included: enabling synchronous teaching across remote sites, expanding offerings into the remote learning space, and embracing new pedagogies. in managing anatomy education's transition in response to the pandemic, six critical elements were identified: community care, clear communications, clarified expectations, constructive alignment, community of practice, ability to compromise, and adapt and continuity planning. there is no doubt that anatomy education has stepped into a yet unknown future in the island countries of australia and new zealand. australian and new zealand universities commenced a new academic year in february/ march largely with "business as usual." the subsequent covid- pandemic imposed unexpected disruptions to anatomical educational practice. rapid change occurred due to government-imposed physical distancing regulations from march that increasingly restricted anatomy laboratory teaching practices. anatomy educators in both these countries were mobilized to adjust their teaching approaches. this study on anatomy education disruption at pandemic onset within australia and new zealand adopts a social constructivist lens. the research question was "what are the perceived disruptions and changes made to anatomy education in australia and new zealand during the initial period of the covid- pandemic, as reflected on by anatomy educators?." thematic analysis to elucidate "the what and why" of anatomy education was applied to these reflections. about anatomy academics from ten institutions participated in this exercise. the analysis revealed loss of integrated "hands-on" experiences, and impacts on workload, traditional roles, students, pedagogy, and anatomists' personal educational philosophies. the key opportunities recognized for anatomy education included: enabling synchronous teaching across remote universities across australia and new zealand commenced the new academic year in february and march . for most institutions, it was largely business as usual. few realized the extent of disruption and the pace of change that the unfolding covid- global pandemic, caused by the severe acute respiratory syndrome coronavirus (sars-cov- ), would impose upon all higher education (evans et al., ) . the first covid- cases were reported in australia and new zealand at the end of january and february (who, ), respectively, and were related to people travelling for tourism, work or study. even though most universities at first adopted a "watch and wait" approach, it became quickly evident that a higher education sector interruption was imminent (truu, ) . the extent of this disruption was evidenced by an almost immediate restriction on business travel for many university staff, initially to china (perpitch, ) ; and a resulting large number of australian and new zealand anatomy academics cancelled plans to attend international meetings and conferences. as the governments acted to prevent the pandemic spread, some university leaders drew on the experiences and expertise of their faculty, and acted quickly to source equipment, manage logistics, and provide in-time assistance to support the university's continued operations. in the background, core university business appeared to continue as usual. managements' "watch and wait" approach was perceived to be passive, causing some staff and student distress with the apparent lack of decisive action. university leaders, however, were carefully monitoring the situation to delay an inevitable transition to remote learning for as long as possible. at the beginning of march, the signs of higher educations' imminent disruption presented as australia and new zealand entered the "protect" phase of pandemic management learnt from past corona virus experiences (collignon, ; de wit et al., ) . by mid-march, the responsibility fell on academic staff to actively repurpose and redeploy resources, upskill their digital competencies, and develop new material to transition traditionally face-to-face (f f) and blended programs to a remote learning and/or online education delivery mode (johnston, ) . like in many countries, australia and new zealand included, technology-integrated learning has been embedded in medicine and allied health programs for some time (harden, ) . anatomists in this region have been actively involved in the development of digital resources and in curriculum reform (green and whitburn, ; colibaba et al., ; otton et al., ; green et al., ; birbara et al., ; ho et al., ; birbara et al., ; o'rourke et al., ) . anatomy education, however, has never before been delivered solely online or remotely for medicine and allied health programs in these countries. the tertiary education quality and standards agency (teqsa), which is the mandatory independent national quality assurance and regulatory body for higher education in australia (supporting information table ), acted quickly and decisively, enabling rapid educational transformation by announcing to the sector a broad reduction of the regulatory burden for universities managing covid- pandemic challenges (saunders, ) . this deregulation provided universities with approval to effect changes to delivery modes, as well as to provide remote learning to students who were offshore. this last aspect is critical to higher education in australia which serves a large international student body (davies and karp, ) . in , , students enrolled with australian higher education providers were on student visas and comprised a third of the student population (ferguson and sherrell, ) . during march , an overwhelming number of international students were forced to return to their homeland as the pandemic spread. the teqsa caveat, however, was that: "providers should assure themselves that such arrangements [changes to program delivery] maintain assessment and quality standards and are appropriately documented" (saunders, ) . most institutions were, thus able to rapidly initiate a business continuity plan enabling students to continue the academic year, if they chose. in quick succession over the last weeks of march , medicine and science faculties of most universities in australia and new zealand converted to online and/or remote delivery as university staff moved into a new paradigm of "working from home" (wfh) arrangements. defined by simonson et al. ( ) , remote/distance learning refers to institution-based, formal learning, where the learner and instructor are physically separated, and where interactive telecommunications systems are used to connect learners, resources, and instructors. in part, the business continuity plan (especially for medicine faculties) in australia was driven by pragmatism to ensure a functioning health care system in , which relies heavily on graduating medical students entering the system as junior doctors (interns) each year. for the discipline of anatomy, this decision has potentially fundamental consequences. the governments mandated covid- response resulted in restricted movement and physical distancing requirements. the regulations initially constrained anatomy laboratory access, but quickly progressed to a prohibition of students' laboratory access entirely as wfh and remote learning arrangements became the new normal. the initial stage of this transition may be particularly challenging to those in the anatomy discipline as many conventional anatomy education pedagogies rely on "hands-on" practical experience; it is through these small groups that many anatomy educators identify and respond to students' learning needs especially those at-risk of underperforming (kumar ghosh and kumar, ) . furthermore, delivering anatomy education solely online or at a distance, if only for a short period, challenges the long-held educational philosophy of many anatomy educators (pather, ) . additionally, for those who strive to frame their anatomy programs through a lens of ethics and humanism (Štrkalj and pather, ; evans et al., ; hildebrandt, ) , there is a need to work harder to connect students to these paradigms when educating solely within the digital realm, and in the absence of a once-living person (stephens et al., ; kumar ghosh and kumar, ) . notwithstanding these issues, the remarkable mobilization, commitment, speed, and agility of the australian and new zealand anatomy community, including academic and support/technical staff, presents the beginning of a historic bridge into an unknown future. the continuity of anatomy education during the covid- pandemic in australia and new zealand is not "business as usual" and is not likely to return to the pre-pandemic approaches again, given the extent of the present changes. this study, therefore, aimed at documenting the shared experiences of anatomy educators in changing their teaching practice during the early period of the covid- pandemic within australian and new zealand higher education. participants were voluntarily recruited via an email invitation to anatomists serving in leadership roles in the australia and new zealand association of clinical anatomists (anzaca), with snowballing recruitment following. the resultant participant group, and co-authors, included academic anatomists representing ten institutions across these two island countries. in australia, this group represented four of the australian states and territories, and five of the "group of eight" universities (leading eight australian research-intensive universities) (table ) . in new zealand, the participants represented one of the (only) two new zealand universities that teach anatomy. all participants taught anatomy (including neuroanatomy), histology and/or embryology to a variety of student cohorts including science, biomedical science, allied health, and undergraduate and graduate medicine, as well as junior (i.e., resident) and postgraduate (attendings) doctors using multiple approaches before the pandemic (supporting information table ). the research question was "what are the perceived disruptions and changes made to anatomy education in australia and new zealand during the initial period of the covid- pandemic, as reflected on by anatomy educators?." all participants were asked to reflect on the experience of delivering anatomy education from the start of the academic year through to the end of march . this descriptive qualitative account of anatomy education disruption focusses on the early stages of the pandemic within australia and new zealand, with the methodology of adopting a social constructivist lens, wherein the truth is negotiated by those experiencing it (rees et al., ) . thematic analysis to elucidate "the what and why" of anatomy education was applied to these reflections, as outlined by nowell et al. ( ) . the names of institutions were de-identified during thematic analysis. six phases of coding were undertaken with phase ("data familiarization"), phase ("initial coding"), and phase ("theme searching"), carried out by m.d.l. phases and ("theme review" and "naming themes") were carried out separately by two authors (m.d.l., and n.p.). phase ("findings report production") was initially drafted by m.d.l., with n.p. providing feedback, debating, and discussing interpretation discrepancies. while these stages appear linear, each progressive stage was iterative, and thus previous stages were addressed where needed during phase . all analyses were performed in microsoft word (microsoft corp., redmond, wa) as higher order complex coding was not undertaken due to the research question. this approach to thematic analysis included a team-based reflexive exercise (barry et al., ) by those undertaking the analysis (m.d.l., and n.p.). both authors have extensive experience in qualitative research and value grounded theory in answering the research question, but they differ slightly in world views. while one allows the research question to dictate the methods, the other struggles with the idea of quantitative analysis ever being objective, due to inherent complexities of the natural world. both thought the opportunity to reflect, and learn from others' reflections, was a valuable opportunity. the fears expressed in undertaking this study included concern for peer wellness and rapidity of data analysis-but overall, both authors thought the study merits outweighed the risks. this study was approved by the monash human ethics review board research ethics committee (muhrec # ). in australia and new zealand, f f laboratory practical sessions are central to anatomy teaching (table ) . participating anatomy educators' reflections outlined the progressively increasing restrictions placed on f f teaching (e.g., increased physical distancing, cancellation of practical sessions, or complete campus lockdown). these restrictions were coupled with an almost consistent university message: the universities in australia and new zealand are "open for business" with a status of "business as usual." this disconnect between university messaging and imposed social constraints appeared to contribute to at least some of the shared academic anatomists' challenges outlined below. one new zealand academic summed up the higher education pandemic setting concisely in stating: "there is no doubt from our perspective that the world is suddenly a different place." in continuing anatomy education during the initial pandemic period, nearly all universities appeared to employ a mix of synchronous and asynchronous (chen et al., ; watts, ) online activities (table ) , with some institutions having used evidence-based online activities to deliver the curriculum prior to the pandemic. notably, nearly all chose at least some synchronism to mitigate the loss of the practical "hands-on" synchronous live streamed small group sessions a member of the "group of eight" leading australian research-intensive universities. almost all donor programs were suspended in the face of the pandemic. lectures typically relied on prerecorded material, a mix of asynchronous and synchronous teaching was used for practical modification. active learning engaged large group webinars or discussion boards to facilitate class discussion; f f, face-to-face. component of their delivery. of the institutions included, six supported a teaching "pause" (table ) . this provided students a short time to relocate to home, if appropriate. it also, even if notionally, acknowledged the significant work required from academic staff to change the mode of delivery within a limited timeframe, and gave credence to the ubiquitous messaging that the health and well-being of the university community is of primary importance, especially during the covid- pandemic. the urgency of the situation was evident in all narratives. each anatomists' reflection tended to focus on identifying a . many australian and new zealand anatomy educators used digital resources to overcome the legal and ethical limitations related to human donor programs which often prohibit the sharing, photographing or recording of donor material. some institutions were offered a brief ( week) pause to convert a semester of teaching into online approaches, while many others were not. despite typically engaging demonstrators only for f f teaching, many institutions engaged sessional demonstrators in this transition -though their roles changed. while some still led online delivery of material, many were engaged to help develop resources for this pandemic anatomy teaching. dvr, three-dimensional virtual reality. temporary solution, with many also incorporating and planning for future practical laboratory-based intensives ( table ) . the need for a balanced teaching approach, staff adaptability, and well-being support were discussed in nearly all reflections. as expected, some academics found the experience of accelerated change exciting and fruitful, while others found this experience daunting and worrisome. universally, there were shared concerns about the extraordinary workloads this transition required. some academics reported that even when commercially available material was used in teaching, the time spent curating and annotating this to ensure learning outcomes were met, was exorbitant. a reflection from one australian colleague highlights the increased workload: "online teaching extends the working day and the working week (to now include weekend work); the volume of email has increased exponentially." almost all academic anatomists reported that anatomy education is likely to change permanently given the scale of change during the pandemic, with some concerned that this change will call into question traditional laboratory-based approaches, in favor of modern (now trialed) online and remote learning approaches (table ) . this concern was compounded as many academics reflected that these curricular changes, despite attention to quality, were a rapid response to an unprecedented situation, allowing little time for reflection and evidence-based refinement. there were a variety of personnel-and infrastructural-related challenges shared across the australian and new zealand academics' reflections. these challenges fell into four categories: staff (faculty/academic staff and technical/professional staff), students, infrastructure and resources, and curriculum changes to accommodate online and/or remote delivery of anatomy education. with respect to personnel, there were multiple staff categories that were perceived to be affected by the pandemic teaching context; for all staff (regardless of previous role), there was a drastic change in the type of work that they were expected to do. the academic staff appeared to have the least professional role change, as many reported that they were, themselves, still focused on pedagogy; the expectations and skills for executing this new pedagogy, however, was different. a common challenge reflected on was that of information technology (it) skills, and the lack of prior training or knowledge for effective online education delivery practices. technical staff and anatomy sessional staff/demonstrators (defined in supplementary table ) were perceived as having some of the largest role transitions. some anatomy educators noted that demonstrator roles changed from leading f f small group discussions to that of digital media development and/ or to small group instruction via streaming platforms such as zoom ® (zoom video communications, inc., san jose, ca and microsoft teams ® (microsoft corp., redmond, wa) ( table ). in contrast, other anatomists commented on the sudden elimination of the demonstrator role due to the pandemic's impact on university finances. colleagues from one australian university described their experience: "one of our first thoughts went to our casual demonstra-tors…this sudden change would remove their opportunity to extend their teaching experience, develop their knowledge and skills and reduce their income. to rectify this, we immediately instigated mechanisms to involve our demonstrators in the process of developing our remote learning opportunities … for one anatomy practical that required transformation into an online format in less than hours, they [the demonstrators] came into the laboratory after hours to create demonstration videos." technical staff appeared to similarly be learning new skills and pivoting their roles, as illustrated by another australian anatomists' reflection: "our tech [nical] team have been enlisted to create videos of rotating models so that students have at least a visual impression of these resources that are typically available to them in a resource area on each campus." professional and technical staff faced the additional stresses related to job security. initially this stress was related to the seemingly seamless way in which academic staff mobilized to deliver a program of online anatomy education, and was exacerbated when some departments took the strategic decision to temporarily suspend the body donor program due to uncertainty regarding the risk to covid- exposure (table ) . as the pandemic further unfolded, and with increased communications of university budget deficits, the future for professional staff remains tenuous. interestingly, almost universally the academic anatomists' reflections included perceptions that both demonstrators and technical staff appeared to value these new roles and demonstrated skills of adaptability and resilience. the reflective narratives about the academics' own role (and role of their academic team) often also illustrated gratefulness for the flexibility of their peers. a major challenge for all participating academic anatomists was the time investment to support the pandemic's curricular change. there were also many who reflected that the increased workload was not accompanied by the usual rewards of student interaction, a shared sentiment of the anatomy educators expressed in one anatomist's reflection: "we go into these roles because we truly love watching students learn, not being able to see that in a traditional sense does make this workload harder" and this was further explained by an anatomist from another institution: "for some academics the anticipation of contact with students [in the usual f f delivery] is something to look forward to, but this is difficult [during the pandemic] due to the city-wide physical distancing laws." as mentioned, some universities did "pause" teaching to accommodate the transition to online delivery (table ) . this "pause" was for a relatively brief period (< or up to weeks) considering the length of a semester (~ - weeks typically) and the number of learning activities that needed modification for online/remote learning. the challenge was compounded as universities moved to wfh, and with primary and secondary schools increasingly transitioning to home-based learning. this was an unprecedented experience and has meant that academics already working to difficult timelines with a challenging workload were also adjusting to wfh, and for some, with the additional tasks associated with concurrent childcare and home-schooling. the academic reflections included a focus on perceived student-centered challenges. academics expressed awareness of students concerns that centered around future degree and career progression, across the participating universities. according to the academics, students appeared to face financial pressures due to lost income, resulting in concerns about university fees, and for many, a forced intermittence. some of the perceived student challenges included managing student perceptions of "missing out" or "getting what they [the students] paid for." there was an observation that these student concerns were at least, in part, due to the universities' messaging on expectations versus what was achievable by staff in the timeframe available, and within the pandemic education context. also impacting these perceptions may be the pre-pandemic emphasis of anatomy education on, and the now lack of exposure to, human donor material, which is often perceived as a signature experience of the discipline. a colleague summarizes some of the student concerns: "students were concerned about not having access to learning from human donors, which they perceived as the best opportunity to integrate concepts with the 'real' experience. the anatomy lab was where deep understanding of anatomy was achieved. students further reported that they struggled without the f f interaction with academics and tutors in the lectures and labs. in general, the student body was struggling with a lack of motivation without direct teacher interactions.... however, they [students] also highlighted the significant shift that they are making in a short time to adjust from f f to online learning, and without the benefit of physical interactions with peers." academics themselves also had concerns about student learning, specifically around equity and access. this concern was compounded when considering the implementation of synchronous learning activities, and students' repatriating. this enforced geographical distancing meant that students were located across multiple time zones, with some returning to countries with restricted or poor internet access. australia and new zealand also have internet network accessibility and reliability limitations, particularly in rural and remote areas. together, these potential learner challenges were considered in the redevelopment of australian and new zealand anatomy education, and (at least in part) accounts for the suite of synchronous and asynchronous activities (table ). regarding resources and infrastructure, the challenges expressed by anatomy educators are likely globally universal in university programs, including access to software and support for online teaching, technical failures, and network sustainability. however, unique to anatomy education are some of the ethical and medical considerations related to working with human donor resources. multiple state/regional legislations pertain to body donor programs and consent for donation. specifically, the ethical and legal constraints of sharing and displaying digital images of prosected human donor bodies/body parts, increased the challenges to anatomy online education in australia and new zealand; the net result was a reliance on proprietary digital anatomy resources (table ). in addition to the impacts on teaching, reflections communicated concerns about body donor programs sustainability and continued maintenance in the face of the present acute global health crisis. anatomy lectures appeared to be the least complicated of all activities to translate in the pandemic, while anatomy practical experiences and assessments were consistently the most challenging to redesign across these two countries (table ) . lectures. while some anatomy educators chose to livestream lectures on campus and/or from home, most chose prerecorded asynchronous approaches by re-using lecture recordings from previous years or developing new recordings. this decision reportedly allowed academics to focus effort on more complicated curricular translations (i.e., practical sessions and active learning), as noted by one reflection: "in the covid- context, most course conveners released the pre-recorded lectures from the year before. this provided the opportunity for academics to have cognitive capacity to concentrate on upskilling their comfort with other technologies, and to reorganize material for the online space." these prerecorded lectures were reportedly often supplemented with additional lecture material, which included short concept videos and formative assessments ( table ). the sentiments expressed in many reflections was summed up by one colleague: "one strategic decision was to move away from big topics, by encouraging the breakdown of long lecture content into digestible chunks. the organization, search and review for existing digital material on [the] world wide web were additional tasks that were both time consuming and time 'robbing'." some academics incorporated interactive lectures, mirroring some of the active learning principles. active learning, by definition, depends on student interaction to foster learning, and the opportunities for learner reflection (haidet et al., ) . much effort was placed into translating these same principles online using interactive applications like kahoot! © (kahoot! a.s., oslo, norway) and slido © (slido s.r.o., bratislava, slovakia), and incorporating formative quizzes, live streaming, and applied anatomy tasks such as clinical case activities. one academic describes the active learning translation for a medical anatomy curriculum: "our active learning sessions… allow for students' application of learned knowledge in the context of clinical uncertainty. to develop our online learning activities, we first asked ourselves what were core aspects we wanted to reproduce online? for us this included: clinical reasoning, taking chances, and learning from peers. from this, it was decided to develop a series of discussion forums… we gave clear instructions on what was an appropriate approach to responding.... students progression through [clinical] cases required them to work through the previous case, as would happen during the faceto-face active learning session… peers and facilitators were the primary source of feedback and re-direction if a student went off track, again emulating the teamwork needed for successful active learning. once a learner had gone through each case, they were then able to access post-class videos which touched upon key anatomy knowledge." practical experiences. many institutions reflected that student-teacher interaction was a desired attribute of practical sessions and replicating this online required supporting synchronous delivery experiences (table ) . many anatomists reflected a plan for intensive practical experiences postpandemic to make up for the lack of exposure to authentic human donor resources during the remote learning phase ( table ) . some of the shared university practical experiences is represented in one colleague's peer reflection: "for our practical experiences, we decided to focus on two key attributes, the short-term knowledge gains, and opportunities for students to be exposed to experts. we engaged the zoom platform, because of its capacity to allow for user interaction. the medical imaging stayed much the same; herein demonstrators shared curated imaging, allowing students to use zoom's "annotation" function to answer imaging identification questions…tutorials were almost exactly the same with students engaging in presentations related to assigned learning objectives. the dissection component was the area that entirely changed." many institutions integrated practical videos, both prerecorded (pre-pandemic) and novel recordings were developed for supplementing the new synchronous online activities ( table ). the purpose of the videos varied and were highlighted in a colleague's reflection: "explanatory video to describe how and why we were making these changes, and how to use the four (three commercial and one in-house) online anatomy resources… [and] staff prepared additional short videos to emphasize key concepts for each weekly prac[tical] class using these online resources." many used widely available videos from youtube (youtube llc., san bruno, ca) or proprietary anatomy software to minimize "reinventing the wheel," but even this approach resulted in significant workload to both "source appropriate videos" and annotate them, with suggestions ranging from ~ hours for a -hour active learning session to ~ hours for a single practical conversion. for those who had already begun transitioning to technology-enhanced learning before the pandemic, the rapid online transition was perceived as a step backwards in their planned implementation as it was done with limited time for reflection and testing. many also highlighted concerns that this rapid online shift may result in their institutions questioning the role of human donor material altogether. assessments. at the time of writing this report, assessments remained the most complicated and yet to be determined component of australian and new zealand anatomy education. reflections from each university indicated that assessments were to be online. while online practical assessments have previously been effectively trialed (inuwa et al., ) , both the assessment approach and the platform for administration still needed to be determined within a short timeframe. the challenges were summarized in this statement: "we want to ensure that our assessment is a true reflection of learning, remains robust, maintains integrity and is secure." some reflections also outlined a plan to prepare the student body for the anticipated changes to the assessment style: "any assessments that we deliver will be preceded by at least one formative examination in order to familiarize ourselves and the students with the online assessment process." many academics shared awareness of student collusion risks and a difficulty with assessment invigilation; some translated this to developing assessments where collusion became irrelevant using variations of formative assessments or relative grading approaches. other universities reported simply accepting collusion as inevitable in their solutions, as exemplified by one strategy in which assessment incorporated higher order questions: "the questions involve interpretation and analysis rather than recall of information and so whilst we cannot control students cheating, the nature of the questions reduces the likelihood of them locating the answer. if students collaborate then at least they have engaged together in reaching a solution." others modified their assessment approaches to minimize the chances of collusion using, for example, "flag race tests [aka practical exams] … conducted [online with] randomized flags." they report that: "this now effectively becomes an open-book test, so to minimize collusion and maintain some academic rigor, the test will be run at a single time for all students and flags are randomized so that they [students] are not all getting the same question (even if they are sitting side by side.)". one institution had further, in partnership with students in decision-making during the pandemic, implemented pass-fail grading reporting: "students were concerned that others in the student body would resort to extreme measures of colluding or compromise their academic integrity, which would be unfair on those who did not." still others were adjusting assessment weighting to minimize the drive for collusion, and were considering sensitivities around what is being examined: "we are creating our own assessments deploying them [online] as timed low-stakes summative tests. care must be taken to make sure non-sensitive images are used as students may screenshot and distribute questions." even with these mitigating measures, assessment remains challenging-how do we build assessment with constructive alignment for pandemic anatomy education? constructive alignment is based on constructivist theory wherein the learner constructs knowledge through learning activities which are pre-aligned with outcomes and assessment (biggs, ) . adjusting assessments for students with learning disabilities and those requiring extra time for completing assessments further extends the complexity of ensuring a robust assessment practice delivered remotely, within a limited timeframe. this is further compounded when assessing a student body with heightened anxiety due to the constant media reporting and ever-changing circumstances presented by the pandemic. there were also some recognized opportunities that the pandemic presented including as previously noted, the rapid skill acquisition in online pedagogy (schmidt et al., ) and skills in digital media production. with this in mind, and considering the changes already initiated in a short timeframe, the pandemic provided some with an impetus for curriculum review and strategic development of educational resources that would be useful after the pandemic, especially if these further enhance access and equity: "we are developing resources that can be utilized even when we are back to functioning normally. if the resources are aligned with the curriculum content and approach, then they can definitely supplement the practical classes ..." many reflections universally shared benefits such as gratefulness for both peers (staff) and students, and reported enhanced teamwork and skill acquisition of all involved (both staff and students). of note, most participants reported a positive student response, even if this was initially negative. as the pandemic progressed, students increasingly responded to the anatomy learning experience with unsolicited positive feedback, and in some cases also with concern for staff. the timing of the pandemic is of note for the island countries of australia and new zealand. the pandemic's "arrival" coincided with the beginning of the academic year, a very different time to that of their northern hemisphere counterparts (who were nearing the end of the academic year). the implication of this, is that changes to the anatomy education delivery, even if only limited to the first half of , potentially will have knock-on impacts across the entire academic year with respect to both curriculum delivery and assessment. as the covid- pandemic unfolds, and in the face of the significant disruption, the combined experiences and reflections of anatomy academics identify two main contributions to the practice of anatomical education in australia and new zealand. first, there are both opportunities and challenges presented with the rapid change in anatomy education, and there are related significant impacts on workload and professional roles. these were exemplified in the rapid upskilling of human resources, flexibility in redefining roles, and creativeness to enable and support continued learning at a distance. second, there are the perceptions of the impact on pedagogy, technology, higher education institutions, staff, students, and, of course, on personal educational philosophies in both the short and long term. in this domain, concerns on the loss of an integrated "hands-on" laboratory experience, and the lack of being physically present, were raised. the insights into these two areas will have important implications for anyone contemplating anatomy education in the future. while it is an unchartered time in the history of higher education, as always, there are lessons that can be gleaned from disruption, and anatomy education in australia and new zealand to accommodate the acute covid- crisis presents several insights (fig. ) . of primary importance is the care of the whole community. care should be taken to ensure that there is a safe environment. change often creates anxiety for some, and rapid change in response to the covid- pandemic is disruptive for both students and staff. for staff that deal with body donations, the pandemic raised concerns about both job security and risk of exposure if a body donor was a virus carrier. it is imperative that department leaders are aware of these concerns and find means to be "present" to engage in conversations and develop plans to mitigate risk to all constituents of the anatomy community. these concerns whether real or perceived, impact well-being. it is, therefore, imperative for department leaders to act quickly in circumstances where exposure to potential harm (e.g., sars-cov- virus) is unknown and to mitigate any threat to the health of the community, even if it requires temporary suspension of body donor programs. equally, student mental wellness is of concern to the academic anatomist, both prior to, and during the pandemic. while academics grapple with how to deliver anatomy education online, there needs to be an awareness that students who had previously experienced anatomy as a hands-on subject, or had preferred f f learning, require support in the transition to learning remotely (blackley and sheffield, ) . in this remote learning environment, the lack of physically present peers and instructors can lead some to have negative learning experiences. this raises concerns about the cognitive load placed on students through the change of learning environments, and whether the pace of change during the pandemic leaves too little mental capacity to construct knowledge (schwonke, ) . ideally student learning in this new environment requires explicit monitoring of cognitive processes to minimize cognitive overload, as advocated by valcke ( ) . broadbent and poon ( ) highlighted, through systematic review, four strategies students require for online learning: time management, metacognition, effort regulation, and critical thinking. in the short time to transition to remote learning during the pandemic, providing structure was a key element of effective support for managing stress and anxiety, and anatomy educators used a variety of strategies to provide structure like scaffolding learning through structured weekly activities, packaging topics into digestible chunks to reduce cognitive load, the use of short concept videos and quizzes to regulate effort, and interactive synchronous learning to develop critical thinking and social interactions. from the authors experience, students have also been reassured by knowing that hands-on laboratory sessions would be provided post-pandemic to provide opportunities to review cadaveric prosected specimens and surface and living anatomy, and possibly undertake dissection. one of the challenges of the current landscape is that messaging understandably appears changing, unclear and often conflicting. clearly communicating, even when the answer is still being discussed, is essential and will ensure reciprocity and cooperation among students (chickering and gamson, ) . as academics, who were also managing change for students, modelling effective communication strategies and approaches is useful to alleviate any change-induced stress. communication of expectations, as well as simple guidance on managing the online space is of great importance and can make a positive impact on learning (broadbent and poon, ) . some examples of this include clarifying the expectations around the expected daily/weekly progress and assessment criteria, and providing formative assessment opportunities as a preamble to high-stakes assessment tasks, as highlighted by the academics' reflections. in the light of increased student anxiety during the pandemic, communications should be carefully framed within positive messages of support and in a context of open dialogue. useful strategies employed during the pandemic included using anonymous dialogue platforms like slido © to allow students to ask questions in the comfort of anonymity, discussion boards to enable asynchronous student-teacher interactions (green and hughes, ) , and including students in the decision-making process affecting aspects of anatomy delivery, for example, assessments. of note, during this pandemic education delivery, both the academic staff and students described a loss of in person interaction and its impact on their individual motivation. while this has previously been connected to student disengagement in the online learning environment (gillett-swan, ) , the impact of this loss on staff has only recently been reported in the context of embedded-reward systems in higher education (cuseo, ) . as workloads and roles morph, effective change management strategies can be helpful, including clarifying stakeholder expectations. this is especially important given the increasing concern over the last two decades about mental wellness among infographic of shared australian and new zealand anatomy education teaching approaches during the covid- pandemic. scoping implications for this teaching crossed multiple teaching modalities summarized as the six cs, and affected all stakeholders (students and staff) including: change and flexibility, clarify expectations, clear communication, constructive alignment of new material, a focus on community care, and continuity planning in the face of this global health emergency. lectures and active learning tended to engage asynchronous online approaches, using prerecorded videos and discussion boards, while practical activities tended to be synchronous streaming approaches combined with a reliance on future intensive experiences. assessment was the most widely varied aspect across these two countries. all approaches tended to accept collusion as a risk to online assessments, and educators attempted to mitigate this risk by delivering questions with randomized sequencing for each student, decreasing weighting of assessments, making assessments pass or fail, or embracing teamwork as part of the assessment strategy. university academics even in the absence of a crisis (watts and robertson, ; gulliver et al., ; kinman, ) . existing evidence suggests that academics are already overcommitted to their work due to implicit system rewards (hamilton, ) . in the absence of a pandemic, the increase in educators' workloads in developing online resources (green and whitburn, ) and in transitioning to remote and online delivery (kimball, ) is well recognized. managing and supporting students has been identified as the most demanding aspect of digital learning (canninzzo et al., ) . this correlates with the reflections of a large number of participants regarding the increased workload, the extended online work day/week, and the increased student correspondence. regarding the latter, kimball ( ) explains that in remote learning, learners have a perception of a "rolling presence" which can make educators feel pressured to spend large amounts of time interacting with students who perceive online education as "always open" for business. the social and personal impact of the rapid response by anatomy academics to transform to a highly demanding form of delivery (i.e., distance/online) is yet to be determined. it is reasonable to expect that discussions and plans to reset stakeholder expectations will be required, especially if this pandemic continues for an extended period. as workloads explode, there is a need for leaders to provide immediate assurance, acknowledgement of the situation and empathy for the challenges faced with rapid change. those in leadership roles, have the added responsibility to advocate for staff, especially considering high expectations and the complexities of wfh arrangements. clarifying expectations of academics is imperative. for academic colleagues, it is impossible to quantify the time required for repurposing and sourcing resources, but acknowledging this reality is useful, as is acknowledging all who contribute to delivering the learning experience. in good education practice, constructive alignment is paramount. in a pandemic, alignment, if clearly articulated, will potentially aid students in making meaning of the change and will be reassuring and decrease anxiety. in delivering anatomy education remotely and online within a changing pandemic landscape, constructive alignment remains a challenge; a simple effective process to ensure alignment with learning outcomes, activities, and assessment is, however, required. as saunders ( ) posits, distance teaching requires teaching practices to change, and "to change the way in which you teach is a significant undertaking." there are several fundamental elements of effective online pedagogy design (chen et al., ; martin and bolliger, ) employed in delivering anatomy teaching during the pandemic, these elements were variably highlighted and included providing feedback through quizzes, establishing social connections, active facilitation and using a range of technologies. one approach highlighted selecting a pedagogical element to emphasize through the delivery (e.g., active learning) rather than focusing on issues such as infrastructure, policies and budget. even with this foresight, the aspect of remotely delivering assessment requires more deliberation, and institutional resources (kirkwood and price, ) . it is expected that this is an area that australian and new zealand universities will need further investment in. at some stage, once the crisis is over, activities undertaken now will have to be reviewed. for this reason, clear documentation of expectations and modifications made (what, why, and how) will be useful. there is, however, little opportunity with the present pace of change, for an adequate change documentation process. uncertainties also remain around how documentation will be reviewed by professional accreditation bodies, and for australia, teqsa. no doubt there will need to be a targeted program of evaluating competencies and providing in-time education to address any perceived learner knowledge gaps. it is hoped that this compensatory process will also heed the evidence on the benefits of cadaveric-based learning for medical students (estai and bunt, ; flack and nicholson, ) . it will, however, be important to determine what perceived gap, if any, is being addressed before a compensatory activity is planned (wilson et al., ) . at that stage, and with time, there will also be opportunity to evaluate whether other digital resources and immersive learning experiences can be used to address knowledge gaps (doubleday et al., ; losco et al., ; birbara et al., ) . as we cope with this pandemic, being able to compromise, and adapt in practice and curriculum design and teaching delivery is important. anatomy academics' reflections on persevering and adapting to deliver anatomy education amidst constant and daunting change is possibly an indication of a commitment of anatomy educators to the education sector, student body, and discipline. given the limited time available for transition to remote/online delivery, the authors experiences demonstrated an almost consistent strategy of repurposing existing material. this enabled academics to concentrate on redesigning activities related to higher learning outcomes usually attained through the practical components of learning in the anatomy laboratory. some anatomy educators planned later opportunities after the pandemic to address perceived gaps in knowledge. evidence suggests that the quality of remote learning materials needs to be higher than campus-based materials (kimball, ) and this has been corroborated more recently in the practice of developing online content for a blended anatomy course (green and whitburn, ) . however, an important aspect of pandemic change for anatomy academics themselves is to adapt self-imposed standards. it will take confidence to heed calls to compromise self-imposed excellence standards. as saunders ( ) explains, academics incur additional stress in online teaching with the increased pressure that prerecorded videos, case studies, and discussion boards are a permanent record of their knowledge and expertise. given the context of the pandemic, and the speed of change, it befits entire academic community to model self-care and moderation to those around, and to accept that current makeshift resources may not be a true reflection of the educators' abilities, but it will be fit-forpurpose in response to acute transitional change. one of the challenges of change in the paradigm of physical distancing regulations, is that it almost instantly cauterized the existing community of practice academics access in their home departments and institutions. anatomy academics, however, appear to be resourceful in effectively engaging with a wider community of practice to share not just experiences and capabilities but also resources. this was evidenced in the almost immediate role change of technical staff and demonstrators to develop digital resources, and through the sharing of resources and of experiences using social media communities (e.g., twitter inc., san francisco, ca) and by software developers and societies of anatomy (evans et al, ) . smaller communities like local departments of anatomy, have also utilized technologies such as whatsapp © (facebook inc., mountain view, ca), to troubleshoot through challenges, and motivate and aid staff well-being. as in past times of crisis, a positive outcome of the shared challenge is that it unifies communities around common goals. while this is certainly a time of justified anxiety, it is also a time when the positive and resilient aspects of connectedness and community come together to encourage and build each other up-even with physical distance. notwithstanding this, the rapid onset of the covid- pandemic, highlights the need for the discipline and for departments to be proactive in keeping updated with new pedagogies and to be embedded in wider communities of practice outside home institutions. as negative as it sounds, it is essential at this time (as at any) to develop and communicate a continuity plan. in a global health emergency, circumstances are likely to arise that a team member is unable to continue their responsibilities. inevitably, the pandemic highlights to those in leadership roles, the need for contingency planning and investment in staff upskilling. the disruption of anatomy education in response to the pandemic may, however, also be perceived as an opportunity to expand anatomy education more broadly beyond the traditional f f delivery model into the remote learning space. fully online models of anatomy education may have been impeded over the last decade by the lack of acceptance among anatomy educators. the quick response of the anatomy community in australia and new zealand demonstrates their flexibility and potentially enables the discipline to personalize education (gillett-swan, ) and to expand its reach to untapped learner pools, an increasingly important need as institutions enter a post-pandemic financial recovery phase. no doubt that whatever the context, the main inhibitor of remote anatomy education delivery will be the quality of the offering especially if deficient of a hands-on practical experience, time, support, and people capacity. some of the benefits of the pandemic-related disruption are already being recognized and include, for example, using live streaming to deliver lectures to cohorts of students distributed across multiple (sometimes even remote) campuses during clinical placements, thus addressing a challenge experienced by most australian and new zealand anatomy departments. this model could also assist students on extended periods of absence, like for example indigenous students attending community and family ceremonies and funerals. some anatomy academics have, indeed, perceived this rapid change as a novel opportunity to apply newly learnt pedagogies and delve into a freshly acquired space for modern education. there remain several limitations of this current profile of anatomy education during the early stages of the pandemic. while it uniquely captures a cross-section of experiences of delivering anatomy education in australia and new zealand, the reflections were not triangulated, and it does not include all anatomists or all anatomy departments in australia and new zealand. importantly, the participants narratives are a snapshot of their perceptions and views based on a one-off reflection during a period of crisis, and not a longitudinal account of their experiences. the constructivist approach to the study is an appropriate tool to examine anatomy education in the rapidly changing context of the pandemic, as it allows interpretation of experiences at different time points. a follow-up study with the participants post-pandemic would, therefore, provide deeper insights on how academic attitudes in this period of acute change have changed and matured, and how the experience has impacted their personal educational philosophies and their institutional practice of anatomy education. as the covid- pandemic continues to unfold in australia and new zealand, there is no doubt that university leaders and academics deserve recognition for their management and support to all the communities that they serve. their focused efforts in the face of global change, disruption, uncertainty, and potential volatility appears to ensure an effective and safe learning environment, and where possible, serve their nations and their institutions. for anatomy education, these decisions were particularly impactful in that they disrupted access to human donor body resources (a widely utilized discipline pedagogical tool) and forced change to ensure the continued delivery of anatomy teaching. several challenges were recognized by anatomy academics in this period including time, resources, and technical capability. professional and technical staff demonstrated role adaptability and assisted their academic colleagues in meeting teaching obligations. for anatomy academics, flexibility and adaptability enabled the continuity of anatomy education programs which were effectively fit-for-purpose in the pandemic context. interestingly, in person interactions between anatomy academic staff and students, an often-overlooked motivator, was uniquely highlighted as an integral part of the anatomy learning equation. of note, and in a time of crisis and uncertainty, anatomists appear to act and think like leaders-health and safety first, followed by academic standards, and developing flexible solutions for business continuity. there is no doubt that there has been a significant change in the teaching of anatomy in australia and new zealand over the last month. it remains, however, to be seen how the rapid change effected at this time correlates with student performance and satisfaction, and how the bridges that have been built impact on the future of anatomy education. the figure was designed in collaboration with kat orgallo, teaching resource support unit, faculty of medicine, nursing and health sciences at monash university. nalini pather, m.med.sci. (clin. anat.), ph.d., is a professor and the chair of anatomy at the university of new south wales faculty of medicine, sydney, nsw, australia. she teaches anatomy across multiple programs including medicine, allied health, medical science, and biomedical engineering students. her research group focuses on the applications of anatomy, visualization, and immersive technologies to clinical, and imaging specialties, and on medical education. using reflexivity to optimize teamwork in qualitative research constructive alignment in university teaching d modelling and printing technology to produce patient-specific d models virtual reality in anatomy: a pilot study evaluating different delivery modalities digital andragogy: a richer blend of initial teacher education in the st century self-regulated learning strategies and academic achievement in online higher education learning environments: a systematic review moral barriers between work/life balance policy and practice in academia a model for synchronous learning using the internet seven principles for good practice in undergraduate education exploring deep space -uncovering the anatomy of periventricular structures to reveal the lateral ventricles of the human brain swine flu: lessons we need to learn from our global experience student-faculty engagement a downward spiral: coronavirus spins australian universities into economic crisis. the guardian sars and mers: recent insights into emerging coronaviruses the virtual anatomy laboratory: usability testing to improve an online learning resource for anatomy education best teaching practices in anatomy education: a critical view going virtual to support anatomy education: a stop gap in the midst of the covid- pandemic human skills for human[istic] anatomy: an emphasis on nontraditional discipline-independent skills overseas students in australian higher education: a quick guide. parliamentary library research papers series what do medical students learn from dissection? 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metacognitive and self-regulatory demands in computer-based learning distance education research: a review of the literature how does donor dissection influence medical students' perceptions of ethics? a cross-sectional and longitudinal qualitative study commemorations and memorials: exploring the human face of anatomy australian universities defer exams, increase response to coronavirus outbreak cognitive load: updating the theory? synchronous and asynchronous communication in distance learning: a review of the literature who. . world health organization. coronavirus disease (covid ) situation report - breaking with tradition: a scoping meta-analysis analyzing the effects of student-centered learning and computer-aided instruction on student performance in anatomy phil blyth, b.h.b., m.b.ch.b., ph.d. (bioeng.) , is a senior lecturer in elearning in medicine in the department of anatomy, school of biomedical sciences, university of otago, dunedin, new zealand. he coordinates the elearning team within the mbchb program and teaches anatomy within the medical and science programs. his research interests include medical education and he has developed orthopedic surgical simulation apps. he practices within the emergency department. jamie a. chapman, ph.d., is a senior lecturer in human anatomy at the tasmanian school of medicine, college of health and medicine, university of tasmania, hobart, tasmania, australia. he coordinates and teaches histology in the first years of the mbbs course and coordinates a first-year, cross-campus human anatomy, and physiology unit. his research is focused on technology-enhanced learning and teaching.manisha r. dayal, ph.d., is a senior lecturer in human anatomy in the school of science at western sydney university, australia. she teaches gross anatomy, embryology, and forensic anthropology to medical and forensic science students including forensic mortuary practice students. her main area of research focuses on retention of anatomical knowledge through kinesthetic learning. , is an associate professor in human anatomy in the department of pharmacy and biomedical sciences, college of science, health, and engineering at la trobe university, bendigo, vic, australia. he is a discipline leader across the university campuses and teaches anatomy to a variety of students including physiotherapy and biomedical sciences. anneliese k. hulme, m.chiro., m.res., is a lecturer in the department of anatomy at the university of new south wales in sydney, australia. she teaches anatomy to medical and science students. her main research interest is in medical education.ian p. johnson, ph.d., is a professor of anatomy in the department of biomedical sciences, faculty of medicine, health and human sciences at macquarie university in sydney, nsw, australia. he is involved in undergraduate science and postgraduate medical education and his research is in neuroscience and medical education.amanda j. meyer, ph.d., is an anatomy lecturer in the school of human sciences at the university of western australia. she teaches neuroanatomy, histology, and gross anatomy to science, biomedical and medical students. her research focuses on the student experience (particularly anxiety and motivation) of anatomy learning. john w. morley, ph.d., is a professor of anatomy and cell biology and the deputy dean in the school of medicine, western sydney university, australia. his main area of teaching is topographical anatomy and neuroanatomy. his research is in sensory neuroscience (vision and touch), cns involvement in duchenne muscular dystrophy, and the development of visual prostheses. peter j. shortland, ph.d., is an associate professor of human anatomy in the school of science at western sydney university, australia. his main area of teaching is neuroanatomy but he also contributes to anatomy courses in musculoskeletal anatomy. his research is on the neuroanatomical plasticity that occurs in the spinal cord following nerve injuries, chemotherapy treatment or ingestion of toxic compounds that contribute to neuropathic pain.goran Štrkalj, ph.d., is an associate professor in the department of anatomy education, school of medical sciences at the faculty of medicine, university of new south wales, sydney, new south wales, australia. he teaches anatomy and biological anthropology to science and medical students. his main research interests are in human variation and evolution, history of science, and medical/science education.mirjana , is an associate professor in the medical school, college of health and medicine at australian national university, canberra, act, australia. she leads the medical school technology-enhanced learning and teaching team. her research encompasses anatomy and its clinical application in a variety of contexts and she teaches anatomy to medical and science students. stephanie j. woodley, b.phty., ph.d., is an associate professor in the department of anatomy, school of biomedical sciences, university of otago, dunedin, new zealand. she teaches anatomy across a variety of undergraduate and postgraduate science and health science programs. her research is focused on musculoskeletal anatomy and imaging, and its application to clinical practice. michelle d. lazarus, ph.d., is an associate professor and deputy head (education) of the department of anatomy and developmental biology at monash university in melbourne, victoria, australia. she is also director of the centre for human anatomy education at monash university. her research focuses on exploring anatomy education curricular impacts on medical student professional identity and role formation. key: cord- -eqpx dnq authors: south, nigel; brisman, avi title: remembering roger matthews ( – ) and editors’ introduction to “new times” and “environmental crimes” date: - - journal: crit criminol doi: . /s - - -y sha: doc_id: cord_uid: eqpx dnq nan of the key staff, with john lea, jock young and others, teaching on the pioneering ma in deviance and social policy. this was one of the first graduate level qualifications in critical criminology in the united kingdom (or anywhere) and an inspiring experience for many. as john pitts remembers, "roger (and jock) taught me how to think: it was (quite literally) life changing. roger was very encouraging, albeit not in the usual way. he would just say things like 'we're doing this book on "such and such"; you can do the chapter on youth justice.' this was terrifying, but after numerous impromptu discussions in pubs and restaurants around islington, the job would finally be done." roger was able to help many others in similar ways, providing opportunities, building confidence and "just having time for people," as with the common study programme in critical criminology, to which he contributed for many years and where, as jayne mooney says, "he will be remembered for his wit, commitment and mentoring of students, staying up to talk to them way into the night." after moving from middlesex, roger held professorial positions at london south bank university and finally, from , at the university of kent. throughout this long career, he maintained that it was important that criminologists should have something of value to say that could be beneficial to a cause, useful for progressive policy, or inspiring for students and activists-and preferably all of the above. he was no fan of work presented in "language that is opaque and impenetrable" that was "inward looking," or "of interest to very few people outside academia" (matthews : ) . he revisited long-standing interests over the years, including communities and crime prevention; prostitution, policy and law reform (in , he was an advisor to the all-party parliamentary group on prostitution and the global sex trade); and critical penology (his book doing time: an introduction to the sociology of punishment (matthews ) became an internationally respected key text). roger also identified significant but under-researched criminological subjects, editing collections on informal justice (matthews ) and on privatization (matthews ) , and carrying out studies of armed robbery. after an initial project funded by the home office (published in ), the search for funding for a larger investigation showed how, characteristically, he could be very realistic and practical. the most obvious funders seemed to him to be those affected, so he approached the british bankers association and they duly supported the successful project that became matthews ( ) . not many critical criminologists could venture into the boardrooms at the heart of financial capitalism and walk out with a check. roger was a keen and sharp commentator on developments in criminological theory and also, of course, a major contributor to the shaping of the discipline through his writings on "realist criminology." a "left realist" perspective emerged from the middlesex group in an amazingly lively period for british criminology (see matthews b; mooney : - ), spurred, in part, by the election of the thatcher-led conservative government in , and the recognition that the left needed to engage with what hall ( ) called "the drift into law and order society." as roger wrote in his introduction to what is to be done about crime and punishment?, much "criminological investigation is poorly conceived and researched. … this material tends to be theoretically weak, methodologically inadequate and has little or no policy relevance" (matthews : ) . for roger, the lessons for a realist criminology were to avoid becoming so entrenched in theory that the real consequences of crime for ordinary people, particularly the working class and powerless, were forgotten. roger enjoyed meeting friends, students and colleagues around the world, most recently developing research links in latin america, but he remained always a north london local. he was a dedicated follower of the tottenham hotspur football club and enjoyed cars and driving: the title of one of his essays, "false starts, wrong turns and dead ends" (matthews a), echoes this and also reminds one of us (nigel) of roger at the wheel, on a post-conference overnight journey from bremen (germany) to london that probably should not have been attempted non-stop! he was down to earth, generous and supportive of others. as john lea recollects, he was "prolific in terms of advice, writing references, and helping to create opportunities. he was never one to 'pull up the ladder' for those who came after him." roger was fun, talented and good company-"a working class bon viveur," as john pitts remembers-and despite illnesses, always interested in social events, good food and music. john lea recalls that he was at one time a keen amateur jazz musician, with both of them attending jazz classes in the early s at the extra-mural department at goldsmiths, university of london: "i still have a memory of roger trying to get his tenor sax to make the right sound," says john. as john pitts notes, roger was "one of the most astute and original thinkers in contemporary criminology," and he will be greatly missed by many. one of his last pieces of work was published in open access form in this journal, appearing online first on march , . it seems only fitting, then, to begin this issue with this article. in "new times, new crimes: notes on the depillarization of the criminal justice system" (matthews ), roger draws on the work of foucault ( ) and his provocative argument that the modern criminal justice system should be considered in terms of a "triangulated" relationship between three structures or pillars-the prison, the police and the "criminal classes." from here, roger describes the subsequent "depillarization" of the criminal justice system, making the case for how each of these structures or pillars has become "seriously weakened." in this part, roger's incisive analysis of "the crisis of imprisonment" flows into a meditation on "the end of policing," followed by an important exegesis on "the decline of crime." the third part of "new times, new crimes: notes on the depillarization of the criminal justice system" contemplates three "new crimes"cybercrime, environmental crime and terrorism. here, roger examines how the strategies that have been and continue to be developed to respond to these crimes entail significantly different responses than those that had been traditionally employed to address "normal crime" and "street crime." roger concludes by thinking through how these developments have raised questions about the relationship between victims and offenders, as well as "the explanatory value of the existing array of criminological theory." roger urges us to consider "whether we are moving away from a system of "class justice" to a more diverse and extensive system of crime control." "or is it the case," he asks, "that the regulation of these new crimes will generate a new layer of intervention that will simply overlay and complement the existing system? in addition, will the traditional focus on crime be replaced by a preoccupation with security?" roger's closing observation is as insightful as ever: "there can be little doubt," he writes, "that that which we might call, the 'old criminology,' with its preoccupation with the poor and the propertyless, is undergoing profound mutation as new forms of transgression are coming to dominate aspects of social and political life, creating new dangers and risks in a world that appears, in many respects, to be becoming more unpredictable and ungovernable." we have organized the rest of this issue as an homage to roger by including articles that center on the second of roger's "new crimes"-"environmental crimes." while roger was not a green criminologist and while many of these articles do not make explicit reference to roger's work, roger was always adept at seeing connections where others did not and keen on drawing people with disparate interests together. it seems appropriate, then, to carry forward the ideas and spirit of "new times, new crimes: notes on the depillarization of the criminal justice system" with this group of thematically focused articles. the first two articles, "animals, women and terms of abuse: towards a cultural etymology of con(e)y, cunny, cunt and c*nt," by piers beirne ( ) , and "wildlife management, species injustice and ecocide in the anthropocene," by ragnhild sollund ( ) , focus on speciesism and related injustices to nonhuman animals. the next three articles-"water theft through the ages: insights for green criminology," by alexander baird and reece walters ( ) , "big fish, small pond: ngo-corporate partnerships and corruption of the environmental certification process in tasmanian aquaculture," by paul bleakley ( ) , and "tapping into environmental harm in brewing: an exploration of pollution and waste in beer production," by travis milburn and favian guertin-martin ( )-center on issues of water and wastewater. from here, we turn to three articles dealing with intensive land use(s): "seismic risks: a criminological analysis of european investment bank support for the castor project," by daniel beizsley ( ) , "farming intensification and environmental justice in northern ireland," by ekaterina gladkova ( ) , and "waste crime and the global transference of hazardous substances: a southern green perspective," by reece walters and maria angeles fuentes loureiro ( ). these are followed by three articles addressing ways of preventing, responding to or resisting environmental harm: "ecologically unequal exchange, transnational mining, and resistance: a political ecology contribution to green criminology," by laura bedford, laura mcgillivray and reece walters ( ) , "utilising principles of earth jurisprudence to prevent environmental harm: applying a case study of unconventional hydraulic fracturing for shale gas in the united kingdom," by jack a. lampkin and tanya wyatt ( ) , and "in and against the state: the dynamics of environmental activism," by olivia hasler, reece walters and rob white ( ). we conclude this issue with five book reviews of monographs or edited volumes on various topics of environmental crime and harm. water theft through the ages: insights for green criminology ecologically unequal exchange, transnational mining, and resistance: a political ecology contribution to green criminology animals, women and terms of abuse: towards a cultural etymology of con(e)y, cunny, cunt and c*nt seismic risks: a criminological analysis of european investment bank support for the castor project big fish, small pond: ngo-corporate partnerships and corruption of the environmental certification process in tasmanian aquaculture discipline and punish: the birth of the prison farming intensification and environmental justice in northern ireland drifting into a law and order society. london: the cobden trust in and against the state: the dynamics of environmental activism utilising principles of earth jurisprudence to prevent environmental harm: applying a case study of unconventional hydraulic fracturing for shale gas in the united kingdom privatizing criminal justice armed robbery doing time: an introduction to the sociology of punishment realist criminology introduction: towards a public criminology false starts, wrong turns and dead ends: reflections on recent developments in criminology realism and left idealism new times, new crimes: notes on the depillarization of the criminal justice system tapping into environmental harm in brewing: an exploration of pollution and waste in beer production finding a political voice: the emergence of critical criminology in britain wildlife management, species injustice and ecocide in the anthropocene waste crime and the global transference of hazardous substances: a southern green perspective key: cord- - o ffk y authors: veleva, vesela title: the role of entrepreneurs in advancing sustainable lifestyles: challenges, impacts, and future opportunities date: - - journal: j clean prod doi: . /j.jclepro. . sha: doc_id: cord_uid: o ffk y this paper examines the role of entrepreneurs in advancing sustainable lifestyles (sls) to address climate change and social inequity. it is based on empirical study of eight u.s.-based sustainable entrepreneurs, focused on reducing material consumption. while business has a key role to play, many large companies are unwilling to promote sls as this is contrary to their current business models which are focused on growing consumption and sales. this presents an opportunity for entrepreneurial companies with innovative business models who are passionate about sustainability and social impact, and better positioned to take risks and innovate. the research examined emerging business models for advancing sls, key success factors and challenges reported by the entrepreneurs, the social and environmental impacts of their actions, and the future opportunities for scaling up such practices. the study found that entrepreneurs are well positioned to address simultaneously environmental and social issues, however, they lack resources to effectively measure these impacts to demonstrate an overall positive benefit and strengthen their value proposition. promoting green attributes alone is not enough to change the behavior of most consumers. it is critically important to emphasize other benefits such as a product/service quality, time or cost savings, or social impact. social media, formal and informal sustainability networks, it, sustainability policies, and consumer awareness are key to developing viable business models and competitive strategies that are difficult to replicate. the study found that sustainable entrepreneurs often face “costly” sustainability actions and lack the power to change „the rules of the game“; for this they need to collaborate with other key stakeholders, including ngos, policy makers, and progressive companies. based on the research findings the author proposes a new framework for the role of sustainable entrepreneurs as civic and political actors who not only offer innovative products and services, but help educate and influence key stakeholders, develop informal sustainability ecosystem, and thus create momentum for policy changes. following the paris agreement in , many cities and nations globally have taken steps to achieve substantial cuts to their greenhouse gas (ghg) emissions by focusing on major sources of emissions: electricity, housing, and transportation. yet, global carbon emissions have continued to rise reaching a record of . billion tons in (mooney & dennis, ) , before sharply declining due to the covid- pandemic (le quere, ). one reason is that policymakers' ambitious plans do not account for indirect emissions closely aligned with lifestyles, such as the energy embodied in producing the food, buildings, or consumer goods and services made outside a city or a state's boundaries (so-called consumption-based emissions) (mont et. al. ; brown & cohen, ; southerton & welch, ) . a recent study in oregon, united states, showed that while sector-based ghg emissions in the state increased % between and , consumption-based emissions were up % over the same period (brown and cohen, ) . such outsourcing of emissions is not just creating the illusion of making progress, but it is also an issue of equity and justice, as more affluent households have greater carbon footprints. fifty percent of the world's ghg emissions have been attributed to the richest % (southerton & welch, ) . decarbonization and dematerialization of existing lifestyles and services, however, do not go fast and deep enough. research has shown that technological innovation alone cannot help addressing climate change (alfredsson et. al., ; cohen et. al. ) . there is an urgent need to lower the consumption of material goods, such as living in smaller homes, buying fewer disposable goods, consuming less read meat, and driving and flying less. to reach an % reduction of a city's ghg emissions or a carbon neutrality (such as the city of boston's goal for year ) will require more structural changes in the way people live and work. changing consumer lifestyles, however, is challenging as it requires to examine systemically the entire value chain and overcome a range of economic, institutional, cultural, and social barriers. business model innovation is increasingly seen as essential for advancing sustainable lifestyles (sls) such as using public transportation, renewable energy, adopting plant-based diets, reducing material consumption, and housing footprint (bocken and short, ) . such a transition will require a fundamental shift in the purpose of business and how value is defined by companies and society. it will require new innovative actors who can work with other key stakeholders to help solve environmental and social challenges (mont et. al. ; ghisellini et. al., ; murray et. al., ) . while business has a key role to play, many large companies are unwilling to promote sls as this is contrary to their current business models that are focused on growing consumption and sales (windsor, ) . further, logistical hurdles and risks associated with revamping of global supply chains, often prevent companies from adopting new strategies (york & venkataram, ) . these factors present an opportunity for entrepreneurial companies with innovative business models who are passionate about sustainability and social impact, and better positioned to take risks. entrepreneurs' niche experiments can provide valuable insights and social learning about the challenges and opportunities in advancing sls, as well as help build momentum towards enacting government policies that "change the rules of the game" to reward sustainable businesses mont et. al. ; windsor, ) . however, researchers have reported that majority of business model innovations fail and there is a need to better understand the challenges that entrepreneurs face (geissdoerfer et. al. ) , the impacts they create (horisch, ) and the role of sustainability networks in entrepreneurial success (davies & chambers, ) . more empirical research is needed to examine the different pathways towards sustainability transformation and how to translate customers aspirations into purchasing activities (schaltegger et. al. ) . this paper aims to address some of these research gaps and examine the role of sustainable entrepreneurs in advancing sustainable lifestyles by explore the following questions: what are some emerging business models for advancing sls and the role of value chain partners and social networks in ensuring success? what are the social and environmental impacts created by sustainable entrepreneurs and how do they measure and communicate these? what are the main challenges faced by sustainable entrepreneurs presently and how do they work to overcome these? what is the role of sustainable entrepreneurs in advancing sustainability transition? the paper is structured as follows: it begins with a literature review, illustrating the impact of personal consumption on climate change, current strategies to promote low carbon lifestyles and the role of sustainable entrepreneurs in such a transition. it then introduces the research method utilized and presents key findings from the cross-case analysis. the author then proposes a new framework for the role of sustainable entrepreneurs in advancing sls and concludes with discussion of the main lessons learned, research contribution, and implications for future policy, practice and research. despite the paris agreement to address climate change, signed by countries, global carbon emissions have continued to rise reaching a record of . billion tons in (mooney & dennis, ) . nineteen of the warmest years globally have been registered since , demonstrating a clear trend towards warming (nasa, ) . governments around the world have enacted a range of policies to address major sources of emissions: electricity, housing, and transportation. yet, such efforts will be insufficient to stop global climate change unless we address personal consumption and lifestyles (mont et. al. ; alfredsson et. al. ; brown & cohen, ; southerton & welch, ) . according to the u.s. environmental protection agency (epa) % of u.s. greenhouse gas (ghg) emissions are associated with the energy used to produce, process, transport, and dispose of products ( % of which are thrown away in months) (u.s. epa, ) . a recent analysis of major cities worldwide revealed a % increase of those cities' carbon footprints when using consumption as opposed to production-based accounting (c , ). while much of the world still needs further development and consumption to reduce poverty and hunger, developed countries must reduce their consumption to address climate change and social inequity. wealthier countries such as finland and japan, for example, have three to five times higher lifestyle carbon footprints compared to poorer countries like brazil and india (lettenmeier et. al., ) . in the european union, total material consumption is estimated at - tons per year, compared to a sustainable level of tons per capita per year (mont et. al. ) . the need to address individual consumption and unsustainable lifestyles was first recognized in in agenda but has received limited attention by policy makers and other stakeholders until recently (mont et. al. ) . sustainable lifestyles (sls) are seen as an alternative to the current consumption-centered lifestyles and defined as "a cluster of habits and patterns of behavior embedded in a society and facilitated by institutions, norms and infrastructures that frame individual choice, in order to minimize the use of natural resources and generation of wastes, while supporting fairness and prosperity for all" (unep, ) . a recent unep framework for sustainable living defined five core areas for taking actions at the consumer level: housing, mobility, food, consumer goods, and leisure (unep, ) . a shift toward more sls has the potential to drive greater economic equality, open new business opportunities, and improve quality of life. for instance, telework helps improve employees' wellbeing and engagement; plant-based diets improve health outcomes; preventing waste (from surplus food or consumer goods) is associated with financial and time savings; smaller houses are more affordable. three main types of strategies have been used to address personal consumption and advance sls: a) education and awareness about the impacts of individual actions on climate change; b) policies to reduce consumption and change consumer behavior, and c) innovative business models to reduce or modify consumption. while environmental awareness and concerns about climate change are growing , few people understand their personal contribution or what actions they can take. a recent study found that % of americans are willing to change their behavior to reduce environmental impacts (nielsen ) but % of people do not know their carbon footprint or how to lower it (grinstein et. al., ) . in a recent study cordero et. al. ( ) measured the impact of a year-long university course about climate change and found that participants reduced their individual carbon footprint by . tons of co per year five years later. the authors argue that if applied at scale such education programs "would be of similar magnitude to other large-scale mitigation strategies, such as rooftop solar or electric vehicles." other studies have found that education is necessary but not sufficient to change consumer behavior due to the gap between individuals' aspirations and actions. even in countries with strong culture for environmentalism, a small share of consumers buy sustainable products (vringer et. al. ) . often it is believed that consumers are "free" to make a choice, but research has identified a range of barriers, from simple (e.g., price, availability and quality) to more complex (social, institutional, and economic). for instance, public transportation may not always be available, or it could be inconvenient. while biking has been promoted as healthier alternative to driving, ensuring bike safety remains a challenge in many communities. telework can help reduce individuals' carbon footprint and is linked to increased well-being and productivity (gimenez-nadal et. al. ) but it requires adoption at an organizational level. consumers also face a range of social and moral dilemmas ; vringer et. al. ( ) found that people are often reluctant to impose constraints on others. addressing such economic, institutional, and moral barriers requires government interventions such as new taxes, subsidies, disclosure mandates, or bans. most research on sls to date has focused on policy initiatives. southerton and welch ( ) analyze different policy approaches for changing individual behavior -from pricing, to information (education), use of social marketing campaigns, and infrastructure development (e.g., for mobility). they argue that while there are many successful examples of effective policies, more must be done to address the social, cultural, economic, and material barriers for reducing consumption. they call for "radical policy experimentation" and an "open debate and dialogue at local, regional, national and international levels that directly tackle consumption and visions of future ways of life." such radical approaches include j o u r n a l p r e -p r o o f promoting "time affluence" (as alternative to material affluence) and reducing the working week. such an approach, however, is problematic for many working-class employees, who need overtime hours to meet their basic needs (lautsch and scully, ) . the literature on sustainability clusters has identified the importance of supporting infrastructure and other local factors in promoting productivity, innovation, and competitiveness (maskell and malmberg ; martin and mayer ; porter and kramer ) . resilient clusters include not only the local businesses but also institutions such as schools, universities, trade associations, and non-profit organizations. local governments can play an important role in promoting cluster development and firm competitiveness by setting clear and measurable social goals and enacting relevant policies to promote social development and business sustainability (deutz and gibbs, ; veleva et. al. ) . in their "shared value" framework porter and kramer ( ) emphasize the "profound effect" of a business location on a firm productivity and innovation, which remain understudied by researchers. they argue that "shared value helps uncover new needs to meet, new products to offer, new customers to serve and new ways to configure the value chain, where the resulting competitive advantage will often be more sustainable than conventional cost and quality improvements". other researchers have examined shifting to sustainable consumption through the lens of the social change theory (cohen et. al. ) . sustainable consumption is defined as "the use of goods and services that respond to basic needs and bring a better quality of life, while minimizing the use of natural resources, toxic materials and emissions of waste and pollutants over the life cycle, so as not to jeopardize the needs of future generations" (norwegian ministry of environment, ) . in the current capitalist economy where consumption is seen as key to economic success, changing the dominant "regime" is challenging and more likely to happen gradually through incremental changes "in the fractures of the dominant system, in niches where they do not seem to pose any immediate threat to dominant classes and institutions" (cohen et. al., ) . more generally, the literature on sustainability transitions, degrowth, and steady state economy, has called for national-level policies to overhaul our current economic system to ensure more sustainable production and consumption (jackson, ; cosme et. al. ; cohen et. al. ) . this approach, however, is outside the scope of the current study. new business models a business model is about how an organization creates, delivers, and captures value (or in simple words, how it makes money). in this paper, we define "business model" using three main elements: the value proposition, value creation and value capture. sustainable business models are distinct in their focus on analyzing and communicating a sustainable value proposition to customers, in how they create and deliver value, and how they capture value while also maintaining or regenerating natural, social and economic capital (schaltegger et. al. ) . business model innovation, on the other hand, is more challenging to define. it typically does not require inventing new products, technologies, or markets, but instead involves changing the revenue stream, synchronizing the time horizons, or integrating the incentives (girotra & netessine, ) . for instance, leasing instead of selling solar panels was a major business model innovation which enabled overcoming the upfront costs for customers and thus led to expansion of the market for solar energy. developing long-term relationships with suppliers, customers and other partners along the value chain, can help companies co-create value, and thus generate competitive advantage. recent empirical study of centers for urban remanufacture in europe found that majority of examined initiatives were dependent on external support, and were not financially viable (ordonez et.al., ) . the researchers concluded that entrepreneurial innovation was needed to make the business j o u r n a l p r e -p r o o f case, and recommended launching business incubators in the area of reuse and remanufacturing. companies are increasingly seen as playing an important role in changing consumer behavior "through marketing and branding, new business models and choice editing" (bocken, ) . bocken et. al. ( ) introduced eight sustainable business model archetypes, described as businesses that a) maximize material and energy efficiency, b) create value from waste, c) substitute with renewables and natural processes, d) deliver functionality rather than ownership e) adopt a stewardship role, f) encourage sufficiency, g) re-purpose the business for society/environment, and h) develop scale-up solutions. bocken and short ( ) introduce the concept of "sufficiency-based business models" where companies deliver sustainability by "reducing absolute material throughput and energy consumption associated with provision of goods and services by moderating end-user consumption and encouraging consumers to make do with less." key enablers for companies' success with such business models include: strong focus on customers, commitment to go against the business-as-usual trends, performance and incentive systems aligned with sustainability objectives of the firm, strong focus on quality and durability, and radically different marketing campaigns. freudenreich and schaltegger ( ) examine sufficiency-oriented business models in the clothing industry and report that innovations such as service-and sharing-oriented businesses can be successful and help address both social and environmental problems in the clothing sector. however, legislation and policy intervention are often needed to bring such niche practices to the mainstream (bocken & short, ) . this confirms previous findings by that besides b corporation and social entrepreneurs, most profit-oriented corporations "cannot be expected to solve climate change and other environmental problems without changes in government incentives for business. " geissdoerfer et. al. ( ) further report the designimplementation gap in sustainable business model innovation which leads to market failure. the role of sustainability entrepreneurs in advancing sls there is a growing body of research on the role of entrepreneurs in addressing sustainability challenges. thompson et. al. ( ) provide one of the most comprehensive analysis of the similarities and differences between social, environmental and sustainable entrepreneurs. while all three are similar in their mission-driven business strategies, they also differ. social entrepreneurs are primarily focused on their social mission related to helping people. environmental entrepreneurs focus "on environmentally-relevant market failures" and seek to deliver both economic and ecological benefits. sustainable entrepreneurs aim to deliver longterm benefits across a "triple bottom line" or create simultaneously environmental, social and economic benefits (thompson et. al. ) . for the purposes of this study we will focus on sustainable entrepreneurs with the recognition that there is an overlap between the three types and environmental entrepreneurs are a sub-category of sustainability entrepreneurs (thompson et. al. ) . according to york and venkataraman ( ) entrepreneurs are best positioned to solve complex problems and turn uncertainty into business opportunity with social and environmental benefits as they are willing to take risks and innovate. bocken and short ( ) demonstrate that while startup businesses may not be economically viable initially, this can change over time because of regulatory action or changes in the market. even though entrepreneurs have limited resources and reach, their ability to foster strategic partnerships with large players can stimulate disruptive innovation, leading to industry transformations in sustainable development. pacheco et. al. ( ) demonstrate how sustainable entrepreneurs are able to change the "rules of the game" or the competitive landscape, by "proactively devising and influencing the establishment of new industry norms, property rights, and government legislation that transform the payoffs of their competitive games". examples of such industry transformations include the fair-trade movement, leadership in environment and energy design (leed) for buildings, and benefits corporation (b-corp) certification. according to entrepreneurs are able to "escape the green prison" or the disadvantages they face when pursuing costly sustainable actions, by either identifying opportunities within the current market system or "creating new opportunities through institutional changes that improve the competitiveness of sustainable behavior. " schaltegger et. al. ( ) take a co-evolutionary view of sustainability transformation by examining how pioneering business models can be scaled or replicated by startups and large companies (incumbents), leading to sustainable mass markets. haigh and hoffman ( ) report how hybrid organizations, defined as organizations at the interface between for-profit and nonprofit sectors that address social and ecological issues, are able to successfully challenge "the notion of trade-offs between economic, ecological, and social systems and instead create business models that develop synergies between them." the result is creating opportunities for "for-profit activities to be undertaken in ways that address sustainability issues." the authors demonstrate how hybrids challenge a) the existing beliefs about the social, ecological and economic system, b) the competitive practices, and c) how sustainability is enacted. firms focused on new business models for sustainability, however, face many challenges. geissdoerfer et. al. ( ) report that numerous new business model innovations fail due to the inability to implement their ideas in practice. based on comprehensive literature review they identify seven categories of challenges: a) balancing a triple bottom line, b) mind-set challenges, c) lack of resources, d) difficulty integrating technology with business model innovation, e) engaging in external relations, and f) lack of effective sustainability-focused business modelling methods and tools. the authors call for additional research on the challenges that business model innovation faces and the reasons for the low success rates. future studies should help understand: a) the implementation of the business model innovation process, b) its tools, and c) its challenges (geissdoerfer et. al. ) . veleva and bodkin ( ) report that top challenges for both entrepreneurs and large companies focused on waste reduction and circular business models include the lack of regulation and incentives, the lack of data and indicators to measure and communicate impacts, and the cost of product or waste take-back. entrepreneurs face additional challenges such as lack of brand awareness and market demand, access to financing, mentorship, networks, and the complex product or packaging design that prevents proper repair or recycling. the economic viability of secondary supply chains (focused on product reuse or remanufacturing) can be a key challenge due to the cost of recovering products and materials (freudenreich & schaltegger, ) . entrepreneurs also face the challenge of effectively communicating their sustainability impacts (horisch, ; holt & littlewood, ) . more broadly, entrepreneurs focused on creating new opportunities "may be limited by the opposition of other interested parties' with powerful political influence who may "impair entrepreneurs' ability to promote new institutions" . overcoming these challenges often requires that entrepreneurs look beyond their industry peers to form relationships with environmental, economic development or other civil organizations . policy makers, are key for supporting the growth of start-ups by providing subsidized loans and other legal infrastructure to internalize existing externalities (horisch, ). being able to achieve positive environmental and social impacts is at the core of the business model for sustainability for entrepreneurs and how they differentiate from competitors. at the same time, holt & littlewood ( ) find that most entrepreneurs are not effectively measuring and capturing such impacts. to address this challenge, they offer a framework for identifying, mapping and building indicators of impact for hybrid organizations. the authors further acknowledge that both positive and negative impacts may arise from entrepreneurs' activities and these must be clearly identified and addressed. often there are trade-offs between the environmental and social impacts. measuring and reporting impacts is challenging due to its complexity and lack of resources, even though it is critically important for "fostering stronger relationships between hybrids and external stakeholders including customers, beneficiaries and communities, international donors and supporters, and managers in traditional businesses" (holt & littlewood, , p. ) . horisch ( ) also reports that "sustainable start-ups face the challenge to communicate the sustainability effect connected to their products and services." without communicating both the direct and indirect impacts, they are unable to put pressure on established competitors or standard-setting organizations in order to change consumer expectations and prevailing norms (horisch, ). more broadly, however, the assessment of social and environmental impacts is challenging because it is based on personal values, beliefs and priorities. in his analysis of the socio-technical transitions to sustainability, geels ( ) raises the question of who should choose between multiple "green" pathways and establish the criteria for the choice? one option is for government to do so with the assistance of technical experts; the second one includes a more inclusive group of stakeholders, society groups and the public. in both cases it is important for entrepreneurs to be part of this process to gain legitimacy and public support, since these are key for securing financial investments and supportive policies (geels ) . similarly, costa & pesci ( ) find that effective metrics must be defined and constructed in an open dialogue with all relevant stakeholders; that there is "no single "gold standard" of measurement but instead a variety of metrics which reflect local goals, needs and stakeholder demands. using social network theory, neumeyer et. al. ( ) demonstrate that entrepreneurs' degree of connectivity with key stakeholders and access to different types of networks is key for their success. oskam et. al. ( ) introduce the concept of "value shaping" which refers to the "mutually constitutive process in which on the one hand networking helps to refine and improve the overall business model and on the other hand an improved business model spurs expansion of the network." the authors identify five micro-level processes through which value shaping happens: ideation, conception, business start-up, early growth and continued growth. they report that redirecting value and extending value are influenced by network interaction and are a critically important step in creating value for multiple stakeholders. other researchers have also demonstrated that "transformation to sustainable practices is an incremental and co-evolutionary process requiring collective action among actors, including but not limited to sustainable entrepreneurs" (divito & bohnsack ; schaltegger et. al. ) . horisch ( ) uses the multi-level perspective (mlp) as theoretical framework to examine the role of entrepreneurs in sustainability transitions. according to the framework developed originally by geel ( ), societal transitions "result from interaction processes between three different socioeconomic levels, which build a nested hierarchy: micro level niches, meso-level regimes and macro-level landscape" (horisch, ). start-ups are important actors primarily at the niche level, although they can play a role at the mesolevel. their role, however is currently underexplored. based on literature review horisch ( ) identified two ways in which entrepreneurs can advance sustainability transitions: j o u r n a l p r e -p r o o f through their market impact and through their sustainability effect. sustainability entrepreneurs must first create products and services with positive societal impacts and then distribute these "as widely as possible to develop a large overall sustainability effect and a significant contribution to sustainability transitions." this, however is challenging as start-ups either have limited resources to expand or are restricting their growth to stay true to their mission. regardless, start-ups can influence other important actors at the meso-level, such as large companies (schaltegger et. al., ) , public authorities and standardizing bodies (e.g., the international organization for standardization) which are critically important for changing regimes and advancing a societal transition. our understanding of the sustainable entrepreneurial ecosystems and how it leads to change, however, is still limited, according to neumeyer et. al. ( ) , who call for further research into four areas: a) how environmental, social and economic value is created in a community or a region, and the role of key stakeholders; b) what are the formal and informal rules for being part of a sustainable entrepreneurial ecosystem; c) how can success be defined and measured, and d) what is the role of emerging online social networks in advancing sustainable business models. schaltegger et. al. ( ) call for more empirical research on the different pathways taken by sustainable niche pioneers and other market actors, and the challenges and opportunities they face. ludeke-freund ( ) integrates two major perspectives about the role of entrepreneurs -agency perspective and systems perspectiveand calls for more empirical research to examine "if and how sustainable entrepreneurs can unfold agency within given systems such as industries and markets" and "if and how sustainable entrepreneurs actually use their business models to benefit from public policies." this study aims to address some of these research gaps, by examining sustainable entrepreneurs' business models, created impacts, current challenges and how they work with key stakeholders to overcome these and advance a shift to more sls. this study is based on interviews with eight u.s.-based entrepreneurial companies focused on reducing material consumption and promoting sls. the sustainable entrepreneurs in the study included box save, fixit clinic newton, food for free, irn surplus, joro, preserve, project repat, and semi-new computers. they represent both for-profit and non-profit organizations from diverse sectors in different stages of development. data for each company was collected between december and may using two main sources: a) publicly available information from websites, case studies, and other publications, and b) in-depth, semistructured interviews with founders and senior managers. the interview protocol was developed based on a literature review. all interviews were audio-recorded and transcribed for accuracy. the empirical data was managed through cross-case analyses using methodology described in eisenhardt ( ) and eisenhardt & graebner ( ) . all collected data and information were aggregated and summarized in a table format to enable further analysis (see appendices a and b). to ensure validity and reliability of the qualitative analysis, as well as protect confidential information, each participating company was invited to review and provide feedback to the transcribed interviews and data analysis. the primary goal of the study design was to select a diverse group of companies in terms of maturity (measured by years in operation), type of business (for-profit or non-profit), and business model (selling products or services). all participating entrepreneurs were committed to delivering benefits across a "triple bottom line." the study focused primarily on business to consumer (b c) companies to gain insights about how participating entrepreneurs work to change consumer behavior and the key challenges they face in this process. the interview questions and case research explored the following: • what are some emerging business models for advancing sls and the role of value chain partners and social networks in ensuring success? • what are the social and environmental impacts created by sustainable entrepreneurs and how do they measure and communicate these? • what are the main challenges faced by the entrepreneurs and how do they work to overcome these? what is their role in the transition to sls? detailed descriptions of the cases are provided in appendix a and include each company story and current activities. appendix b summarizes the key findings for each participating company in four areas: a) business model and value proposition, b) social and environmental impacts, c) key challenges, and d) future opportunities for scaling up sustainable business models. study participants reported a range of factors behind their business success such as increasing awareness about climate change and other environmental and social problems, strategic partnerships along the supply chain, sustainability policies, it, and quality customer service, confirming previous findings (dean & mcmullen, ; bocken & short, ; veleva & bodkin, ) . growing consumer awareness and willingness to take action were reported as important enabler by food for free, joro, preserve, semi-new computers, and irn surplus, confirming findings by cordero et. al. ( ) . "people are paying more attention to sustainability. i see the momentum, especially in the last few years. some of it is related to culture, some to regulation," according to sasha purpura, executive director of food for free (veleva & smith, ) . sustainability-focused public policies directly or indirectly support their business models. for instance, the massachusetts organics ban in and the higher waste disposal fees have benefitted food for free, preserve and irn surplus. the city of newton's policies to reduce waste and increase reuse are key for the launch of fixit clinic newton. analysis of the eight cases revealed that strategic long-term partnerships along the value chain are a key part of each entrepreneur's business model (see table ). for instance, semi-new computers' partnership with harvard university and large corporations provides continuous source of surplus computers for refurbishing and resale/donation. joro's partnership with a carbon offset organization provides opportunities for revenue generation. for recycling company preserve, partnerships with materials processors ensure a continuous supply of raw material (post-consumer polypropylene), where its partnerships with retailers such as whole foods and target ensure a sales channel. food for free's partnerships with grocery stores and universities ensure access to fresh, healthy food, while its partnership with cities provides funding and access to people in need. furthermore, all participating entrepreneurs are part of an informal ecosystem of sustainable businesses and other stakeholders who act as suppliers, customers, or strategic partners (e.g., food for free and the town of cambridge, box save and monoflo, fixit clinic and green newton, preserve and stonyfield farm, plum organics and ocean plastics initiative). such networks, while informal and underdeveloped, provide competitive advantage and ensure entrepreneurs stay true to their sustainability mission. this finding is in line with neumeyer & santos' ( ) research about the importance of social capital and access to different types of network actors for launching a sustainable business model. the geographic location (massachusetts, usa) was also reported as key factor for entrepreneurial success, confirming previous research on the importance of a specific location for providing supportive culture, capital and other resources, as well as allowing to quickly respond to customer needs and gain trust and legitimacy (neumeyer et. al. ; porter & kramer, ) . in all cases technology enables companies to optimize logistics, reduce the costs of storing and shipping (e.g., box save, irn surplus), leverage low cost marketing (e.g., preserve, joro, box save, and project repat) and educate customers (joro, food for free). with exception of semi-new computers, all entrepreneurs use online social networks such as facebook, twitter, instagram, linkedin, you tube, and others (see table ), which they see as critical for their business success. this finding confirms previous research by correia et. al. ( ) on the role of social networks and mobile technologies in building competitive advantage by providing a new way to expand business, adapt to new consumers, turn fans into customers, and develop tacit organizational knowledge about virtual communities which is hard to replicate (correira et. al., ) . the research also confirmed previous findings about the importance of having a strong focus on customers, building long-term relationships, providing some incentives, and making it easy for consumers to act (bocken & short, ; bocken ( ) that entrepreneurs (and sustainability entrepreneurs in particular) are best positioned to solve complex problems and deliver social and environmental benefits. in addition to addressing waste and ghg emissions, participating entrepreneurs create positive social impacts such as developing new skills (fixit clinic, semi-new computers), reducing food insecurity (food for free), saving time (box save, irn surplus), and improving health (joro, food for free), in addition to creating local jobs. moreover, several participating entrepreneurs reported their social impacts as key for differentiating from competitors. while for companies like joro educating and empowering consumers to address climate change is at the core of their business model, other study participants emphasize cost or time savings, revenue generation, social impacts, and/or outstanding customer service. as one of the interviewees summed it up, "green attributes do not always lead to sales," confirming previous findings by esty & winston ( ) . all study participants reported lack of resources to more effectively measure the environmental and social impacts of their products and services. while some included specific indicators such as amount of products/waste repurposed or people served, these typically measured outcomes and not overall impacts such as greenhouse gas emissions prevented, skills developed, or time and dollar saved. for instance, irn surplus provides its customers with individualized reports which describe the outcomes and some impacts, but the latter are often qualitative or measure outputs, versus impacts. for example, for one of its customers -kent place school in summer, new jersey -irn surplus leveraged its network and partnership with steelcase to locate a nearby recipient -habitat for humanity restore in bucks county, pa, about miles away. the company reported several key impacts from the project: a) the school's ability to uphold its commitment to sustainability and reuse or recycle more than . tons of furniture without paying more than for disposal; b) steelcase's ability to uphold its commitment "to providing environmentally sustainable products and services throughout the lifecycle of steelcase products," and c) dozens of families who benefitted from obtaining "high-quality, low-cost furnishings through the habitat restore, or living in the habitat homes that restore revenues help to build." (irn surplus, ) . food for free measures the amount of surplus food repurposed (in pounds) and the number of meals distributed. in it helped rescue million pounds of food and feed over , people (veleva & smith, ) . the company, however, is unable to estimate the ghg gas emissions prevented from food rescue compared to composting or disposal, or the dollar savings and improved health outcomes for people having access to fresh, healthy food. similarly, fixit clinic newton measures the number of participants and products repaired but is unable to track and report the environmental and social impacts such as increased awareness of environmental problems, reduced ghg emissions and waste, new skills development, time to repair a product, or dollars saved. for many people the lack of time often leads to buying new products instead of repairing an old one, a sustainability challenge reported previously in the literature (southerton & welch, ) . better measurement would not only help strengthen entrepreneurs' value proposition among early adopters as reported by veleva & bodkin ( ) but is also crucial for evaluating potential trade-offs and demonstrating an overall positive impact. for instance, box save estimates that when comparing cardboard boxes to reusable crates for users, manufacturing of the former generates , % more co (not including shipping for landfill or recycling) (donovan, ) . this estimate, however, does not reflect the fact that cardboard is made of renewable resource, while polypropylene is derived from fossil fuel. preserve's move to compostable single use products could help reduce the ghg emissions from collecting and recycling post-consumer polypropylene. however, recent studies have warned about potential presence of highly toxic per-and polyfluoroalkyl substances (pfas) in compostable products, a class of over , fluorinated chemicals that persist in the environment for a long time, and are associated with cancer, developmental toxicity, immunotoxicity, and other health effects (cpa, ). furthermore, compostable containers require special facilities for handling (e.g., anaerobic digesters), which may not be available locally, potentially leading to landfill disposal or incineration, both associated with release of ghg emissions (veleva & smith, ) . while semi-new computers is committed to prevent waste and ghg emissions while closing the digital divide by sending refurbished computers to nigeria, ghana and sierra leone, they have been criticized for potentially contributing to the growing e-waste crisis in africa (clark & clark, ) . in addition, shipping computers to such far destinations contributes to climate change and air pollution. without proper life-cycle analysis and measurement of the overall social and environmental impacts of their business, it is not possible to confirm the overall positive impact. these findings illustrate the importance of developing and using effective indicators to measure and evaluate the social and environmental impacts at a company or product/service levels. previous research has found that even large companies within the same sector using standardized indicators, report inconsistent and vastly different measures focused on outputs rather than impacts (veleva et. al. ) . aggregating different measures to identify an overall impact is challenging as it reflects a variety of assumptions, local issues, and personal values, therefore must include other stakeholders affected by such practices. this confirms research by costa & pesci ( ) that effective metrics must be defined and constructed in an open dialogue with all relevant stakeholders; that there is "no single "gold standard" of measurement but instead a variety of metrics which reflect local goals, needs and stakeholder demands (costa & pesci, ; matzembacher et. al. ). deven's eco-industrial park provides one example of how a multi-stakeholder process can be leveraged to develop locallyrelevant sustainability indicators, which can serve as a valuable tool to raise awareness, promote transparency and accountability and guide local policies towards established goals and targets (veleva et. al. ) . despite their success to date, study participants reported numerous challenges in scaling up operations (see appendices a and b). while all of them offer competitive pricing, they often cannot compete with inexpensive imports from china based on cost alone (e.g., preserve, semi-new computers, project repat). to stay true to their mission, many face costly sustainable actions, such as using sustainable packaging, eco-friendly materials, or recycling waste instead of sending to landfill (e.g., project repat, food for free, box save, preserve, semi-new computers). this confirms previous findings that entrepreneurs are often at competitive disadvantage when pursuing new sustainable business models ludeke-freund, ) . all entrepreneurs report insufficient funding and other resources (space, transportation, storage, volunteers) as a key challenge. non-profit organizations such as food for free and fixit clinic rely on grants and volunteers to support their work; others such as box save, semi-new computers, project repat, joro, and preserve, capture value based on customers' willingness to pay for a product or service that is high quality, good value or socially and environmentally responsible. all entrepreneurs in the study reported not having the capacity to effectively measure and communicate the social and environmental impacts of their products and services which could strengthen their value proposition. these findings confirm previous research on the barriers faced by companies advancing new business models to reduce consumption bocken & short ; veleva & bodkin, ) . the lack of brand awareness was another challenge faced by most entrepreneurs, especially the "younger ventures" such as box save, joro, project repat and fixit clinic. some reported lack of consumer awareness about how to act to address sustainability challenges (joro, fixit clinic, box save), while others reported a gap between consumer aspirations and actions (preserve, semi-new computers). this confirms previous findings that consumer education is necessary (grinstein et. al. ) but not enough to change behavior (vringer et. al. ) . social media could be leveraged further to help consumers overcome some of the social and moral dilemmas reported in the literature (vringler et. al. ) . study participants also reported the need to raise awareness about the environmental and social impacts of reuse versus recycling and disposal in order to change the evaluation criteria used by customers, confirming previous research by veleva & bodkin ( ) . customers' lack of time was reported as a barrier by some participants (e.g., fixit clinic newton, preserve, joro) but was leveraged as opportunity by others (e.g., box save, food for free, irn surplus). the heightened awareness and interest by young people to take sustainability action and increasing local sourcing and zero waste commitments by cities and companies are expected to support future sustainable entrepreneurs. in addition, as reported by windsor ( ) "businesses, consumers and institutions (government and others) "are likely to face increasingly volatile, uncertain, complex, and ambiguous conditions in the future". the covid- pandemic, for instance, is expected to accelerate the shift towards more local and regional production and consumption, leading to reduced ghg emissions from transportation and new opportunities for sustainable entrepreneurs (mckinsey, ) . all sustainable entrepreneurs in the study see the lack of government policies such as carbon tax, bans on disposal of certain products, mandating design for repair, or a full-cost accounting, as the greatest barrier for scaling up their businesses but also the greatest opportunity in the future which confirms previous research (caldera et. al. ; veleva & bodkin, ) . for instance, a carbon tax (or a tax on raw materials) would make preserve products and box save services more price competitive. bans on landfill disposal of furniture and other products, would help create markets for reuse and recycling and support entrepreneurs such as irn surplus. the massachusetts organic waste ban for example, has led to significant growth in entrepreneurial companies focused on food rescue and composting, and measurable economic and social benefits (icf, ) . adopting laws mandating design for disassembly and repair, could help expand the secondary markets for many products and support entrepreneurs such as semi-new computers and fixit clinic. introducing reporting requirements for waste similar to the city of boston building energy and disclosure ordinance (city of boston, ) can increase transparency about the amount of waste generated and create incentives for large organizations to seek alternatives to landfill or incineration. although entrepreneurial players in the study have been able to identify opportunities within the current consumption-based economic system, scaling up such niche experiments requires involvement of other stakeholders and policy action (dean & mcmullen, ; bocken & short ; southerton and welch, ; cohen et. al. ; horisch, ; ludeke-freund, ) . for instance, the proliferation of fixit clinics in the u.s. has attracted the support of politically-active public advocacy groups which are working with citizens and progressive policy makers to adopt new "right to repair" mandates at state levels (u.s. pirg, ). as of december , at least u.s. states had put forward digital right to repair bills; these however, were opposed by the $ . billion electronic industry, demonstrating the push back by powerful incumbents and the challenges in changing current regimes (allendorf, ) . transitioning to more sustainable consumption systems requires creation and reinforcement of a new path, as well as "destabilization of the existing path," according to heiskanen et al. ( ) . path dependence is defined as the self-sustaining characteristics of existing systems, while path creation relates to creating new paths by engaging various stakeholders and generating momentum and respectively, change (heiskanen et al. ) . environmental entrepreneurs are often seen as "agents of change" and "a major force in the overall transition towards a more sustainable business paradigm" (schaper ) . while they are more likely to pursue path creation in sustainable consumption systems, the latter requires significant resources, including financial and political power, which they often lack, as demonstrated in the current study. what entrepreneurs are able to do, however, is to educate and influence other stakeholders, advance informal and formal sustainability networks and thus create momentum towards new policies, norms, and institutions. for instance, food for free is able to influence both policy makers and large companies to secure resources, reduce food waste and advance new policies to change food expiration labels. preserve's business model has attracted the attention of some large companies such as berry and vdl: "there's something about what preserve has been doing that makes the larger companies interested in us. one example is with berry, a $ billion sales and $ billion in market cap. they work with the gimme program every year and they make that preserve to go container. our partner in europe is vdl [they make the mini cooper]. they are an ecofriendly/socially responsible business and they are huge." transition to more sustainable lifestyles requires collective action and collaborations among various stakeholders, including users, ngos, progressive large companies and policy makers. a truly sustainable future "requires system-based thinking that involves in equal measure, society, environment and economics" (murray et. al., ) and calls for new policies that reward sustainable behavior. based on the study findings and analysis, the author proposes a new framework for the role of sustainable entrepreneurs in advancing sustainable lifestyles (see figure ), which demonstrates that they are not only innovators but also civic actors supporting this transition. in collaboration with a range of stakeholders such as other sustainable entrepreneurs, large companies, ngos and policy makers, sustainable entrepreneurs launch innovative business models to advance sls. most of their business model innovations include social rather than technical experiments which provide valuable insights and social learning about the challenges and opportunities in changing consumer behavior. to succeed, sustainable entrepreneurs leverage strategic partnerships, social media, it, the growing sustainability awareness, and public policies, which help them identify opportunities within the current economic system. their main value proposition for consumers is based on offering cost or time savings, social benefits, education and empowerment to act; they also provide strong customer focus and quality service. with their business model experiments, sustainable entrepreneurs help create informal and formal sustainability network and influence key stakeholders such as large companies, ngos and policy makers. thus, they act not just as innovators but also as civic actors helping create momentum towards enacting government policies that "change the rules of the game" to reward sustainable businesses that help address climate change and social inequity. the current study confirmed many findings from prior research about sustainable entrepreneurs' ability to launch innovative business models to address complex issues such as climate change and social inequity. it also identified some key lessons learned by first movers. first, entrepreneurs are well positioned to address simultaneously environmental and social issues. however, they lack the resources to effectively measure related impacts to strengthen their value proposition and demonstrate an overall positive impact. such measures require working with other stakeholders and developing locally-relevant indicators reflecting existing challenges, needs and goals. second, environmental awareness has significantly increased in recent years and a growing number of people are willing to take actions to reduce their carbon footprint. educating and empowering such early adopters could not only support new innovative business models, but also help change prevailing social norms, if effectively leveraging social networks and strategic partnerships. third, promoting green attributes alone is not enough to change the behavior of most consumers. it is critically important to emphasize other benefits such as a product/service quality, social impacts, time or cost savings. this confirms previous findings by esty & winston ( ) that sale of green goods is difficult and "green" should be promoted as the "third button" after quality and cost savings. fourth, formal and informal sustainability networks, social media, and sustainability policies, are key to developing viable business models and competitive strategies that are difficult to replicate. finally, to avoid "costly" sustainability actions and change the competitive landscape, entrepreneurs need to reach out and collaborate with other key stakeholders such as policy makers, ngos, and citizens coalitions, in order to change "the rules of the game," such as the laws, institutions and social norms. without such actions their market and sustainability impacts will be limited. the study demonstrates that policymakers have a key role to play in advancing sls by a) adopting consumption-based ghg emission inventory and raising awareness about the impact of individual lifestyles on climate change; b) enacting effective regulations or eliminating regulatory hurdles to sls; c) providing incentives to companies engaged in such practices through taxes, subsidies, disclosure mandates, or bans on certain products or practices in order to "level the playing field"; d) providing financial support, networking and mentorship opportunities for sustainable entrepreneurs, and e) supporting development of enabling infrastructure, new institutions and norms that promote sls. local zero waste goals or waste bans, for example, can increase demand for alternatives to landfill disposal and incineration and thus act as powerful drivers for entrepreneurial innovation. improved city planning could advance the use of public transportation, bicycling, and walking, supporting entrepreneurs focused on mobility solutions such as bike and shooter sharing. enacting regulations that ban toxic chemicals from products and packaging, and mandating design for disassembly and repair, are crucial for enabling reuse of products and materials. policy makers can utilize tax incentives or subsidies to reward companies advancing more durable, low-carbon choices such as the swedish tax break for repaired products (orange, ) and the european union "right to repair" laws (right to repair, ). providing financial support to entrepreneurs and other organizations in the form of grants, low interest loans, or business incubators, is critical for supporting smaller companies as previously reported in the literature (lowitt, ; rizos et. al., ; ludeke-freund, ). in addition, government agencies could partner with non-profit organizations to help raise awareness about the importance of waste prevention and reuse versus recycling, by launching carbon footprint labels, awards, benchmarking studies or networks promoting sls. such networks should include a variety of stakeholders, such as entrepreneurs, progressive corporations, non-profit organizations, academics, policy makers, and citizens' organizations. they could work to develop a locallyrelevant vision for sustainable living, indicators to measure progress, and actions to drive change. the present study demonstrates that a growing number of sustainability entrepreneurs are experimenting with new business models to promote sustainable lifestyles. they are able to overcome existing challenges by leveraging the growing consumer awareness, value chain partnerships, it, social networks and sustainability-focused policies, to launch innovative products or services which offer time or cost savings, quality service, and a range of social and environmental benefits. in this process they help educate and influence other important actors such as ngos, large companies, and policy makers, confirming previous research by geels ( ) and ludeke-freund ( ) . sustainability entrepreneurs, however, are unable to achieve a market effect and a shift to sls on their own, which requires political support and new regulations. their role is to experiment with innovative business models, help create sustainability networks, educate and influence key stakeholders, and empower them to act. in this process entrepreneurs provide valuable insights and social learning which has largely been missing in the sustainability transitions literature primarily focused on technological innovations and solutions. scaling up entrepreneurs' experiments to achieve a market impact (horisch, ) , however, requires the collaboration of various stakeholders in order to advance better measurement, bold policy interventions, enabling infrastructure, and new social norms to promote sustainable living. policy makers in particular have a key role to play to internalize existing externalities and ensure sustainable entrepreneurs are not at competitive disadvantage, which confirms previous findings by ludeke-freund ( ) . the study has several limitations. first, it only included eight entrepreneurial companies. a future study should consider including a larger number of entrepreneurs within each of the five domains of sls to examine emerging drivers, challenges and future opportunities as seen by the participants. research can also focus on a specific sector to explore in greater detail emerging business models and how entrepreneurs work with policy makers and other stakeholders to define key sustainability goals, indicators, and strategies to change existing norms and institutions. another limitation was that participating companies were based in massachusetts, a state with high public awareness and support for environmental and social initiatives. a future study could consider comparing two different regions to examine the impact of environmental awareness and culture on entrepreneurial success. in addition, future research could include a multi-stakeholder study for a specific region to examine the role of social and cultural norms and institutions on consumer behavior. the main contribution of this research is that it demonstrates that sustainable entrepreneurs act as civic and political actors who not only offer innovative products and services, but help educate and influence key stakeholders, develop informal sustainability ecosystem, and thus create momentum for civil and political changes. the study examines the main challenges faced by sustainable entrepreneurs presently and provides key lessons learned about how to overcome these. it illustrates the need for implementing effective indicators to measure the social and environmental impacts of sustainable products/services, in order to evaluate potential trade-offs and ensure overall positive impact. the research confirmed previous findings about the ability of entrepreneurs to identify opportunities within the current market system. however, it demonstrates that sustainable entrepreneurs cannot change "the rules of the game" on their own. scaling up their business models to achieve market and sustainability impacts requires collaborations among various stakeholders and bold policy actions to change the incentives for consumers and companies. company story and business model box save: promoting reusable moving boxes box save was founded in by two entrepreneurs, paul benoit and doran donovan, who worked for years in the finance and software industry, respectively. they launched box save after exploring many ideas such as used book shops and used sporting goods' shops (they also visited a company renting reusable moving boxes in washington d.c. to learn about their experience). the firm's core business is to rent reusable moving boxes to households, businesses, nonprofits and government agencies in the greater boston area. the co-founders run their business with minimal expenses; they have eight part-time employees and one part-time driver (they also deliver boxes themselves). the employees work mostly on cleaning the boxes which are sanitized with ecofriendly cleaner after each use. according to co-founder donovan there are about firms in united states with similar business, but they do not compete as each operates in a specific geographic area; instead they connect via facebook to share ideas. box save initially struggled to get exposure, but in emerged on the top of the search results for greater boston. for every $ invested in marketing they get $ in revenue (they use facebook, yelp, google, and real estate firms). in their first year of operations box save saw % growth; in their sales were up % compared to the prior year . the company's reusable boxes are made of polypropylene and can be used up to times (or years) and then recycled. they are also manufactured in the u.s. by monoflo, thus reducing transportation impacts. cardboard boxes on the other hand are used once or twice and even when recycled use % of the energy required to make a new box (box save, ) . despite these environmental benefits, the company's main messaging and value proposition for customers focuses on time and money savings (they offer drop off and pick up of the boxes, flexible schedules) and the outstanding customer service. fixit clinic-newton: helping people repair products fixit clinic is a non-profit organization launched in in the u.s. by entrepreneur peter mui with the main goal to help people repair broken products and thus extend their useful life and prevent waste. the company was modelled after the repair cafe movement in europe with one main difference -fixit clinic uses volunteers and teaches people about doing the repairs themselves (repair cafes, on the other hand, use specialists to repair consumer products). it aims to help people develop critical thinking and repair skills while saving them money and teaching them about sustainable consumption. the concept has grown quickly, and hundreds of events have been held recently across united states hosted by municipalities, local governments, ngos, colleges, and public libraries (gulf coast makercon, ) . since design constraints can make it challenging to repair many products, supporters of the idea have advanced new right to repair legislative proposals in numerous states in the u.s. (repair.org, ). following the steps of other massachusetts communities such as cambridge and belmont, the city of newton held its first fixit clinic in june at the newton free library. organized by the newton recycling committee, the event brought in volunteers who helped attendees repair a variety of products such as jewelry, textiles, lamps, and vacuum cleaners, among others. the success of the event led to scheduling two more events and discussions about making the fixit clinic a more regular event for residents. at the same time, organizers admitted that the lack of time, volunteers and ability to repair many products limit fixit clinic's impact. food for free: turning food waste into healthy meals food waste is a major problem around the world and especially in the united states where % of food is lost at the retail and consumer levels (contributing to waste generation and climate change), while . % of u.s. citizens face food insecurity (usda, ) . to address these two problems, food for free, a small nonprofit company in cambridge, massachusetts, began taking surplus food from grocery stores and other organizations (which would otherwise be thrown out), and creating healthy meals for people in need. the idea for the company emerged in when a group of friends realized that local meal programs were struggling to provide fresh food for people in need, while supermarkets were throwing away large amounts of food they could not sell. this led to launching an organization which can "bridge the gap between waste and want" (food for free, ). food for free's most innovative program is the family meals, which began in as a partnership with harvard university after the company leadership realized that it was legal to donate cooked food. in food for free had full-time equivalent employees and about volunteers helping to prepare the meals, which are sent to schools and community colleges. food for free takes all food for free and gives it out for free, therefore it relies on funding from individuals and small businesses, foundation grants, and state and city contributions to support its work (e.g., their backpack program) (veleva & smith, ) . irn surplus: promoting reuse instead of recycling irn was launched as recycling company in . in it decided to shift its core business to focus only on reuse. this led to the change in its name to irn surplus. the idea about reuse emerged in when co-founder mark lennon began getting calls from colleges unable to donate all of their surplus products locally (irn, ). as a result, "irn ended up with thousands of pieces of furniture that the local environment couldn't absorb," shared lennon. to address this problem, the co-founders developed a national and international network of recipients. presently irn surplus is a privately held, for-profit firm with employees, which works with companies and universities interested in donating surplus products. the transition to reuse was a result of "evaluating the business environment and deciding that it doesn't make sense to compete with the big names such as casella, waste management and el harvey, but instead focus on their niche market of repurposing, where there is very little competition," explains lennon . irn surplus has three core commitments: a) to handle everything, b) to make reuse simple, and c) to make reuse cost effective (irn, ) . to be competitive, the company charges %- % less than the cost of waste disposal. they operate in a very efficient way; the generators and recipients split the cost of transportation and all companies they work with use their own labor to move the products. irn surplus does not use warehouse which helps reduce overhead, although for some clients they keep a few storage trailers. while the company is operating only as b b business, it sees great opportunities in the b c space and is interested in working with apartment complexes. joro: educating consumers to reduce their carbon footprint joro was launched in by sanchali pal and cressica brazier who sought to apply massachusetts institute of technology (mit) research to help address the complex problem of climate change. the company's main business model leverages an app which helps people measure and reduce their carbon footprint. on its website and app joro states: " if everyone improved their footprint by . % each year for the next years, we'd achieve the global paris climate targets to keep average temperature rise below . c. together, we can cut our emissions in half by " (joro, ). joro provides simple suggestions on how to achieve such reduction, from walking and biking less than miles, to taking public transit for distances less than miles, to limiting meat to one meal per day, or turning the thermostat down by ℉. in addition, consumers can buy carbon offsets. in joro conducted a beta pilot with , app users and reported that participants reduced their carbon footprint by % on average ( % of this reduction was result of behavior change and % a result of carbon offset). the top five behavior changes reported by joro active users included reducing meat consumption, cold water washing, walking and biking more, unplugging devices when not in use, and avoiding red meat (joro, ). preserve: upcycling plastics and offering plantbased products preserve is a privately-held company which is also certified as b-corp (benefit corporation), focusing not just on profits but also on delivering value for all stakeholders. it was founded in by entrepreneur eric hudson, who in the early s saw the waste problem and tried to solve it by focusing on recycling (preserve, ). in preserve had employees and some sales representatives. its core business involves taking post-consumer/post-industrial polypropylene (# ) plastic and upcycling it in a variety of reusable products -toothbrushes, cutlery, and containers. in it launched the preserve ocean plastic initiative (popi) with the goal to utilize high-density polyethylene (hdpe) plastic that was "headed for the ocean." recently it also began offering compostable single use cutlery in response to growing demand. its partnerships with retailers, companies, and materials suppliers ensure low cost, continuous supply of post-consumer/postindustrial polypropylene. preserve uses digital marketing to reach customers. while the company offers competitive pricing, mr. hudson shares "we don't offer premium price, but our price is higher. we seek to be parity priced with everything we do. our reusable plates are a little higher price than something that you'd find from china, and certainly more expensive than the disposable alternatives." preserve's business has grown over the years driven by increasing awareness of environmental problems and demand for reusable and compostable products. as of january , preserve's products sold in countries (an increase from just two years earlier). project repat: upcycling old t-shirts into blankets nathan rothstein and ross lohr started the company in with the goal to solve the problem of excess clothing via upcycling. "people do not realize that majority of donated cloths do not get reused or recycled", explained erin kizer, project repat chief operating officer. customers send their old t-shirts and project repat makes blankets from them and sends them back. the company has robust system for tracking orders and three local partners to make the blankets -precision sportswear in fall river, massachusetts, opportunity threads in north carolina, and open arms studio in texas (project repat, ). to reduce costs, they only sell online and use various social media platforms. a few years ago, they opened a store in newton, massachusetts, but found that e-commerce was a more effective platform for their type of business. as of project repat had four employees and operations in massachusetts, north carolina, and texas. to reduce the environmental impacts of shipping they use low carbon footprint bags to send the blankets and recycle all cardboard boxes from customers. they are committed to be zero waste company and send all their waste for recycling, which presently is costly and one of their big challenges. finding supply chain partners in the u.s. is another challenge as most of this work has been outsourced to asia. while the company's products provide social and environmental benefits (jobs, local manufacturing and waste prevention), in their messaging they do not focus on these but instead on the intrinsic value of the products. "we pitch it as a way to preserve value as people have emotional connection to old t-shirts. promoting environmental friendly choices doesn't translate to sales," explained kizer. semi-new computers: extending computers' useful lives via charlie thompson and marlene archer spent many years working in the computer industry before starting semi-new computers. in the s ms. archer was at boston computer society where members would match donations to non-profit organizations. often such donations included refurbished computers. when she began working at harvard university ten years later, she met the university sustainability director which led to the discussion about surplus computers. she found repair & refurbishing that harvard business school, for example, replaces all its computers every three years even though % of them are in excellent condition. the conversation led to launching a program to repair and donate surplus computers, which became known as semi-new computers (semi-new computers, ). over the years the two co-founders launched some innovative initiatives and partnerships. for instance, they developed a partnership with autistic students in lexington, massachusetts (part of a job readiness training), where the students helped clean and prepare the computers. funding for the training was provided by the native towns of the students ( towns participated) and harvard university provided the old computers. another innovative initiative was the bridge program, where semi-new computers trained harvard university employees who may not speak english well (e.g., janitors). the goal of the program was to teach such people basic computer skills and provide them with refurbished computers for use at home. according to mr. thompson, "this was very labor-intensive process; people didn't have internet access at home, they didn't know how to set up a computer. we had to send someone to help them." over the years the business has faced numerous challenges. initially they used to sell new and used computers (which they received from other large organizations in the boston area), but there was no significant difference in price and functionality (e.g., if -years old computer costs $ and a -years old is $ , people would just buy the new one). as a result, semi-new computers began sending refurbished computers to nigeria, ghana and sierra leone. software presents another major challenge with computer refurbishing, due to the constant upgrades and the cost of new software. as mr. thompson summed it up, "we had a vision to make boston a refurbished hub. right now it doesn't make sense to scale up as the economics doesn't work." as of the two co-founders were considered consultants to harvard university and their company was based at the harvard recycling center, although they continued to work with other universities and major corporations (semi-new computers, ). they were also actively volunteering at the cambridge fixit clinic to help people repair their computers and develop such skills among young people. the economics doesn't work (new computers are inexpensive); technological challenges (e.g., software does not work); lack of skilled people to repair electronics; lack of more space. policies to address planned obsolescence and tax waste generation and resource use (e.g., mandate design for disassembly; carbon and waste taxes) why achieving the paris agreement requires reduced overall consumption and production how big tech stopped right to repair in new york towards a sufficiency-driven business model: experiences and opportunities business-led sustainable consumption initiatives: impacts and lessons learned business model innovation climate-governance entrepreneurship, higher-order learning, and sustainable consumption: the case of the state of oregon evaluating the enablers and barriers for successful implementation of sustainable business practices in 'lean' smes building energy reporting and disclosure ordinance global e-waste: unintended consequences of marketing strategies necessitates a plan for change purchasing safer compostable food ware social change and the coming of post-consumer society: theoretical advances and policy implications integrating hybridity and business model theory in sustainable entrepreneurship americans increasingly see climate change as a crisis, poll shows the role of climate change education on individual lifetime carbon emissions social impact measurement: why do stakeholders matter assessing the degrowth discourse: a review and analysis of academic degrowth policy proposals what is disruptive innovation? toward a theory of sustainable entrepreneurship: reducing environmental degradation through entrepreneurial action entrepreneurial orientation and its effect on sustainability decision tradeoffs: the case of sustainable fashion firms sustainable lifestyles: addressing climate change and social inequity building theories from case study research theories building from cases: opportunities and challenges green to gold: how smart companies use environmental strategy to innovate, create value, and build competitive advantage developing sufficiency-oriented offerings for clothing users: business approaches to support consumption reduction ontologies, socio-technical transitions (to sustainability), and multi-level perspective a review on circular economy: the expected transition to a balanced interplay of environmental and economic systems telework, the timing of work, and instantaneous well-being: evidence from time use data fourth paths to business model innovation meet the repair maker: peter mui of fixit clinic the new heretics: hybrid organizations and the challenges they present to corporate sustainability path creation for sustainable consumption: promoting alternative heating systems in finland identifying, mapping, and monitoring the impact of hybrid firms massachusetts commercial food waste ban economic impact analysis prosperity without growth: economics for a finite planet degrowth in business: an oxymoron or a viable business model for sustainability? restructuring time: implications of work-hours reductions for the working class temporary reduction in daily global co emissions during the covid- forced confinement key findings from the study on lifestyle carbon footprints: long-term targets and case studies of the carbon footprints of household consumption sustainable entrepreneurship, innovation, and business models: integrative framework and propositions for future research social and sustainable entrepreneurship (advances in entrepreneurship, firm emergence and growth the emergence of a successful eco-industrial park in the united states sustainable entrepreneurial process: from idea generation to impact measurement covid- : implications for business the impact of social norms on entrepreneurial action: evidence from the environmental entrepreneurship context sustainable lifestyles : stakeholder visions, emerging practices and future research global greenhouse gas emissions will hit yet another record high this year, experts project the circular economy: an interdisciplinary exploration of the concept and application in a global context global climate change: vital signs of the planet unpacking the sustainability landscape sustainable business models, venture typologies, and entrepreneurial ecosystems: a social network perspective waste not want not: sweden to give tax breaks for repairs designing away waste: a comparative analysis of urban reuse and remanufacture initiatives the interaction between network ties and business modeling: case studies of sustainability-oriented innovations escaping the green prison: entrepreneurship and the creation of opportunities for sustainable development right to repair wraps up a big year europe, let's reuse, refurbish, repair the circular economy: barriers and opportunities for smes semi-new computers welcomes you business models for sustainability: a co-evolutionary analysis of sustainable entrepreneurship, innovation, and transformation transitions for sustainable consumption after the paris agreement. sustainability: science, practice and policy distinctions not dichotomies: exploring social, sustainable, and environmental entrepreneurship unep. . fostering and communicating sustainable lifestyles food security status of u.s climate change and waste corporate-entrepreneur collaborations to advance a circular economy entrepreneurs in sustainable consumption: the furniture trust case the need for better measurement and employee engagement to advance a circular economy: lessons from biogen zero waste journey understanding and addressing business needs and sustainability challenges: lessons from devens eco-industrial park food for free: from food waste to healthy meals sustainable consumption dilemmas environmental dystopia versus sustainable development utopia: roles of businesses, consumers, institutions, and technologies the entrepreneur-environment nexus: uncertainty, innovation and allocation highlights • entrepreneurs as civic and political actors who help create momentum for political changes • their value proposition based on time & cost savings, social & env. impact, and quality service • it, sustainability networks, and social media -key to developing viable business models • key challenges: costly sustainable actions, impact measurement, resources, brand awareness • shifting to sls requires stakeholder collaborations and bold policy action the role of entrepreneurs in advancing sustainable lifestyles: challenges, impacts, and future opportunities vesela veleva: conceptualization, methodology, data collection and analysis, writing-original draft preparation the authors would like to thank all participating companies and the university of massachusetts boston for funding this research through the umass boston public service grant, project: p . higher cost of product compared to imports from china; lack of interest from consumers; lack of resources (funding and time) to do good measurement (e.g., policies to tax raw materials (so recycled materials will be price competitive); investment in better recycling technology j o u r n a l p r e -p r o o f ☒ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐the authors declare the following financial interests/personal relationships which may be considered as potential competing interests: vesela veleva sept. , j o u r n a l p r e -p r o o f key: cord- -xfuwawlu authors: reynolds, joel michael; guidry-grimes, laura; savin, katie title: against personal ventilator reallocation date: - - journal: cambridge quarterly of healthcare ethics : cq : the international journal of healthcare ethics committees doi: . /s sha: doc_id: cord_uid: xfuwawlu the covid- (coronavirus disease of ) pandemic has led to intense conversations about ventilator allocation and reallocation during a crisis standard of care. multiple voices in the media and multiple state guidelines mention reallocation as a possibility. drawing upon a range of neuroscientific, phenomenological, ethical, and sociopolitical considerations, the authors argue that taking away someone’s personal ventilator is a direct assault on their bodily and social integrity. they conclude that personal ventilators should not be part of reallocation pools and that triage protocols should be immediately clarified to explicitly state that personal ventilators will be protected in all cases. the coronavirus disease pandemic has led to intense conversations about ventilator allocation and reallocation during a crisis standard of care (csc). the ethical value of maximizing lives saved in a pandemic has received widespread support from clinicians and bioethicists for years, so much so that some consider it a fundamental tenet of public health ethics. in the last few months, however, approaches that prioritize maximization of life have received repeated and notable challenges. one reason for such pushback is the implication that patients who could benefit from a ventilator might have the ventilator withheld or withdrawn if triage officers/teams decide that more patients could be saved by taking it from them. this reasoning could extend to ventilators outside the hospital setting; if more lives could be saved by taking advantage of chronic-use ventilators in the community, then it would follow that these ventilators should be part of allocation schemas. this is not a mere academic point. the food and drug administration issued guidance for modifying home-and facility-use ventilators as needed for the covid- pandemic. in new york, the federal government continually refused to provide needed support and the covid- pandemic overwhelmed hospitals so severely that governor cuomo authorized the national guard to take control of excess community ventilators, announcing his plan in an april briefing that caused some alarm. as another example, multiple hospitals approached a nursing home in long island, requesting access to unused ventilators; the first hospital to make the request received ventilators, leaving the facility with only on hand for current and future residents. even outside of new york, healthcare systems globally must find ways to increase supplies and plan for csc. bioethicists, healthcare professionals, and public agencies must pay attention to this concern and clarify promptly: are personal ventilators (pvs) part of the reallocation pool during a pandemic like covid- , or not? in this paper, we focus on the primary ethical question that underlies such a decision: should they be or not ? we argue that pvs should not be part of reallocation pools and that triage protocols should be immediately clarified and explicitly state that pvs will be protected in all cases. as important as we take our primary argument to be, we take the issues raised by personal ventilator reallocation (pvr) to have biomedical, ethical, and philosophical import far beyond crisis standards of care in the time of covid- . first, as we will discuss at length, there is an urgent moral need for explicit policies concerning ventilator reallocation at the institutional, state, and federal level. second, pvr raises crucial symbolic issues concerning the historically fraught relationship between the norms of biomedical and public health practices and the needs and wellbeing of the larger disability community. we begin by analyzing phenomenological, neuroscientific, ethical, and sociopolitical considerations pertaining to the experience of long-term ventilator users, the analysis of which leads us to argue that ventilators should be considered as an integrated technology: a technology that is essential to one's functioning across the life course and part of one's social identity. we then discuss the ways in which integrated technologies such as ventilators have become powerful symbols concerning the worth of disabled lives amidst this political and existential crisis. heeding the fact that multiple values are at play when csc are triggered, in the next section, we analyze four potential scenarios of pvr during a pandemic as well as the ethical considerations of each. in conclusion, we discuss the larger implications of our argument that reallocating pvs under any circumstances grossly violates bodily and social integrity and conflicts with longstanding biomedical principles and guidelines. for the purposes of our discussion, the acronym "pv" refers to ventilators that individuals use in their homes, whether that be private homes in a community or in long-term care environments, such as group homes and nursing homes. a person's financial relationship to these ventilators may differ-for example, one might rent, borrow, or own their ventilators, and this relationship is likely mediated by health insurance. some bioethicists suggest that whether a ventilator is "rented from a device company" and whether there is "legal ownership" are ethically salient for claims to the ventilator during a pandemic. for reasons we defend below, we take the nature of the financial relationship to be immaterial to the personal sense of ownership that a ventilator user experiences and the ethical considerations thereof. the possibility of pvr through a triage process is a source of profound concern for people who rely on ventilators in their everyday life. alice wong, a disability activist and a long-term vent user, explains this concern: "were i to contract coronavirus, i imagine a doctor might read my chart, look at me, and think i'm a waste of their efforts and precious resources that never should have been in shortage to begin with. he might even take my ventilator for other patients who have a better shot at survival than me." although states and individual institutions vary in their pvr policies, discussion of pvr has been covered in the media and implanted as a concern in disability communities. the introduction of this possibility-that one could go to the hospital to receive acute care services and end up without access to the life-sustaining device that they have constant access to at home-is a valid joel michael reynolds et al. deterrent to going to the hospital when otherwise necessary. moreover, silence on an issue during a public health crisis can be decisive; the nature of a crisis is such that, without clear guardrails, options that are ethically problematic can remain on the table in policy discussions and then lead to action. as a result, we contend that there can no longer be neutral, or assumed, defaults in ventilator triage policies. our analysis is part of a debate that has existed for over a decade about how chronic-use ventilators should factor into triage decisions during a public health disaster. the guidance for establishing crisis standards of care for use in disaster situations by the institute of medicine (now national academy of medicine) describes early stages of this debate. according to this report, the world health organization at the time argued that "chronic-care patients should be included with all other patients in triage protocols, holding that all must share the sacrifice involved in triage equally," whereas the veterans health administration "found that viable ethical arguments could support either position," although they ultimately chose to exclude pvs from reallocation. recently in the new york times, ari ne'eman claimed that the new york triage guidelines would "permit hospitals to take away ventilators from those who use them on an ongoing basis in the community or at a long-term care facility if they seek hospital care." joseph fins, who served on the task force responsible for these guidelines, refuted this characterization of the task force's recommended ventilator reallocation process. the exchange between ne'eman and fins underscores the importance of clarity and transparency. in the past few months, complaints of disability discrimination in triage protocols in kansas and new york were submitted to the u.s. department of health and human services office of civil rights, explicitly asking for protection of pvs from reallocation. months into the covid- pandemic, the new england journal of medicine published a perspective piece that advises against pvr in light of disability discrimination complaints, although the ethical reasons for this recommendation are ultimately left unaddressed-the comment is instead a single sentence assertion. other bioethicists have left it an open question to what extent pvr should be permitted, raising some doubts about "legitimate" claims and expectations of pv users. what is the lived experience of a pv? one of the more established values of medical practice is respect for patient autonomy, including respect for patients' bodily integrity. although there are many gray areas in medicine, it is typically taken as a given that infringing on a patient's bodily integrity should only occur under exceptional circumstances. yet, what if a patient's body extends beyond the skin? is a guide dog part of a patient's body? what about an implanted cardioverter-defibrillator or a cochlear implant? this is the dilemma faced by people who live with ventilators: will medical professionals view their ventilator as a part of their body and something to be carefully respected or as a mere object they use that can be taken away? it is hard to overstate the personal terror wrought from the suggestion that pvs could be taken away in a triage process, but to fully appreciate why this causes such terror requires better understanding the lived experience of longterm ventilator users. if medical providers, health policy experts, and others who play a role in decision-making concerning pvr wish to make informed and ethically defensible decisions, then attention to how long-term ventilator users experience their ventilator must be heeded. recent neuroscientific studies suggest that the multisensory mechanisms representing peripersonal space do not depend merely upon bodily activity or upon active use of nonbodily items such as tools. on the contrary, peripersonal space is a question of the processing of information resulting from organism-environment interactions. for example, galli et al., who focus on the use of a wheelchair, argue that a wheelchair "can be conceived as a whole body tool, enabling extended interaction between the person and the environment, thus extending peripersonal space boundaries." however, they note that "counter-intuitively, such effect was not induced by active use of the wheelchair in healthy participants who never used a wheelchair before (even if they subjectively reported to "embody" the wheelchair)" (idem). tellingly, to merely use an object for some discrete period of time is not sufficient for it to become a part of the proprioceptive sensing of an organism. that is to say, there is a crucial distinction between using an artifact, becoming habituated to using an artifact, and having become habituated to using it to the point of incorporating it into one's experience of one's body itself. seen in this light, longterm ventilator use is not ultimately a question of becoming habituated to the use of a ventilator, but instead of bodily incorporation of the ventilator. still, this argument alone does not decide the matter of pvr. we are not primarily concerned with whether a person senses or perceives their ventilator as a part of their body, but, instead, whether or not such a sensation can act as the foundation of a moral claim that removing their ventilator is a harm, including a harm that infringes on their bodily integrity. that is to say, as insightful as phenomenological and biological insights are, they do not, on their own, answer the ethical problem at hand. to answer that question requires a different analytic toolset. consider the widely used distinction between curative and assistive technologies. curative technologies are typically taken to be technological artifacts that contribute to a person's shift toward comparatively "normal" or "healthy" forms of being, whereas assistive technologies are typically taken to be merely additive and helpful with respect to how one is. in "the distinction between curative and assistive technology," joseph stramondo argues that this distinction is untenable if thought in terms of an extensional or intentional definition. the reason for this is that the meaning of the technologies in question does not turn on what the respective concepts are taken to pick out, but instead upon the relationship that a given technology has to one's "relational narrative identity as a member of one of two social groups: disabled people or nondisabled people." stramondo's claims situate social and dialogical factors relative to politicized identities as definitive-as opposed to biological, phenomenological, and psychological factors. this is an insightful argument in many respects, but we wonder whether it appropriately extends to the case at hand. does the permanent use of a ventilator turn, when all is said and done, solely on the story one tells about oneself and/or which others tell about one? it seems as though the distinction between therapeutic and assistive technology as tethered to relational narrative identity is insufficient to fully capture the normative dimensions of the use of a technology like a long-term ventilator. we suggest that the meaning of a ventilator for a long-term ventilator user should instead be construed neither in terms of a therapeutic, nor assistive technology, but instead in terms of what we call an integrated technology. more specifically, it is a corporeally integrated technology. although the meaning of a ventilator for a long-term joel michael reynolds et al. user is certainly determined by their relational narrative identity, as stramondo's work rightly suggests, the moral stakes of the relationship between the user and the ventilator is not reducible to that. this is because without this technology, the person would die or would be thrown into a medically dangerous situation. this is part of the reason that ventilators should be treated as prima facie morally distinct from other sorts of similar technologies. let us unpack this argument further. in his essay, "prosthetic embodiment," sean aas argues that dominant accounts of the moral status of prosthetic or other sorts of bodily extensions fail to motivate expected normative concerns-they do not tell us why we should care about damaging or taking away someone's prosthetic leg, for example, in the ways that most would expect. after analyzing why phenomenological, neuroscientific, and biological accounts, such as we are analyzing here, fail to provide such ethical considerations-why they do not tell us how we should distinguish between morally meaningful bodily and nonbodily parts-aas articulates a solution: "to be a body part is to be the sort of thing that ought to be protected, in a certain way, by social practices." the question then immediately arises: which practices support which sort of social practices in question? "following arguments from anita silvers and other philosophers of disability," aas continues, "the thing that social institutions ought to protect, in this bodily way, are those things that are critical to our functioning as equals in our actual social world" (idem). but the philosophical weight is then left on the adjective "critical." and, furthermore, aas' response does not substantively address questions of how we adjudicate debates over what is critical and noncritical. this is understandable for such debates are storied and difficult. consider the following phenomena: personal computer use, equal representation within a democratic republic, the ability to metabolize the amino acid phenylalanine, access to basic healthcare services, prostheses for lower-limb amputees, and eyeglasses. to determine which of these "are critical to our functioning as equals in our actual social world" and which are not goes to the heart of debates over justice and equity and which-assuming one is operating under real, nonideal conditions-are very hard to answer. we think, however, that aas in fact offers a path forward later on in the paper. in a footnote addressing carter and palermos' work on the ethics of extended cognition, he distinguishes between "acts that ought to count as offenses against the person because they are interference with items that realize cognition" versus those items that "interfere in cognition." switching from the issue of cognition to pulmonary functioning, a ventilator, for a long-term user, is not something which merely interferes (positively) in pulmonary function, but which realizes livable pulmonary function for them. to bring together both stramondo's and aas's analyses, then, we can say that what it means to call a ventilator an integrated technology is as follows: integrated technologies are essential to one's functioning, not merely in acute situations, but across one's future life course, and they are part of one's relational narrative identity. someone might object that there could be a long-term ventilator user who resents using their ventilator, who feels alienated from this equipment. instead of being part of the story they tell about themselves, it is a facet of their life they downplay, ignore, or otherwise diminish. yet, even in such a case, it is a part of their relational narrative identity-they have to tell a story about it. refusing to tell that story or to incorporate various aspects of it does not mean that the story or the parts in question are not against personal ventilator reallocation constitutive, on at least some integral level, of one's larger identity-again, even if through refusal or active denial. the ventilator shapes daily interactions and the conditions for living, making a narrative relationship with it mandatory. another reason why a ventilator has to be part of one's relational narrative identity, even if through the mode of refusal, is that it is not simply functionally essential, but it is so in a socially obtrusive way. ventilators, based on current technologies, cannot be hidden; on the contrary, ventilators are the sort of thing that one has to explain or that are simply taken as an aspect of another's relational identity, even if that persons wishes them not to be so, as discussed above. it is for all these reasons that a ventilator for a long-term user is in many respects categorically different from other sorts of medical technology. given these neuroscientific, phenomenological, ethical, and interpersonal reasons, taking a ventilator away from a long-term user is more akin to taking away a part of their body and a part of their identity. that is to say, it is more akin to violating both bodily and what we term "social integrity" than it is to taking away a device that someone merely "uses." still, someone might object that this account does not hold for someone who recently started using a long-term ventilator. this objection assumes that the meaning of the ventilator for that person begins at the moment they start using it, but this assumption is misguided. a person who ends up using a long-term ventilator is unlikely to have that option presented to them out of the blue. on the contrary, they were likely on a complicated medical trajectory that led up to their use of such a device. being discharged with a long-term ventilator is part of a process that most people would have been on for quite some time. although the harm against someone who has been using a long-term ventilator for a few hours or days would certainly be different in degree than someone who has been using one for or years, we contend that it would not ultimately be different in kindspecifically given the way in which long-term ventilator use constitutes an integrated technology as we have defined that term. to summarize, what commits us to grant moral status to objects such as ventilators for long-term users, artifacts that are admittedly not prima facie part of one's "biological" body, is whether or not they are integrated in the sense of both participating in and realizing the essential functions of their biological life and the narrative relational identity of their social life. following aas, we leave the ultimate meaning of "essential" (or, as he terms it, "critical") undefined in any technical sense and following stramondo, we leave the ultimate meaning of "identity" similarly undefined in any technical sense, but we do so because we think that further specifications of those terms do not undermine our central argument. to put things in an overly simplistic manner, it is neither up for debate that the ability to breathe is essential for human organisms, nor that extrinsic, socially conspicuous devices affording such essential abilities will become a part of the story one and others tells about oneself. the research we have engaged and the arguments we have put forward lead us to the following conclusion: taking away someone's ventilator is a direct assault on their bodily and social integrity. it is morally akin to taking away a part of their physical body and a part of their social identity. respect for patient autonomy as well as bodily and social integrity demands that pvs not be taken from those who use them. even replacements of ventilator devices-due to conditions where shifting to a different type of ventilator device is medically indicated-should be done in careful consultation with patients. as far as these arguments take us, they do not address an equally important consideration: the public, symbolic importance of debates over and decisions concerning pvr. it is one thing to claim that pvr is wrong from a biomedical or philosophical lens; it is another to appreciate the harms that even suggestions of pvr can cause at the larger level of public discourse and the public imaginary, especially in light of centuries of disregard, disparagement, and far worse forms of treatment of numerous communities of people with disabilities both in the united states and abroad. in this light, it is no surprise that ventilators have become a focal point of resource triage debates and advocacy in many disability communities and have in many ways taken on symbolic meaning amounting to the perception of one's social worth -whether people are "worth saving" and whether they live "lives worth living," to invoke the language of the third reich's t program. as horror stories emerged from italy about ventilator shortages and the painful act of deciding who would or would not receive a ventilator were recounted, the prospect of triaging ventilators was highly anticipated in the united states. the pandemic has underscored and compounded long-standing health inequities in the united states, especially in black and latinx communities, including lack of access to testing and health information; lack of access to routine, primary care, and increased exposure to the virus due to lack of personal protective equipment (ppe) and disproportionate numbers of frontline, "essential" workers. still, public discourse and broadly publicized communication among elected officials have continued to highlight not the role of systemic inequality and measures to address it, but instead concerns about supply-side issues such as ppe and ventilator access. the outsized presence of ventilators in the media magnifies their symbolism as the machine that gives access to life when all else is lost. new york governor andrew cuomo declared in mid-march, , "ventilators are to this war what missiles were to world war ii," adding a touch of patriotism to the state's efforts to procure ventilators. the covid- pandemic is not the first time that breathing has taken on greater meaning than its mechanical function. in the case of the brutal murder of unarmed black man eric garner in new york city in , police put mr. garner in a choke hold that suffocated him. videos of the attack recorded his final words, "i cannot breathe," a phrase which he repeated times as he was choked to death. later, when swells of outraged people filled the streets protesting the senseless killing, these three words were repeated as rallying cries, on signs, and as a protest hashtag on social media. again in , when minneapolis police suffocated another unarmed black man, george floyd, the scene was recorded by video and his last words reverberated across the nation: "i cannot breathe." the words became a rallying cry again, representing the systematic denial of breath and therefore life. air, lungs, breathing and, now, ventilators have long been symbols for essential life and hope. once used as a means of determining death, the ability to breathe is a fundamental part of human life. although biomedical advancement from the iron lung to the ventilator has provided alternative mechanisms for exchanging oxygen and carbon dioxide, one's capacity to breathe is so fundamental to life it remains one indicator for brain death. in sontag's discussion of the metaphors associated with tuberculosis, she suggests a "disease of the lung" is a "disease of the soul," so that even in its metaphoric form, the organ responsible for breathing is allencompassing. thus, any discussion of ventilators is inevitably going to provoke strong reactions. as this pandemic has exposed deep societal inequities, discussions of triage protocol related to social identities, such as that of disability, may seem like a referendum on the worth of the lives of these groups. discourse throughout this pandemic has continually rendered disabled communities as other, and also often as lesser, than the nondisabled, working-age adult. at the start of the pandemic, news reports repeatedly assured listeners that "only older people and people with underlying conditions" have suffered critical illness and deaths from covid- . in response, many disabled activists wrote critiques with sarcastic comments such as, "do they not know we can read?" similarly, the discussions about pvr struck fear into long-term ventilator users and their loved ones that rippled across disability communities. the fact that pvs were ever a point of contention is not likely to be forgotten, especially if triage protocols never explicitly state that pvs are protected from reallocation. in order to work toward establishing trust in healthcare systems-which is an important component of health equity in the present and for the future-the collective trauma of the covid- pandemic needs to be a part of our decisionmaking both today and going forward. for disability communities, this may mean understanding the fears that may arise around accessing basic care and making explicit policies that rebuke particularly charged ideas, such as pvr. public health officials, bioethicists, and healthcare providers must contend with the realities of the ventilator as a symbol of life and worth, while not over-focusing on ventilators in a pandemic response to the detriment of increasing access to more basic primary care and ppe. the task for public health messaging is to reframe the meaning of a ventilator as a tool that may help in limited, specific, situations, yet is not in and of itself indicative of quality of care. there are many challenges facing disabled people during this pandemic, and there will be many challenges when the world starts to recover. now that we have detailed a number of arguments and considerations objecting to the reallocation of pvs, we will turn to address specific scenarios in which the demand for reallocation may arise and explore in far more detail how, in our view, clinicians and providers should respond. to better understand how csc might lead to a pv user not having access to a ventilator during a pandemic like covid- , and to make our analysis and recommendations more concrete, we lay out the following four scenarios. ventilators intended for chronic use outside of the hospital setting could be acquisitioned by hospital systems that are desperate. local authorities could ask chronic-care facilities to hand over ventilators to shore up dire shortages. this acquisition could focus on excess ventilators, that is, those not in use. alternatively, all of the ventilators in these facilities could be considered part of the allocation/ reallocation pool, even subjecting residents of chronic-care facilities to a triage process. joel michael reynolds et al. whether retrieving excess ventilators from facilities is ethically permissible would depend on whether this would place undue burden on care facilities that will likely need those ventilators. without them, facilities may be less able to take new residents (which causes a discharge problem for hospitals), and they may not be able to replace faulty ventilators (creating a precarious threat to current ventilator users in the facility). a reciprocity agreement between the requesting hospital(s) and the facility could help mitigate these concerns. government agencies should explicitly give chronic care facilities the freedom to opt out of these arrangements, which means giving some protection against negative repercussions to facilities' funding and public relations if they refuse. if a facility does decide to share their excess ventilators, there should be continual communication and evaluation of the facility's needs, and there should be clear triggers for returning ventilators back to the facility to prevent time lags that lead to devastating consequences for vulnerable facility residents. making all chronic-use ventilators part of the reallocation pool has been longconsidered ethically impermissible for several reasons. the iom/nam report points out that it would require an unacceptable role reversal for facility caregivers and would cause brutal and unjust harm to persons with disabilities. the new york state task force and life and law report argues: "to triage patients in chronic-care facilities once the guidelines are implemented may theoretically maximize resources and result in more lives saved, but conflicts with the societal norm of defending vulnerable individuals and communities." they add, "this approach fails to follow the ethical principle of duty to care and could be construed as taking advantage of a very vulnerable population." the covid- pandemic has seen this debate resurface, but we agree with the new york task force that pv users in facilities should not be subjected to reallocation for the reasons they suggest, further bolstered by our concerns for bodily and social integrity. one could counter that pvr in this scenario can be ethically acceptable-perhaps even obligatory-when the resident is in a prolonged vegetative state; this disorder of consciousness might seem to preclude the possibility of the patient ever having a sense of personal ownership over the ventilator. in a public health crisis, therefore, it might seem sensible to reallocate ventilators for this particular population, so more patients in acute need can be saved in the pandemic. we now know, although, that vegetative states are commonly misdiagnosed, and recovery can be possible; permanent vegetative states are no longer even accepted as a nosological category. furthermore, the issue of the protection and medical care of people in such states, however, medically defined, goes to the heart of disability rights. safeguarding the rights to care and recovery of this vulnerable population is therefore still a fundamental obligation of healthcare professionals and caregiving facilities, and our concerns about bodily and social integrity remain. whenever a patient comes into the hospital with their pv, the patient might no longer be allowed to "lay claim" to that ventilator. the ventilator becomes part of the allocation pool for the public good, and the patient might not have their ventilator returned to them. objections to any such policy are justified. this would be akin to seizing someone's vital organ for public use, for all the reasons we have detailed. this leaves people who are dependent on their ventilator little choice but to avoid the against personal ventilator reallocation hospital at all costs, especially if the triage criteria mean that they might not receive ventilator support during their hospitalization. furthermore, this scenario would likely cause enormous moral distress for clinicians. to our knowledge, no hospital is considering commandeering pvs, even under csc. given the immense fear surrounding this possibility, hospitals should immediately allay these concerns through policies that explicitly eliminate this possibility. someone who relies on a pv for chronic care could be admitted to the hospital. hospital-based healthcare workers are generally not trained to use home ventilator equipment, so they may want to switch out the pv for a hospital ventilator. the hospital's ventilator may be functionally equivalent to the home ventilator and the patient's respiratory support adequately provided by either the pv or the hospital ventilator. the patient should be consulted about their preferences regarding switching out ventilators in this scenario, given pervasive fears about pv confiscation under csc. especially if the type of ventilator in question is scarce, the default should be to work with the patient's own ventilator. this would be a departure of standard practice, since usually patients do not use their own equipment when they enter the hospital setting, even if they are functionally comparable. if the hospital cannot accommodate continued use of the pv for that particular patient, the pv should be placed in protected storage; even if the pv could be cleaned and repurposed for other patients, the pv should be treated like other personal items and not used without the patient's explicit consent. a ventilator-sharing system could be ethically supportable if a pv user cannot continue to use their ventilator and another patient would benefit in conditions of scarcity, but this system needs numerous safeguards to ensure that sharing is voluntary and that the pv does not remain in use so long that the pv user has delayed discharge as a result. if a patient's needs are best served by having their own caregiver at the hospital, this should be accommodated to the extent possible. a pv user could be admitted to the hospital and develop acute respiratory distress syndrome (ards) from covid- or another condition. in this scenario, the medical team would recommend switching to a ventilator capable of providing increased support; namely, switching from a basic ventilator to a full-featured ventilator-with covid- , oxygenation or high-precise fio is a central concern. such a patient would be subject to the same triage process as anyone else for the fullfeatured ventilator, so they may or may not receive the needed ventilator in the end. how likely this scenario is will depend on ( ) whether the pv really cannot provide the needed support and ( ) how close the hospital is to csc. long-term ventilator users often have specialized expertise in how to adjust their ventilators for changing needs, so healthcare professionals should partner with these patients and share their own expertise as much as possible early in admission. if the triage criteria are such that the patient might not receive the full-featured ventilator, this may or may not be equitable allocation depending on the criteria and one's conception of equity, which is unfortunately outside the scope of this paper. as physicians and scientists have more time and data points to understand the trajectory of the novel coronavirus, they may determine that they can provide more and better care without relying so heavily on ventilators. although less-invasive methods such as bipap (bilevel positive airway pressure) and cpap (continuous positive airway pressure) may aerosolize secretions and pose risk to healthcare workers and other patients, high-flow nasal cannula could be as effective as intubation and mechanical ventilation yet without the many harmful side effects from long-term intubation. as relevant as those facts are, the import of our analysis holds even if it is determined that ventilator use is ineffective for the coivd- pandemic. our arguments that the practice of pvr should be denied in all cases do not turn on the effectiveness of ventilators in csc, but upon the ethical considerations of the experience of pv use. furthermore, we have not provided an argument deduced from principles-whether nonmaleficence, beneficence, efficiency, efficacy, the public good, or what have you-but instead, an argument from the moral claims that arise from how people experience their lives. we take the further implications of our arguments to extend to at least the following two claims. first, insofar as healthcare systems aim to both form a productive partnership with disability communities and also aim to deliver just and equitable care for patient populations at large, decision-making and deliberation concerning both policies and day-to-day clinical dilemmas should involve disability perspectives. ideally, this should come from people inside of disability communities and, where that is impossible, disability allies and advocates. the integration of the perspective, experiences, and reflections of people with disabilities will only improve the ideal of just and equitable delivery of healthcare. second, the moral distinction for which we have argued here, based as it is upon the lived experience of pv users, displays the broader analytic and clinical import of analysis grounded in first-person as opposed to merely third-person analysis. third-person analyses arising from domains ranging from clinical biomedical research to quantitative sociology are profoundly valuable. we find, however, that they are significantly bolstered, especially with respect to ethical considerations, when supported and/or amended by first-person perspectives arising from phenomenological and other forms of qualitative analysis. furthermore, we contend that certain biomedical dilemmas, specifically with respect to their normative dimensions, will be poorly addressed except insofar as they are ultimately grounded in the latter and not the former. it is in light of these considerations that we argue that taking away someone's pv is a direct assault on their bodily and social integrity, that pvs should not be part of reallocation pools, and that triage protocols should be immediately clarified and explicitly state that pvs will be protected in all cases. ethics of reallocating ventilators in the covid- icu triage: how many lives or whose lives disability, likelihood of survival, and inefficiency amidst pandemic opinion | the way we ration ventilators is biased. the new york times the toughest triage-allocating ventilators in a pandemic, nejm enforcement policy for ventilators and accessories and other respiratory devices during the coronavirus disease (covid- ) public health emergency guidance for industry and food and drug administration staff cuomo clarifies plan to seize ventilators, expects to get statewide cuomo plans to use national guard to seize ventilators from upstate facilities nursing homes have thousands of ventilators that hospitals desperately need. kaiser health news (blog) disability rights as a necessary framework for crisis standards of care and the future of health care setting priorities fairly in response to covid- : identifying overlapping consensus and reasonable disagreement does the coronavirus pandemic make someone who is disabled like me expendable? vox respecting disability rights-toward improved crisis standards of care institute of medicine (us) committee on guidance for establishing standards of care for use in disaster situations opinion | 'i will not apologize for my needs new york state task force on life and the law ventilator allocation guidelines: how our views on disability evolved the wheelchair as a full-body tool extending the peripersonal space such a contention finds support in the growing research on embodied-and not just embeddedcognition body-extension versus body-incorporation: is there a need for a body-model? the distinction between curative and assistive technology havi carel's work on breathlessness further demonstrates that technologies concerning the lungs and respiratory system should not be treated similarly as, for example, a lower leg prosthesis or eyeglasses carel h. breathlessness: the rift between objective measurement and subjective experience wellcome trust-funded monographs and book chapters prosthetic embodiment. synthese it cannot "dys-appear" in drew leder's sense of the term. leder d. the absent body disability and the justification of inequality in american history american eugenics: race, queer anatomy, and the science of nationalism deadly medicine: project t , mental disability, and racism opinion | facing the fact of my death. the new york times the macgyvers taking on the ventilator shortage. the new yorker eric garner video: staten island police chokehold death. time modern death: how medicine changed the end of life the toughest triage-allocating ventilators in a pandemic. nejm illness as metaphor and aids and its metaphors the cripples will save you': coronavirus message from a disability activist ventilator allocation guidelines: new york state task force on life and the law new york state department of health see note rights come to mind do new york state's ventilator allocation guidelines place chronic ventilator users at risk? clarification needed human biodiversity conservation: a consensual ethical principle acknowledgments: we extend our thanks to the many activists and scholars who have hosted webinars and other events to share the insights and experiences of the disability community during the covid- pandemic. key: cord- - zvi k l authors: wong, sandy; mclafferty, sara l.; planey, arrianna m.; preston, valerie a. title: disability, wages, and commuting in new york date: - - journal: j transp geogr doi: . /j.jtrangeo. . sha: doc_id: cord_uid: zvi k l in the u.s., substantial employment and wage gaps persist between workers with and without disabilities. a lack of accessible transportation is often cited as a barrier to employment in higher wage jobs for people with disabilities, but little is known about the intraurban commuting patterns of employed people with disabilities in relation to their wage earnings. our study compares wages and commute times between workers with and without disabilities in the new york metropolitan region and identifies the intraurban zones where residents experience higher inequities in wage earnings and commute times. we obtained our data from the public use microdata sample (pums) of the american community survey (acs) for the – time period. we used linear mixed-effects models and generated separate models with log hourly wage or one-way commute time as the dependent variable. we find significant differences in wages and commute times between workers with and without disabilities at the scale of the metropolitan region as well as by intraurban zone. at the metropolitan scale, disabled workers earn . % less and commute one minute longer on average than non-disabled workers. high commute and wage inequalities converge in the center, where workers with disabilities are more likely to use public transit, earn . % less, and travel nearly four minutes longer on average than workers without disabilities. these results suggest that transport options are less accessible and slower for disabled workers than they are for non-disabled workers. our findings indicate a need for more accessible and quicker forms of transportation in the center along with an increased availability of centrally located and affordable housing to reduce the disability gap in wages and commute times. we also find that workers with disabilities generally seek higher wages in exchange for longer commute times, but the results differ by race/ethnicity and gender. compared to white men, minority workers earn much less, and white and hispanic women have significantly shorter commute times. our findings offer new geographic insights on how having a disability can influence wage earnings and commute times for workers in different intraurban zones in the new york metropolitan region. people with disabilities have historically had restricted access to the labor market and their adverse economic circumstances -borne of discrimination on the basis of disability status and subsequent inequities in wages -are a global problem (mitra et al., .; schur, ; lindsay and houston, ) . in the u.s., among working-age people, inequities in workforce participation or employment persist along the axis of disability status (schur, ; sevak et al., ) . in , only % of individuals with disabilities in the labor force (i.e., currently working or actively looking for work) were employed -a access, individual competencies, health-related constraints, employer attitudes regarding disability, job opportunities and requirements, the availability of workplace accommodations and other employment resources, and the structure of the public disability benefit system crudden et al., ; gewurtz et al., ; vornholt et al., ) . these factors are perpetuated by ableism (i.e., the structural and societal devaluation of and discrimination against disabled people) and have led to low employment rates and negative financial outcomes for people with disabilities (england, ; gleeson, ; sarrett, ) . more importantly, employment alone is not an economic panacea for people with disabilities because they are often sorted into 'low' and 'medium' skill occupations, which are more vulnerable to job losses during economic downturns (kaye, ) . they are consequently paid much lower wages than people without disabilities, which brings about and reinforces pay inequities. compared to non-disabled workers, disabled workers earn to % less on average in the u.s. gunderson and lee, ; schur, ) . the pay gap remains significant across age groups and levels of education for both women and men (kruse et al., ) . the reasons for these wage inequities include the changing composition of jobs over time and employer discrimination. people with disabilities experienced a decline in full-time employment from % in to less than % in . workers with disabilities are also less likely to be employed in higher paying occupations -they have been generally overrepresented in service and blue-collar jobs while underrepresented in managerial and professional positions (kruse et al., ; maroto and pettinicchio, ) . although the americans with disabilities act (ada) prohibits discrimination against people with disabilities and was expected at the outset to lead to improved access and community participation, disabled people continue to confront workforce participation barriers and inaccessible built environments impeding their mobility (bezyak et al., ; maroto and pettinicchio, ) . twenty-five years after the passage of the ada, the employment rate for people with disabilities steadily declined over time while the employment rate for non-disabled individuals remained relatively stable (maroto and pettinicchio, ) . the persistence of disparities in workforce participation after the ada, despite gains in educational attainment among disabled people, points to the limitations of lawsuits as a primary means of enforcing antidiscrimination legislation (maroto and pettinicchio, ) . furthermore, post-ada improvements to the accessibility of built environments have been too gradual. in the u.s., many communities still do not have ada transition plans for pedestrian infrastructure (eisenberg et al., ) and many public transit systems continue to be widely inaccessible, thus constraining the mobility of people with disabilities, their employment prospects, and their participation in their communities (bezyak et al., ) . a lack of accessible transportation is often cited as a barrier to employment for people with disabilities (bezyak et al., ; lubin and feeley, ) , but much less is known about the travel patterns of disabled individuals when they are employed and how their commutes relate to the localities where they live and work. in the general population, there is strong evidence to demonstrate that transportation and commuting patterns greatly influence people's job access and wage earnings (preston and mclafferty, ; kim et al., ) , but these studies do not address disability. the few studies that investigate the commute patterns of people with disabilities include deka and lubin ( ) and brucker and rollins ( ) , who found commute times to be similar between workers with and without disabilities in new jersey and across the u.s., respectively. another study by farber and páez ( ) examined adults with disabilities alone and they found public transit users to have longer commute distances to work compared to car users across canada. while these studies controlled for multiple sociodemographic factors affecting commute times, none accounted for intraurban geographies, thus overlooking how local geographic contexts influence commute times. brucker and rollins ( ) included a dummy variable for metropolitan status while the other two studies did not consider geography in their statistical models farber and páez, ) . geographic contexts, especially residential contexts, differ in the numbers, types, and locations of job opportunities; the availability of social and employment services; and transportation access and cost -all of which shape workers' commuting decisions and wage earnings. research on the entire working population shows disparities in commute time, distance, and mode across residential contexts (preston and mclafferty, ; hu, ; lee et al., ; sultana and weber, ) , and it is likely that similar disparities exist for disabled workers. more empirical work on the spatial heterogeneity of wage earnings and commute patterns would enhance our current understandings of how geographic conditions influence the socioeconomic inequities experienced by workers with disabilities. disabled workers regularly experience indignities in the form of lower wages and inaccessible built environments. if they have longer or more challenging commutes to work, this represents an additional tax on a group that has already been systematically excluded from gainful employment, and it is therefore important to identify where exactly these injustices occur to better address them. a greater attention to locational differences would generate useful information for local policy and planning initiatives, including the identification of specific neighborhoods that most need improvements to transportation infrastructure, housing development plans, and workplace discrimination. regarding mode of transportation to work, public transit use is low among u.s. workers; and for those who rely on public transportation, commutes are more taxing. in the u.s., disabled and non-disabled workers have comparably low rates of public transit use: . % and . %, respectively (brucker and rollins ) . among people with disabilities, employed individuals use public transit less than nonworkers (loprest and maag, ) . for disabled individuals, reasons to avoid public transportation include physical inaccessibility and long commute times (wong, b) . since public transit users have considerably longer work commutes than car users (farber and páez, ) , public transit use is an important covariate to control for in statistical analyses of commute times. associations between sociodemographic factors and commute time and distance have been widely studied. gender and race have important links to commuting, with white women often working closer to home than their male counterparts (hanson and pratt, ) . women's higher burden of domestic responsibilities and lower wages account in part for these gender disparities (preston and mclafferty, ; craig and van tienoven, ) . however, similar gender disparities have not been found for black, latinx, and asian workers (mclafferty and preston, ; crane, ; johnston-anumonwo, ; mauch and taylor, ) . research shows that people who work in low-wage positions often work close to home (kim et al., ) , although recent evidence suggests that in cities undergoing rapid gentrification, low-wage workers, especially minority workers, increasingly endure long commuting trips (mclafferty and preston, ) . we anticipate that these sociodemographic characteristics will intersect in complex ways with intraurban location to shape wages and commute trips for people with disabilities. our study has three main research questions: ( ) how do wages and commute times differ between workers with and without disabilities in the new york metropolitan region, ( ) how do these disparities vary between urban and suburban areas of the metropolitan region, and ( ) how are wages and commute times influenced by sociodemographic and geographic factors for workers with disabilities alone? this research provides new empirical insights into the conditions of employment and commuting for urban and suburban residents with disabilities in a major u.s. metropolitan region. we also consider how gender, race, and transportation mode, factors significant in previous research (preston and mclafferty, ; craig and van tienoven, ; deka and lubin, ; kim et al., ) , intersect with disability to influence wage and commuting trends. the study area for this research is the new york metropolitan region, an area centered around new york city. with a population of more than million, the region is the most populated in the u.s., a major economic node of integrated housing and labor markets (u.s. census bureau, ), and the largest commuting region in the u.s. jobs are concentrated in manhattan, the region's center which receives . million commuters each workday (u.s. census bureau, ). the region stands out for its extensive transit network that includes subway, bus, and light rail networks, and for its diverse residential settings that range from dense, high-rise neighborhoods in the center to low-density, exurban zones on the region's fringe. the size and geographic diversity of the region make it an important empirical case study for investigating intraurban wage and commuting trends among workers with disabilities. a focus on new york will generate insights on the wage and commuting patterns of disabled workers in the largest u.s. metropolitan region. in addition, our focus on a single metropolitan region enables us to tease out intraurban patterns that are often neglected in studies based on national data. in recent decades, the new york metropolitan region experienced distinctive changes in employment and commuting across three intraurban zones: the center (i.e., manhattan), inner ring, and suburbs ( fig. ) . from to , employment increased in the center and suburbs (moss et al., ) but decreased in the new jersey counties closest to manhattan (preston and mclafferty, ) . the relocation of jobs shaped the relationships between residential location, wage earnings, and commute time. in , workers residing in the center received the highest wages and had the shortest commutes, with commute times generally declining alongside increases in hourly wages. in contrast, workers living in the inner ring and suburbs had longer commutes in exchange for higher wages (preston and mclafferty, ) . compared to the rest of the u.s., workers in the new york metropolitan area are more likely to use public transportation to commute due to the accessibility of mass transit coupled with slow driving times (moss et al., ) . nonetheless, research showed that the customary mode of transportation to work varies by residential location and among racialized groups. in manhattan, most residents used public transit or walked to work. a higher proportion of workers in the inner ring and suburbs commuted by car. white workers were more likely to drive to work while workers of other racialized groups were more likely to utilize public transportation (preston and mclafferty, ) . to date, research on employment and commuting in the new york metropolitan region has yet to investigate how having a disability might influence these patterns. all data on employed residents in the study area were obtained from the public use microdata sample (pums) of the american community survey (acs) for the - time period. of all the national surveys conducted in the u.s., the acs collects data that is most representative of the working population. in the original dataset, each year contains a s. wong, et al. journal of transport geography ( ) % sample of the total population in the new york metropolitan region and the pooled five-year dataset represents approximately % of the study area's total population. our sample consists of all individuals who received wage or salary income in the past months. we omitted selfemployed people, people who worked at home, and individuals whose estimated hourly wage was < $ per hour. the final sample size is , workers, of which , individuals report having a disability (approximately . % of the total). we refer to the - dataset as the pums for brevity and to highlight the dataset's midway time point. individuals in pums are nested in public use microdata areas (pumas), which are the geographic areas that were statistically generated for public dissemination of pums without violating individual privacy. each puma contains at least , individuals. the study period overlaps with the macroeconomic contraction known as the great recession. during the - recession, there was widespread restructuring in both housing and labor markets, which jointly and independently affected workers, especially lower-and middle-class workers. unemployment rates in the u.s. were the highest since , with disproportionate losses borne by disabled workers, whose share of the total workforce declined by % (kaye, ) . employed individuals with and without disabilities experienced similar declines in average annual earnings over the course of the recession, but large disparities in earnings remained by disability status (maroto and pettinicchio, ) . the commuting patterns of people with disabilities during this time period have not been studied much. we know that the average one-way commute time in the u.s. dipped by a fraction of a minute during the recession (ingraham, ) and that nationally, disabled and non-disabled workers had similar commute times (brucker and rollins ; deka and lubin, ) . we use the acs's definition of disability as a binary variable (presence or absence of a 'deficit'), which is based on responses to items about limitations in hearing, vision, ambulatory, cognitive, independent living, and self-care capacity (kaye, ) . however, we recognize that the experience of disability is varied and relational. disability type and the severity of one's disability and/or health status interact with socioeconomic status and educational attainment to shape a person's perceived suitability of employment and level of compensation (schur, ) . following preston and mclafferty, , we divided the region into three zones that represent the region's diverse residential and transportation environments. the center consists of manhattan, the region's largest concentration of job opportunities and the focal point of the region's transportation networks. although the study region is polycentric, manhattan stands out as the region's single largest employment center, accounting for almost one-quarter of the region's jobs in (preston and mclafferty, ) . manhattan also represents a distinctive residential context, with its exceptionally high population and commercial densities and extensive public transit networks. the inner ring that includes brooklyn, queens, and the bronx in new york city and some adjacent areas of new jersey comprises dense residential areas that are connected to manhattan via public transit (fig. ) . the remaining areas are designated as suburbs. although heterogeneous, these areas typically have low population densities, limited public transportation, and require a long or expensive commuting trip to reach jobs in manhattan (preston and mclafferty, ) . we anticipate that the three zones may give rise to differences in wages and commute times for people with disabilities due to disparities in residential density and transit availability. compared to locations in the center and urban ring, suburban areas with lower population density have fewer public transit options and less frequent timetables, thus constraining the mobilities of disabled suburban commuters who rely on public transit (wong, a; wong, b) . in general, transportation unavailability and inaccessibility are major mobility and commuting challenges for many disabled individuals (bezyak et al., ; lubin and deka ) . unlike non-disabled individuals, disabled commuters regularly contend with physical barriers and attitudinal issues during their travels that are related to their impairment and impede their mobility (bezyak et al., ; wong, b) . for example, when using public transit, individuals with mobility or vision impairments often encounter unavailable or inoperable lifts or ramps and drivers who do not provide stop announcements (bezyak et al., ) . to investigate the pay and commute time disparities between workers with and without disabilities, our main outcome variables are log hourly wage and commute time. the pums contains total wage or salary income in the past months. we calculated hourly wage, which is equal to the wage and salary earnings divided by the estimated number of weeks worked and divided by the typical hours worked per week. we then calculated and used log hourly wage due to a positive skew in hourly wages. commute time is the one-way, selfreported time spent traveling to work on a typical day, in minutes. our two dependent variables are log hourly wage and one-way commute time to assess differences between workers with and without disabilities in terms of wages and their work commutes, respectively. we used linear mixed-effects models (lmms) with puma-level random intercepts to account for the non-independence of observations within pumas. separate lmms were constructed for three distinct dependent variables (log hourly wage and one-way commute time for the total sample, and one-way commute time for disabled individuals alone) and four different geographies (metropolitan region, center, inner ring, and suburb). independent variables in the lmms are individual characteristics that include age, education level, race/ethnicity, gender, disability, marital status, part-time work status, public assistance status, and public transit use; and puma-level attributes that include work and residential locations. in total, we generated models using the pums data. lmms are useful for representing, estimating, and accounting for the relationship between data nested at different levels, such as individuals and the groups that they belong to (subramanian et al., ) . in our case, we have individuals and the pumas that they reside in. a conventional practice is to fit a fixed effects model at one level but not the other, which can lead to individual or ecological fallacies (subramanian et al., ) . another option is to fit separate fixed effects models at the individual and group levels. an lmm is a streamlined approach because it combines these two steps into one (gelman and hill, ) . yet another alternative is to include dummy variables belonging to the group level as predictors in a fixed effects model to account for the nested data structure (mcneish and kelley, ). however, this approach is better suited when the number of groups is small (i.e., under or ) (brauer and curtin, ; mcneish and kelley, ) , whereas our sample contains groups. furthermore, fixed effects models have limiting assumptions and constraints. fixed effects models treat group-level variables as fixed variables, only explicitly modeling within-group variation and assuming to capture all the variability at the group level. fixed effects models also do not assume that groups are sampled randomly, therefore results may not be generalizable to other groups that are not included in the models. unlike fixed effects models, mixed-effects models do not have these limiting assumptions and can directly estimate group-level predictors and between-group variability without having to include an unwieldy number of parameters (brauer and curtin, ; mcneish and kelley, ) . these are the advantages for which we choose lmms over simple linear regressions. lmms extend simple linear regressions to include both fixed and random effects. in our models, the fixed effects are the constant slopes and the random effects are the varying intercepts for each puma. in other words, the intercept is allowed to vary for each puma. all pumas are assumed to have the same slope, but some may have a higher or lower intercept than the average relationship for all pumas. we calculated two types of r (marginal r and conditional r ) to quantify the variance attributable to the different types of effects. marginal r is the s. wong, et al. journal of transport geography ( ) share of the total variance explained by the fixed effects and conditional r is the proportion explained by both the fixed and random effects (nakagawa et al., ) . to quantify the wage gap between workers with and without disabilities at four discrete geographies (i.e., the entire metropolitan region and the three intraurban zones), we generated four separate lmms with log hourly wage as the dependent variable. each model represents a distinct residential area. the first model pertains to the entire study area and the other three models apply to the intraurban subregions: center, inner ring, or suburb. for these lmms, we included an interaction covariate of female and disabled to better assess the effects of gender and disability status on wages. we also calculated the exponentiated regression coefficients to present the percent increase or decrease in wages in one group relative to its reference group. to estimate the disparity in commute time between workers with and without disabilities at the scale of the metropolitan region as well as within each distinct intraurban zone, we constructed lmms with oneway commute time as the dependent variable. we generated four models, one each for the geographic zones discussed earlier. we experimented with including an interaction term for female and disabled, but it was not statistically significant and did not change the results, so we did not include it in the final models. our final research objective is to assess the impacts of socioeconomic and geographic factors on the relationship between commute time and wages for workers with disabilities alone in each of the four geographies. a focus on workers with disabilities allows us to investigate closely the economic and social influences on their commuting times at different geographic scales. separate models were created for each geographic zone with commute time as the dependent variable. we generated models at different geographic scales: at the scale of the metropolitan region and for each of the three intraurban zones. the models enable us to assess how inequalities in commuting and wages based on disability status vary among geographic context. it is possible for associations to be present in the center, but not in the inner ring or suburbs, and vice versa. by identifying where disparities in commuting and wages are highest, we can better understand the local causes driving disparities and pinpoint the localities where policy changes are critical. from the descriptive statistics alone, we find striking differences in hourly wages between workers with and without disabilities (table ) , corroborating the wage gaps reported previously in the literature (e.g., brucker and houtenville, ; gunderson and lee, ; schur, ) . we focus on median hourly wages because the mean calculations are influenced by a positive skew in the data and an outlier in the center that consists of one disabled worker earning extremely high wages. the largest wage gap is in the center, followed by the suburbs and the inner ring. in the center, workers without disabilities earn a median hourly wage of $ . while workers with disabilities earn $ . -a difference of $ . an hour. in the suburbs, the difference in median hourly wage is $ . an hour -workers without disabilities earn $ . while workers with disabilities earn $ . . the disparity in median hourly wage is lowest in the inner ring at $ . an hour, with non-disabled workers earning $ . compared with disabled workers' median hourly income of $ . . at the scale of the metropolitan region where we do not find major differences in the average one-way commute times between workers with and without disabilities, our findings are similar to those reported at national and state levels (brucker and rollins ; deka and lubin, ; farber and páez, ) . what is unusual is that we find slight intraurban differences (table ). in the suburbs, the median commute time for disabled workers is five minutes shorter than it is for nondisabled workers. consistent with national statistics indicating low levels of public transit use across the u.s. regardless of disability status (brucker and rollins ) , public transit use is not significantly different between disabled and non-disabled workers at the metropolitan scale. however, we do find small intraurban differences in public transit use (table ). in the center, a higher percentage of disabled workers rely on public transit, whereas the disparity is reversed in the inner ring. after controlling for economic, demographic, and geographic factors, we find wage disparities by disability status and gender in the new york metropolitan region, with considerable wage variation by residential location. across the metropolitan region, workers with disabilities earn % less on average than comparable workers without disabilities (table a , model ). this finding is within the bounds of existing disability wage gaps, that range from to % in previous u. s. studies schur, ) . there are intraurban variations in the wage disparity between disabled and non-disabled workers. workers residing in the center and suburbs experience the largest wage gaps followed by workers in the inner ring. compared to workers without disabilities, workers with disabilities living in the center earn on average % less in hourly wages (table a, model ) and those living in the suburbs earn % less (table b , model ). in the inner ring, the wage disparity is smallest as residents with disabilities earn % less on average than workers without disabilities (table b , model ). the wage disparity is also gendered. compared to non-disabled male workers, disabled women earn % less across the metropolitan region (table a , model ). a similar and significant wage gap also emerges in the model for the suburbs (table b , model ). disabled female workers also earn % less than non-disabled female workers in the entire metropolitan region and in the suburbs. gender disparities in wage earnings are widely recognized within the general population, with women earning less than men (preston and mclafferty, ; craig and van tienoven, ) ; however, less is known about the intersection of gender and disability. our results reveal that being female compounds the economic penalty associated with having a disability (brucker and rollins ; gunderson and lee, ) . the findings also vary by zone, indicating that female workers with disabilities who live in the suburbs face more wage discrimination than they do in other parts of the metropolitan region. intraurban inequalities in the disability pay gap are important because they reveal geographic inequities in economic mobility and financial security. in manhattan, the central zone, where wages are the highest in the metropolitan region, workers with disabilities earn much less than workers without disabilities. the large wage disparity coupled with the high cost of living in manhattan minimizes the gains for workers with disabilities in manhattan relative to those who live elsewhere in the new york metropolitan region. while residents outside manhattan have poorer geographic access to good jobs and earn lower absolute wages, they have lower housing costs (quintana, ) . the disability pay gap can have pernicious effects on the economic wellbeing of residents with disabilities. a lower wage may entail a reduced capacity to accumulate wealth and maintain financial stability. workers navigating the low wage labor market are particularly vulnerable as lower wages entrap them in a cycle of poverty (jolly, ) . across the metropolitan region, we find significant wage gaps along other social axes of difference, including race/ethnicity and gender (table a , model ). in our sample, all racialized minority workers earn much less than white workers, but the wage differences vary by group. hispanic and asian workers have the highest wage disparities at % lower wages while black workers have the lowest wage disparity with % lower wages than white workers. female workers earn % less than male workers. these results corroborate those of recent studies demonstrating that racialized minorities and women earn lower wages, thus facing greater pay discrimination in the labor market than white men (mclafferty and preston, ; brucker and rollins ). transportation mode, level of education, marital status, work status (part-time versus full-time), public assistance status, work location, and residential location also influence wage disparities (table a , model ). public transit users earn % less than workers utilizing other transportation options, mainly driving. workers with a bachelor's degree or higher level of education earn % more in hourly wages compared to those with no bachelor's degree. married workers earn % more than workers who are not married. part-time employees earn % less than full-time employees. public assistance recipients earn % less than non-recipients. approximately . % of non-disabled workers receive public assistance while . % of disabled workers receive public assistance. for all workers, the average total public assistance income in the past months was $ . manhattan workers earn % more than those who work in the inner ring and suburbs. compared to suburban residents, center residents earn . % more and inner ring residents earn % less. our findings are consistent with previous studies examining wage disparities by transport mode, level of education, and residential location (e.g., preston and mclafferty, ; brucker and rollins ; gunderson and lee, ) . the inclusion of disability as a covariate does not alter the directions of the relationships between wages and other socioeconomic and geographic characteristics. intraurban patterns generally reflect the trends at the metropolitan scale with a couple of exceptions. in the center, public transit use does not approach statistical significance (table a , model ). this is likely because public transit use is common in manhattan for workers across the wage spectrum and along other axes of social difference (preston and mclafferty, ) . the share of the total variance explained by the random effects (i.e., the varying puma-level intercepts), differs markedly between the metropolitan region, center, and suburbs. at the scale of the metropolitan region, the proportion is . %. in contrast, the proportion is highest in the center ( . %) and lowest in the suburbs ( . %). these findings indicate the importance of distinguishing central transit hubs from other intraurban zones and accounting for different levels in nested data. across the new york metropolitan region, after controlling for transit use, age, and other factors influencing commute time, there is a significant difference between workers with and without disabilities even though the coefficient estimates are notably small. the commute time for workers with disabilities is nearly one minute longer than that for similar workers without disabilities (table a , model ). our small coefficient estimates align with prior studies that found differences that were small or not statistically significant in the commuting patterns of disabled workers compared to non-disabled workers or by disability type at the state and national scales. deka and lubin ( ) compared commute time disparities between new jersey residents with and without disabilities and found small differences, and brucker and rollins ( ) found differences that did not reach statistical significance for a representative sample of the entire u.s. population. in canada, farber and páez ( ) found that disability type did not have a sizeable influence on commute distance. although differences in commute time for the whole study area are small, we find notable variation among intraurban zones after economic and demographic variables are controlled for. compared to commuters with no disabilities, commuters with disabilities living in the center travel nearly four minutes longer (table a , model ) and those living in the inner ring travel . min longer (table b , model ), which represent nearly % and % of the median commute time, respectively. in contrast, commute time differences do not reach statistical significance in the suburbs (table b , model ), which suggests that having a disability does not have a considerable influence on travel times for suburban residents. these findings extend those of extant research on national and state-level trends (e.g., brucker and rollins ; deka and lubin, ; farber and páez, ) by demonstrating geographic heterogeneity in commuting disparities within a large metropolitan region based on disability status. we find that commute times for disabled workers are longest on average in the center relative to the rest of the region, a finding that would have been masked had our analysis only took place at the scale of the metropolitan region. at the metropolitan scale, white, hispanic, and asian women have shorter commute times than comparable white men, while black women have a longer commute time (table a , model ). black, hispanic, and asian men also have longer commute times compared to white men. our findings on gender differences confirm those of earlier studies that found that men had longer commute times on average than women (preston and mclafferty, ; craig and van tienoven, ; brucker and rollins ; kim et al., ) . our results on commute time disparities by race/ethnicity are also consistent with earlier research showing that minorities are more likely to have long work commutes (brucker and rollins ; deka and lubin, ) . the exception is black women. their long commute times suggest that they may be less able than other groups of workers to find work close to home and accommodate gendered household responsibilities (preston and mclafferty, ) . we also find significant differences in commute time by travel mode, work location, residential location, educational attainment, public assistance status, and wage earnings. all else being equal, the average one-way commute time of public transit users is min longer than that of non-public transit users. ceteris paribus, individuals who work in manhattan commute min longer than people who work s. wong, et al. journal of transport geography ( ) elsewhere in the metropolitan region, with commute times varying based on where workers live. workers residing in the suburbs have the longest commutes. compared to workers living in the suburbs, workers residing in the center travel fewer minutes and those residing in the inner ring travel . fewer minutes. workers with a bachelor's degree or higher education have a longer commute time ( . min) than workers with less education. public assistance recipients travel . min longer than non-recipients. log hourly wages are positively correlated with commute time which indicates that overall, workers trade longer commute times to secure higher-wage employment. this fortifies what we already know -that workers who use public transit, have higher levels of education, and higher wages travel longer to get to work (preston and mclafferty, ; brucker and rollins ) . the variance in commute time attributable to the fixed and random effects differs slightly by intraurban zone. the share of the total variance explained by the fixed effects is highest in the suburbs ( . %) while similar among the other geographies (ranging from . - . %). the proportion attributable to the random effects is lowest in the center ( . %) while over % for the metro, inner ring, and suburbs (ranging from . - . %). the variances explained by the varying puma-level intercepts are sizeable relative to the variances explained by all model parameters (proportions range from to %), indicating the importance of accounting for nested data in statistical models. this section focuses on workers with disabilities alone to identify trends specific to having a disability. when using lmms to analyze commute times among workers with disabilities, we find that people are generally taking on longer commutes for higher wages across the study area (table a , model ). on average, workers with disabilities travel three minutes longer (representing % of the median commute time) for each one-unit increase in log hourly wage. then when we look closely at gender and race/ethnicity, we find that white and hispanic women have significantly shorter commute times (four and . min shorter, respectively) than comparable white men. similar disparities exist in the models for the suburbs and inner ring. among white workers with disabilities, women have shorter commutes than comparable men, reinforcing the gender gap in commuting seen in previous studies of the white population overall (preston and mclafferty, ; crane, ) . the significantly shorter commute time among hispanic women is unexpected. previous research at the state and national scales suggests that racialized minority workers with disabilities have commutes that are not significantly different from those of white, male workers farber and páez, ) . further investigation is needed to better understand this finding. specifically, we speculate whether white and hispanic women with disabilities are more likely than black women to live in neighborhoods where public transportation and job opportunities are more accessible (wong, a) . the need to consider the geographic contexts in which people with disabilities live is underscored by notable differences across the intraurban zones in the variance in commute time that is attributable to the fixed and random effects. the share of the total variance explained by the fixed effects is highest in the suburbs ( . %) and lowest in the center ( . %). the proportion attributable to the random effects is highest in the inner ring ( . %) while negligible in the center ( . %). commuting via public transit lengthens the work trips of workers with disabilities in all geographic contexts, from . min in the center to min in the suburbs and inner ring (table ) . for those who rely on public transit to get to work, access barriers in the region's subway and bus systems may result in longer travel times for workers with disabilities (bezyak et al., ; deka and lubin, ; farber and páez, ) . for disabled workers, we see reduced public transit use (and thus increased private vehicle use) from the center outward (table ) , a trend that is consistent with disabled workers' efforts to minimize public transit constraints (wong, b) . our findings of significant gender and minority disparities in commute time for disabled workers differ from those by farber and páez ( ) , which to our knowledge is the only other study to analyze how sociodemographic factors affect the commuting behavior of people with disabilities alone. using national-level data, farber and páez ( ) found that gender and minority status were not significantly correlated with commute distance for canadians with disabilities. one way to reconcile the disparate findings is to investigate in more detail how commute distance and commute time are related. people who live further away from their workplaces may travel at faster speeds that mitigate the constraint of distance (farber and páez, ) and result in commute times similar to those of residents who live closer to work. wage and commute time associations at the scale of the metropolitan region are also evident in the inner ring and suburbs, but not in the center. for each one-unit increase in log hourly wage, workers in the inner ring commute . min more (table b , model ) and workers in the suburbs travel . min longer (table b , model ). in the center, the association between wages and commute time does not reach statistical significance (table a , model ), possibly reflecting the co-location and high densities of jobs and housing in manhattan. previous research on the general population found that the highest paid workers live in manhattan where commute times are relatively short (preston and mclafferty, ) . workers with disabilities undertake longer commutes specifically for good jobs in manhattan. compared to people working in the inner ring and suburbs, those who work in manhattan have a longer commute time - min longer on average for the entire metropolitan region. commute time increases as a function of distance from the center. inner ring and suburban residents travel longer than manhattan residentsseven and min, respectively -to jobs in manhattan (table b) . our findings corroborate what we know about the population at large -on average, workers pursue longer commutes in exchange for higher wages (preston and mclafferty, ; brucker and rollins ; morris and zhou, ) . the factors that influence the commute times of workers with disabilities are similar to those for the general population. the problem that remains is that workers with disabilities are unable to make up the wage gap with longer commute times (brucker and rollins ) . our study generates new geographic insights about the impacts of disability status on wage earnings and commute times for residents in the new york metropolitan region. we extend previous research that examined national-level trends (e.g., brucker and houtenville, ; gunderson and lee, ; schur, ) by investigating metropolitan and intraurban patterns. in doing so, we uncover intraurban variability in wages and commute times that would have gone unnoticed had our analysis stopped at the metropolitan scale. when analyzing intraurban trends, we find marked variability in wage gaps between workers with and without disabilities by geographic zone, with the highest wage gaps in the center and suburbs. regarding commute time, we find that workers with disabilities have significantly longer commutes than workers without disabilities in the center and inner ring, but not in the suburbs. when looking at disabled workers alone, we find that people largely trade higher wages for longer commutes; however, such substitutions are most pronounced among workers who live in the suburbs and inner ring. gender disparities in commute time among workers with disabilities largely mimic those observed in studies of the overall population. some women may have gendered household responsibilities that motivate them to work closer to home so they can spend more time for household purposes (preston and mclafferty, ; craig and van tienoven, ) , and some women with disabilities may restrict their travels for fear of crime and uncomfortable encounters with strangers (wong, b). the notable finding is that female workers face an additional wage penalty for having a disability. it remains important to continue our collective investigations on the commute patterns of workers with disabilities because there is limited empirical evidence. our paper is one data point that joins only a few other studies (brucker and rollins ; deka and lubin, ; farber and páez, ) . more research is needed on disability and work commutes as inaccessible transportation is identified frequently as a critical obstacle to accessing employment and good jobs for people with disabilities (bezyak et al., ; lubin and feeley, ) . we anticipate that work commutes are different for people with disabilities residing in different places across the urban-rural continuum. we also expect varying travel patterns based on disability type and transportation mode. for example, some workers with mobility constraints may live close to their work locations and have short commute times. for workers with disabilities who rely on public transit, we expect long commute times. such long commute times are borne out in our study of workers with disabilities in the new york region, with its extensive public transit network. our findings underscore the need for more accessible and quicker forms of transportation as workers with disabilities are taking on the burden of longer commutes in exchange for higher wages. a more accessible public transportation system also has great potential to improve the mobility and employment rates of people with disabilities. increasing the availability of centrally located and affordable housing for people with disabilities could also enhance their access to employment. lower living costs, especially at central locations near job hubs, would help alleviate the disability pay gap and reduce commute time. at the same time, given the current covid- pandemic and the heightened risk of disease exposure from commuting via public transit and working in congregated spaces, the more immediate need may be for policies to support remote work or training for remote jobs. however, since disabled workers are usually overrepresented in service and blue-collar jobs and underrepresented in managerial and professional positions (kruse et al., ; maroto and pettinicchio, ) , they are less likely to have jobs that they can do remotely. for jobs in which working from home is not possible, there is a need for safer public transit commutes and workspaces. future research should address the limitations of this study that relies on cross-sectional data and observes trends at one time interval. longitudinal surveys, while more expensive, would provide richer information about the causal effects of disability over time. for example, jolly ( ) used longitudinal data to show that having a disability increased workers' financial precarity by increasing the probability of downward mobility in earnings, the likelihood of being at the lower end of the income distribution, and the risk of poverty. more detailed measures of disability that distinguish varying levels of impairment and include people experiencing transitory disability as well as long-term disability would also enhance our understanding of the commutes of workers with disabilities (myers et al., ) . finally, even though the sample for the new york metropolitan region is large, sample sizes for people with disabilities diminish rapidly as we disaggregate by geographic zone. a larger sample would allow even more detailed intraurban analysis. to our knowledge, ours is the first case study of intraurban wage and commute patterns among disabled workers in a major metropolitan region in the u.s. future research should study additional metropolitan areas since each region has distinctive housing and labor markets, transportation systems, and intraurban zones. an inter-urban comparison would facilitate assessment of differences and similarities in the wage and commuting trends of workers with disabilities and allow us to determine the extent to which findings in the new york metropolitan region are generalizable to other urban regions. qualitative or mixed quantitative and qualitative research has the potential to provide additional insight into the commutes of people with disabilities. qualitative studies of the commuting behavior of all workers imply that some people with disabilities are unlikely to accept a higher wage job if the commute distance is too far or the travel logistics too onerous. for example, one study utilizing mixed methods revealed that berkeley residents generally desired an acceptable wong, et al. journal of transport geography ( ) commute time, one that was contingent on people's satisfaction with various aspects of their complete travel experience (milakis et al., ) . another case study in the san francisco bay area also showed that residents with visual impairment sought reasonable work commutes as they navigated their everyday spatiotemporal constraints (wong, b) . qualitative research would help us ascertain whether the major barriers to employment and high wages are related to personal concerns, type of disability, employer discrimination, or inaccessible built environments and transportation networks. specific interventions can then be identified for improving the wage earnings, travel logistics, and overall quality of life for working-age people with disabilities. public transportation: an investigation of barriers for people with disabilities community participation and public transportation barriers experienced by people with disabilities linear mixed-effects models and the analysis of nonindependent data: a unified framework to analyze categorical and continuous independent variables that vary within-subjects and/or within-items people with disabilities in the united states the association of commuting time and wages for american workers with disabilities gender, mobility and parental shares of daily travel with and 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traveling with blindness: a qualitative space-time approach to understanding visual impairment and urban mobility this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. none. key: cord- -duvzwxv authors: džiugys, algis; bieliūnas, martynas; skarbalius, gediminas; misiulis, edagaras; navakas, robertas title: simplified model of covid- epidemic prognosis under quarantine and estimation of quarantine effectiveness date: - - journal: chaos solitons fractals doi: . /j.chaos. . sha: doc_id: cord_uid: duvzwxv a simplified model of covid- epidemic dynamics under quarantine conditions and method to estimate quarantine effectiveness are developed. the model is based on the daily growth rate of new infections when total number of infections is significantly smaller than population size of infected country or region. the model is developed on the basis of collected epidemiological data of covid pandemic, which shows that the daily growth rate of new infections has tendency to decrease linearly when the quarantine is imposed in a country (or a region) until it reaches a constant value, which corresponds to the effectiveness of quarantine measures taken in the country. the daily growth rate of new infections can be used as criteria to estimate quarantine effectiveness. the - coronavirus outbreak has started since december th, in wuhan, hubei province, people's republic of china, and has progressively expanded through almost all countries. this ongoing pandemic of coronavirus disease (covid- ) caused by severe acute respiratory syndrome coronavirus (sars-cov- ). in order to prevent the spread of the disease, many of the countries affected by the disease has been put under quarantine, which has led that , billion people ( % of whole world population) around the globe faced some form of lockdown [ ] . however, the remaining problem of the current covid- disease is that second wave of the epidemic is expected after imposed quarantine is discontinued in each country. on the basis of epidemiological data provided by european centre for disease prevention and control [ ] and estimation that the number of infections can be four times higher than the number of confirmed cases [ ] , it can be evaluated that for most countries only less than % of the population of the infected country/region will acquire the immunity after first wave of epidemic controlled by the effective quarantine. that would require next - similarly controlled waves to achieve herd (population) immunity of - % in order to stop further spread of disease. such scenario is improbable as it would require a significant amount of time, during which the individual immunity could be lost because even today, when more than . million people have been infected in more than countries and territories ( may , [ ] ), it is not clear for how long time the recovered patients have the immunity. however, hope for sars-cov- antiviral vaccine or sufficiently effective antiviral drugs, or sars-cov- virus mutation to less aggressive strain [ ] gives us chance to survive through the course of the controlled epidemic. therefore, forecasting the spread of the pandemic on the basis of mathematical models are extremely important for decisions how to prepare countries in order to avoid overloading of health system and manage other related problems. valuable information that could be obtained from modelling is forecast of the expected time and number of most active infected cases and the effectiveness of applied infection control measures. it is current global trend, that the experience and available data from already affected countries are used to model the pandemic dynamics in other countries before the epidemic has reached the peak or to estimate effectiveness of various scenario of the next wave management [ ] . most popular epidemic dynamics models of covid- are based on transmission model for a directly transmitted infectious disease, such as standard compartment models of disease sir [ , ] , or more advances derivates, such as seir and similar models [ ] [ ] [ ] [ ] . many of the models, which are used to forecast the covid- epidemic, do not accurately capture the transient dynamics of epidemics; therefore, they give poor predictions of both the epidemic's peak and its duration [ ] , because calibration of parameters are based on dynamics of such non-reliable epidemiological data as number of active infectious cases. we propose to build epidemic analysis and model on the dynamics of rate of new infection cases as more reliable epidemiological data together with an assumption of effectiveness to isolate registered infectious during imposed quarantine. other epidemiological parameters, such as numbers of active infectious, deaths, recovered, severe patients and others, can be forecasted from the forecasted dynamics of the rate of new infectious cases. the proposed approach is based on sir model. the simplest sir model consists of three compartments: s for the number of susceptible, i for the number of infectious, and r for the number of removed (recovered, deceased or immune) individuals. these variables (s, i, and r) represent the number of people in each compartment at a particular time. we denote the total population size by . the dynamics of the simplest sir system (excluding birth and death) can be described by the following set of ordinary differential equations [ ] : where γ is the rate of recovery or mortality, β is the infectious rate controlling the rate of spread that represents the probability of transmitting disease from infectious individual to susceptible individual. the disease transition rate β/ni is defined as a product of β and a probability of disease transmission during a contact between an infectious individual and a susceptible individual. in that case, is the average number of contacts per person per time unit and can be defined by the typical time between contacts = ⁄ . the transition rate between i and r defined by γ and is estimated from typical time until recovery = ⁄ . in case of isolation or self-isolation, γ can be defined by the average number of days that a person is infectious (before they are isolated or self-isolate), = ⁄ . the dynamics of the infectious class depends on the following ratio: the so-called basic reproduction number (or basic reproduction ratio) of an infection and represents the average number of infections generated by one individual over the course of the infectious period. the estimation model parameters and , as well as , may vary depending on country due to methodological issues, including different assumptions and choice of parameters, utilized models, used datasets and estimation period. in addition, during the spread of the sars-cov- virus infection, it was found that the model parameters are varying according to the dynamics of transmission of the novel coronavirus outbreak as well as the case reporting rate, which requires to build up more sophisticated and complex models [ ] .the model parameters are constantly calibrated according to the last epidemiological data because forecast is constantly refreshed. the wide and rapid spread of the disease forced many countries to impose quarantines, entry bans and other restrictions during the pandemic to reduce the movement of population and recent travellers in most affected regions [ ] . global restrictions that apply to all foreign countries and regions have also been imposed in other countries preventing their own citizens to travel overseas. these measures, especially quarantine, helped to suppress the spread of the disease within the population of various countries with different effectiveness. other important property of the pandemic is that total number of infected cases is much smaller than population size of infected country or region due to quarantine measures: this assumption allows to simplify epidemiological models used to simulate codiv- disease spread under quarantine. consequently, on the basis of eq. ( ), the parameter of sir model can be estimated as the number of new registered cases of infection to number of active cases ratio: where is the rate of new infected cases the number of daily new infected cases is defined as so, expected number of new cases in next day could be predicted by the today number of active infected individuals multiplied by the infectious rate in general, the infectious rate is time dependent and usually can be described by a complex function with additional parameters that must be daily calibrated according to last epidemiological data. behaviour of the infectious rate during quarantine may differ in different countries, which reduces possibilities to build correct model of the infectious rate on the basis of epidemiological data from other countries. furthermore, there is no clear criteria to relate influence of quarantine actions with the infectious rate . as illustration, the dynamics of the parameter estimated from active infected individuals and new cases by eq. ( ) is demonstrated in figure [ ] . in order to damp daily and weekly fluctuations, , and estimated the parameter were smoothed by moving average, where each average is calculated over a sliding window of length = days: where is any parameter to be smoothed. as can be seen, the dynamics of the parameter demonstrates similar non-linearly decreasing behaviour after the start of the quarantine for almost all countries. in addition, an estimation of the number of active infected individuals depends on the number of recovered active cases of infections , which in turn depends on testing protocols, tests number, delays in testing and other circumstances, which are different in each country. consequently, this makes = − unreliable parameter for model calibration. for example, in lithuania the first pool consisting of recovered cases of total cases was reported only after days from the first infection registration [ ] , which can be explained only by troubles in recording of recovered cases and can be also expected in other countries. in contrary, the number of daily new infected cases , despite of countries specificity, is still the most reliable parameter allowing to estimate disease spreading. in addition, other epidemiological parameters, such as numbers of active infectious, deaths, recovered, severe patients and others, can be forecasted from the forecasted dynamics of the number of daily new infectious cases. in order to build model of covid- disease spread during quarantine, we make simplifying assumptions, that:  registered infected individuals do not spread virus to health individuals, because of an effective isolation of the registered infected individuals;  no imported infections. new cases of infectious individuals are generated by previously infectious individuals until they are registered; therefore, the number of new cases of the day is dependent on the number of new cases generated during previous day and the effectiveness of imposed quarantine actions: ) restriction of social contacts and mobility, ) identification of infectious individual and his contact tracing as soon as possible, ) isolation of infectious individuals. let us analyse hypothetical simplified case. the averaged time period, during which an infected individual is registered and isolated after infection, is denoted . during this time period, the infected individual is infectious and infects individuals. in the end of this period, the infected individual is isolated and does not take more participation in the process of the epidemic spread. during the time period [ − , ], new infected cases are generated, from which ( − , ) are registered and isolated. these new registered infected cases will then generate more cases and the number of new registered infection cases for next time period [ , + ]: where is the growth rate of new cases and can be associated with the effective reproduction number [ ] . the parameter is time dependent and > means that number of new cases is increasing, while < -decreasing. according to eq. ( ), the parameter can expressed as follows: it is evident that in limits of → , we have which, together with eq. ( ), gives differential equation for disease dynamics during quarantine: keeping in mind eqs. ( ) and ( ), the parameter can be related to the infectious rate as follows let us define as the growth rate of new infection cases when epidemic starts and spreads without control. because of > , the number of new cases is exponentially increasing. it is expected that the population in any country would start to behave more safely even though no official quarantine actions were taken; consequently, the growth rate of new cases is expected to slowly decrease before strict quarantine rules are imposed. the growth rate of new infected cases can be defined as = ( = ) > at the quarantine start time = . because of > , the number of new cases is still increasing. let us assume that the imposed quarantine is ideally effective, which means that all infected individuals are isolated until the end of the time span and do not have contact with other individuals during time span [ , + ]. furthermore, no new cases will be generated for the next time period [ + , + ]. in such case, the growth rate of new cases becomes constant and equal to after the quarantine starts: ( > ) = = (figure (a) ), which means that the supposed effectiveness of the quarantine is equal to and epidemic is stopped immediately. if the quarantine is less effective, then the growth rate of new cases is non zero constant ( > ) = > , which leads to slower spread of the disease in case of > > and suppression of the epidemic in case of > > (figure (b) ). consequently, quarantine effectiveness can be measured as the zero effectiveness = means that the growth rate of new cases during quarantine remains the same as before: = . therefore, in order to suppress the disease, the growth rate of new cases must be below , which means that quarantine effectiveness must be greater than − ⁄ . in realistic scenario, the growth rate of new cases does not change sharply at the time because of time lag due to incubation period, infections generated by non-registered infected individuals and so on. in addition, it takes a time for people to adjust to the quarantine requirements after the beginning of the quarantine; therefore, there is a time lag before people start to strictly follow the rules. consequently, the growth rate of new cases decreases from initial value until reaches constant value satisfying the effectiveness of applied quarantine at the time ( figure ). − depends on the properties of covid- disease, such as incubation period and time span of individual being infectious, and how quickly quarantine actions are implemented. as a result, the angle = − (( − ) ( − ) ⁄ ) depends on − and the effectiveness of applied quarantine actions, because the case of = corresponds to situation when applied measures does not improve quarantine effectiveness and remains constant. the case of approaching to demonstrates exceptional effectiveness of the applied measures. negative corresponds to increasing the growth rate of new cases , what signalizes about critical state of broken quarantine. in addition, for a big country with heterogeneous population distribution across the country, it is expected to have several infection clusters and, therefore, wider time period − will be for decreasing stage (and consequently sharper φ) due to different start time of disease in each infection cluster. so, angle φ depends on the quarantine effectiveness, durations specific for the disease and homogeneity of the infected country or region. the proposed parameters and together with analysis of the population mobility and social contacts [ ] can be used to estimate effectiveness of country or region lockdown measures. in this paper we will analyse only . in order to predict covid- disease spread in infected country or region with imposed quarantine, a model of the growth rate of new cases needs to be developed. it is possible to build up such model speculatively in general; however, it is reasonable to analyse dynamics of in various countries. we analysed covid- pandemic data from various countries [ , ] . the daily growth rate of new infection cases was estimated on the basis of the registered daily new infection cases , ( ) (defined by eq. ( )) and smoothed by moving average according to eq. ( ) with sliding window of length = days in order to damp daily and weekly fluctuations: in this case, the parameter ( ) can be interpreted as the average daily reproduction number [ ] . as illustration, the dynamics of ⟨ ⟩, obtained as the parameter smoothed by moving average according to eq. ( ) with sliding window of length = days, is demonstrated in figure as can be seen, that despite of fluctuations, the scenario described in figure can be identified in the dynamics of the parameter : chaotic behaviour of before quarantine demonstrates linear decreasing until some certain value after quarantine. let us analyse some examples in greater detail. ) is presented in figure (b) by solid blue line. if to average fluctuations over supposed straights, the daily growth rate of new cases was almost constant or slowly decreasing before quarantine, started to decrease sufficiently after quarantine had been imposed and had somewhat linear dependency on time during quarantine time, which allowed to approximate by descending straight line ( figure consequently, the model of the daily growth rate of new cases can be described as follows: where = . is value in the beginning of the quarantine occasional new infections occurring during last weeks demonstrate that efficiency of applied quarantine actions was sufficient to suppress substantially the epidemic in the country, but the effectiveness is still not enough to decimate the infection. let us note, that small numbers of daily new infection cases ( < ) are registered after ′ = days, and therefore, the proposed method cannot not be used for such small numbers, because of too casual nature of new infections. consequently, the epidemic end cannot be forecasted accurately. we will shortly overview some other countries demonstrating applicability and possible shortcomings of the proposed approach. the next example of the similar scenario is switzerland. the government of switzerland announced that no lockdown would be implemented; however, some restrictions were implemented [ ] . on march , the federal council decided to cancel classes in all educational establishments until april and banned all events (public or private) involving more than people. furthermore, the borders were closed, and border control was enacted. on march , the federal council announced further measures and a revised ordinance. measures included the closure of bars, shops and other gathering places until april , but leaved open certain essentials, such as grocery shops, pharmacies, (a reduced) public transport and the postal service. since march , all events or meetings over people were prohibited, and economic activities would continue including construction. the daily growth rate of new cases began decreased before first official restrictions of social contacts (figure (b) ) while daily numbers of new cases were relatively small. during three following weeks after the restrictions initiation, continued to decrease from . on march until . and it is expected for to remain constant until the end of the epidemic ( figure ). [ ] and the calculated growth rate of new cases are presented in figure . the modelled was overestimated (figure (b)), because was approximated by one straight in the time interval from (corresponding to march ) to = + days (figure (a) ). to improve the model of , the change of alert level from to on fifth day after the beginning of the quarantine must be considered. accordingly, must be approximated by straights in the time interval [ , ] . the similar scenario is demonstrated in iceland, where universities and secondary schools were closed on march . furthermore, public gatherings of over were banned on the same day [ ]. the same quarantine conditions were applied for the whole quarantine period. nevertheless, there were three stages during the time interval [ , ], = + days (figure (b) ). the first stage of decreasing lasted for days since the beginning of the quarantine. then the next stage followed up for days, in which the fluctuates around ≈ . the third and the final stage of decreasing took place for days, during which reached value of = . . therefore, model for the whole period of days, which describes the behaviour of by one decreasing line the similar scenario to australia and switzerland cases developed in austria (figure ) , where the epidemic started on february , and the quarantine was imposed on march [ ] . however, slight increase of the daily growth rate after one month of quarantine may be related to the easter celebration, which started after good friday, april . after the easter, the number of daily new cases fluctuates around cases per day. the case of poland illustrates the scenario when the proposed method to predict epidemic dynamics under quarantine does not work straightforward, because of country specificity. strict rules of the country lockdown were implemented on march [ ], and it was expected, that quarantine effectiveness would be the same as in the cases described above. however, during four following weeks after the beginning of the quarantine, decreased from . only to . and then stayed fluctuating around ≈ till now ( may ) (figure ) , what shows the low effectiveness of the taken quarantine actions. as in austria case, the most reliable reason is the easter celebration. during the expected next wave of the covid- , such specificity of the country can be taken in to account. italy has been under quarantine since march , [ ] . it seems that italians are too tired of the country lockdown, that they have strong intentions to finish the lock-down as soon as possible. therefore, italy celebrated the easter more quietly without visible breaks of the quarantine restrictions ( figure ). however, a high value of the daily growth rate of new infection cases during the imposed quarantine = . suggests that quarantine actions are not sufficient and, there is little hope to reach the end of epidemic as fast as australia having = . . denmark is an example in which the proposed model cannot be applied to predict the epidemic dynamics, and clarification of the reasons for such discrepancy requires more detailed analysis of epidemic situation in the country ( figure ) . however, the last days is below , what demonstrates that social distancing helps to reduce infection rate. situation in russia serves as an example of ineffective quarantine actions for at least first two weeks of the country lockdown. this can be explained by huge size of the country and heterogeneous distribution of the population across the country, which is reason for sequence of arising infection clusters in different locations/regions at different times, despite that national quarantine was imposed on march, . consequently, the daily growth rate of new infection cases = . remained above for days with almost zero angle of inclination = − ( ) ≈ (figure (b) ), what demonstrates that effectiveness of the quarantine actions was insufficient during this period. for example, only from may, moscow's residents will be required to wear face masks and gloves in public transport and public places [ ] , while face masks in public places are one of the most important obstacles for virus spread [ ] . consequently, the daily growth rate crossed critical value = only after days from the national lockdown start, but it gives hope that eventually the epidemic reached peak of the daily new infection cases . because of heterogeneous distribution of the population, analysis and forecasting of epidemic situation must be done at region level to generate results with practical value. like russia, united states of america is another huge country by the population number and size. the dynamics of the new cases and the daily growth rate of new infection cases fluctuating around ≈ till now in usa show that quarantine is not effective enough ( figure ) and suggested emergence of new clusters of infection. the forecast, made on the basis of the current dynamics of the epidemic, shows that epidemic will not be defeated in the usa until the end of this year. it should be taken into account, that differences of covid- statistics across various states are huge: cases per people are varying more than times [ ] . therefore, overall us data can suffer from too high level of generalisation. again as in russia, analysis and forecasting of epidemic situation should be done at state level to generate results with practical value. scenario realised in sweden, where the quarantine started on march, [ ], is specific. due to soft conditions of the quarantine (technically most of eu countries would not attribute swedish regime a quarantine, just a gradual restriction of some social activities), it seems that the new cases is achieved maximum only in weeks days after the lockdown start and then the stabilised at = (figure ). further dynamics of the epidemic is still unclear because no country has experience of such situation. the experience gained in sweden is very important and will be used by other countries for the second wave management in the future. the experience gained during the first wave of covid- pandemic could help countries to be better prepared for the next wave, which is expected to take place in the autumn of . we proposed the simplified approach, which allows to quantifiable estimate effectiveness of the imposed quarantine conditions/restrictions and compare between countries, forecast the epidemic spread and take appropriate decisions. the proposed approach is based on the time series data of registered daily infection rate as most reliable epidemiological data together with the following main assumptions:  total number of infections is much smaller than a population size of the infected country or region;  registered infected individuals are effectively isolated during the imposed quarantine. the observed dynamics of the pandemic in examined countries shows that the daily growth rate of new infection cases has a tendency to decrease linearly during the imposed quarantine period until reaching a constant value, which corresponds to the effectiveness of taken quarantine measures in the country. the proposed parameters , and together with the analysis of the population mobility and social contacts can be used to estimate the effectiveness of the lockdown measures. on the basis of these parameters, the countries experiencing ongoing epidemic can use the proposed approach to study effectiveness of taken quarantine measures in other countries yet affected by the covid- disease. the proposed approach has a limitation because it cannot be directly applied for a country with large population size, which might have several epidemic clusters due to the heterogeneous population distribution across the country. in this case, each cluster must be analysed separately. also, the approach cannot be applied when the daily infection cases is too few because of casual nature of emerging new infections. consequently, the epidemic finish cannot be forecasted accurately. on the basis of the proposed approach, more complex models of epidemic forecasting can be developed. a demographic scaling model for estimating the total number of covid- infections on the origin and continuing evolution of sars-cov- quantifying the effect of quarantine control in covid- infectious spread using machine learning the sir model and the foundations of public health modelling the covid- epidemic and implementation of population-wide interventions in italy an seir infectious disease model with testing and conditional quarantine nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study the mathematics of infectious diseases stability of epidemic models with waning immunity dynamics of covid- epidemics: seir models underestimate peak infection rates and overestimate epidemic duration an updated estimation of the risk of transmission of the novel coronavirus ( -ncov) joint european roadmap towards lifting covid- containment measures novel coronavirus (covid- ) cases data n svarbiausia informacija apie koronavirusą (covid- ) n.d different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures see how your community is moving around differently due to covid- n Частичное возобновление работы, масочный и перчаточный режим wearing face masks in the community during the covid- pandemic: altruism and solidarity n tracking the pandemic: how quickly is the coronavirus spreading state by state? n data availability the data used to support the findings of this study are available from the corresponding author upon request. data for the infected cases count from various countries is obtained from the data we also would like to thank tadas markūnas and aušra džiugytė for collecting of covid- epidemiological data. ad developed the method, analysed data and post-process data. mb proposed the conception of the model and analysed data. gs, em and rn performed data processing. all authors wrote and approved the manuscript. we declare no competing interests. correspondence and requests for materials should be addressed to ad.declaration of interests + the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐the authors declare the following financial interests/personal relationships which may be considered as potential competing interests: key: cord- -ikepr p authors: tulchinsky, theodore h.; varavikova, elena a. title: expanding the concept of public health date: - - journal: the new public health doi: . /b - - - - . - sha: doc_id: cord_uid: ikepr p ancient societies recognized the needs of sanitation, food safety, workers’ health, and medical care to protect against disease and to promote well-being and civic prosperity. new energies and knowledge since the eighteenth century produced landmark discoveries such as prevention of scurvy and vaccination against smallpox. the biological germ theory and competing miasma theory each proved effective in sanitation, and immunization in control of infectious diseases. non-communicable diseases as the leading causes of mortality have responded to innovative preventive care of health risk factors, smoking, hypertension, obesity, physical inactivity, unhealthful diets, and diabetes mellitus. health promotion proved effective to modern public health in tackling disease origins, individual behavior, and social and economic conditions. the global burden of infectious and non-communicable diseases, aging and chronic illness faces rising costs and still inadequate prevention. the evolution of concepts of public health will have to address these new challenges of population health. the development of public health from its ancient and recent roots, especially in the past several centuries, is a continuing process, with evolutionary and sometimes dramatic leaps forward, and important continuing and new challenges for personal and population health and well-being. everything in the new public health is about preventing avoidable disease, injuries, disabilities, and death while promoting and maximizing a healthy environment and optimal conditions for current and future generations. thus, the new public health addresses overall health policy, resource allocation, as well as the organization, management, and provision of medical care and of health systems in general within a framework of overall social policy and in a community, state, national, transnational, and global context. the study of history (see chapter ) helps us to understand the process of change, to define where we came from and where we are going. it is vital to recognize and understand change in order to deal with radical transformations in direction that occur as a result of changing demography and epidemiology, new science, evolving best practices in public health and clinical medicine, and above all inequalities in health resulting from societal system failures and social and economic factors. health needs will continue to develop in the context of environmental, demographic and societal adjustments, with knowledge gained from social and physical sciences, practice, and economics. for the coming generations, this is about not only the quality of life, but the survival of society itself. over the past century there have been many definitions of public health and health for all. mostly they represent visions and ideals of societal and global aspirations. this chapter examines the very base of the new public health, which encompasses the classic issues of public health with recognition of the advances made in health promotion and the management of health care systems as integral components of societal efforts to improve the health of populations and of individuals. what follows in succeeding chapters will address the major concepts leading to modern and comprehensive elements of public health. inevitably, concepts of public health continue to evolve and to develop both as a philosophy and as a structured discipline. as a professional field, public health requires specialists trained with knowledge and appreciation of its evolution, scientific advances, concepts, and best practices, old and modern. it demands sophisticated professional and managerial skills, the ability to address a problem, reasoning to define the issues, and to advocate, initiate, develop, and implement new and revised programs. it calls for profoundly humanistic values and a sense of responsibility towards protecting and improving the health of communities and every individual. in the twenty-first century, this set of values was well expressed in the human development index agreed to by nations (box . ). public health is a multidimensional field and therefore multidisciplinary in its workforce and organizational needs. it is based on scientific advances and application of best practices as they evolve, and includes many concepts, including holistic health, first established in ancient times. the discussion will return to the diversity of public health throughout this chapter and book many times. in previous centuries, public health was seen primarily as a discipline which studies and implements measures for control of communicable diseases, primarily by sanitation and vaccination. the sanitary revolution, which preceded the development of modern bacteriology, made an enormous contribution to improved health, but many other societal factors including improved nutrition, education, and housing were no less important for population health. maternal and child health, occupational health, and many other aspects of a growing public health network of activities played important roles, as have the physical and social environment and personal habits of living in determining health status. in recent decades recognition of the importance of women's health and health inequalities associated with many high-risk groups in the population have seen both successes and failures in addressing their challenges. male health issues have received less attention, apart from issues associated with specific diseases, or those of healthy military personnel. the scope of public health has changed along with growth of the medical, social, and public health sciences, public expectations, and practical experience. taken together, these have all contributed to changes in the concepts and causes of disease. health systems that fail to adjust to changes in fundamental concepts of public health suffer from immense inequity and burdens of preventable disease, disability, and death. this chapter examines expanding concepts of public health, leading to the development of a new public health. public health has evolved as a multidisciplinary field that includes the use of basic and applied science, education, social sciences, economics, management, and communication skills to promote the welfare of the individual and the community. it is greater than the sum of its component elements and includes the art and politics of the funding and coordination of the wide diversity of community and individual health services. the concept of the interdependence of health in body and in mind has ancient origins. they continue to be fundamental to individuals and societies, and part of the fundamental rights of all humans to have knowledge of healthful lifestyles and to have access to those measures of good health that society alone is able to provide, such as immunization programs, food and drug safety and quality standards, environmental and occupational health, and universal access to high-quality primary and specialty medical and other vital health services. this holistic view of balance and equilibrium may be a renaissance of classical greek and biblical traditions, applied with the broad new knowledge and experience of public health and medical care of the nineteenth, twentieth, and the early years of the twenty-first centuries as change continues to challenge our capacity to adapt. the competing nineteenth-century germ and miasma theories of biological and environmental causation of illness each contributed to the development of sanitation, hygiene, immunization, and understanding of the biological and social determinants of disease and health. they come together in the twenty-first century encompassed in a holistic new public health addressing individual and population health needs. medicine and public health professionals both engage in organization and in direct care services. these all necessitate an understanding of the issues that are included in the new public health, how they evolved, interact, are put together in organizations, and are financed and operated in various parts of the world in order to understand changes going on before our eyes. great success has been achieved in reducing the burden of disease with tools and concepts currently at our disposal. the idea that this is an entitlement for everyone was articulated in the health for all concept of alma-ata in . the health promotion movement emerged in the s and showed dramatically effective results in managing the new human immunodeficiency virus (hiv) pandemic and in tackling smoking and other risk factors for non-communicable diseases (ncds). a health in all policy concept emerged in promoting the concept that health should be a basic component of all public and private policies to achieve the full potential of public health and eliminate inequalities associated with social and economic conditions. profound changes are taking place in the world population, and public health is crucial to respond accordingly: mass migration to the cities, fewer children, extended life expectancy, and the increase in the population of older people who are subject to more chronic diseases and disabilities in a changing physical, social, and economic climate. health systems are challenged with continuing development of new medical technologies and related reforms in clinical practice, while experiencing strong influences of pharmaceuticals and the medicalization of health, with prevention and health promotion less central in priorities and resource allocation. globalization of health has many meanings: international trade, improving global communications, and economic changes with increasing flows of goods, services, and people. ecological and climate change bring droughts, hurricanes, arctic meltdown, and rising sea levels. globalization also has political effects, with water and food shortages, terrorism, and economic distress affecting billions of people. in terms of health, disease can spread from one part of the world to others, as in pandemics or in a quiet spread such as that of west nile fever moving from its original middle eastern natural habitat to the americas and europe, or severe acute respiratory syndrome (sars), which spread with lightning speed from chinese villages to metropolitan cities such as toronto, canada. it can also mean that the ncds characteristic of the industrialized countries are now recognized as the leading causes of death in low-and middle-income countries, associated with diet, activity levels, and smoking, which are themselves pandemic risk factors. the potential for global action in health can also be dramatic. the eradication of smallpox was a stunning victory for public health. the campaign to eradicate poliomyelitis is succeeding even though the end-stage is fraught with setbacks, and measles elimination has turned out to be more of a challenge than was anticipated a decade ago, with resurgence in countries thought to have it under control. global health policies have also made the achievements of public-private partnerships of great importance, particularly in vaccination and acquired immunodeficiency syndrome (aids) control programs. there have been failures as well, with very limited progress in human resources development of the public health workforce in low-income countries. the new public health is necessarily comprehensive in scope and it will continue to evolve as new technologies and scientific discoveries -biological, genetic, and sociological -reveal more methods of disease control and health promotion. it relates to or encompasses all community and individual activities directed towards improving the environment for health, reducing factors that contribute to the burden of disease, and fostering those factors that relate directly to improved health. its programs range broadly from immunization, health promotion, and child care, to food labeling and fortification, as well as to the assurance of well-managed, accessible health care services. a strong public health system should have adequate preparedness for natural and human-made disasters, as seen in the recent tsunamis, hurricanes, biological or other attacks by terrorists, wars, conflicts, and genocidal terrorism (box . ) . the concepts of health promotion and disease prevention are essential and fundamental elements of the new public health. parallel scientific advances in molecular biology, genetics and pharmacogenomics, imaging, information technology, computerization, biotechnology, and nanotechnology hold great promise for improving the productivity of the health care system. advances in technology with more effective and less expensive drug and vaccine development, with improved safety and effectiveness, and fewer adverse reactions, will over time greatly increase efficiency in prevention and treatment modalities. the new public health is important as a conceptual base for training and practice of public health. it links classical topics of public health with adaptation in the organization and financing of personal health services. it involves a changed paradigm of public health to incorporate new advances in political, economic, and social sciences. failure at the political level to appreciate the role of public health in disease control holds back many societies in economic and social development. at the same time, organized public health systems need to work to reduce inequities between and inside countries to ensure equal access to care. it also demands special attention through health promotion activities of all kinds at national and local societal levels to provide access for groups with special risks and needs to medical and community health care with the currently available and newly developing knowledge and technologies. the great gap between available capabilities to prevent and treat disease and actually reaching all in need is still the the mission of the nph is to maximize human health and well-being for individuals and communities, nationally and globally. the methods with which the nph works to achieve this are in keeping with recognized international best practices and scientific advances: . societal commitment and sustained efforts to maximize quality of life and health, economic growth with equity for all (health for all and health in all). collaboration between international, national, state, and local health authorities working with public and private sectors to promote health awareness and activities essential for population health. . health promotion of knowledge, attitudes, and practices, including legislation and regulation to protect, maintain, and advance individual and community health. . universal access to services for prevention and treatment of illness and disability, and promotion of maximum rehabilitation. . environmental, biological, occupational, social, and economic factors that endanger health and human life, addressing: (a) physical and mental illness, diseases and infirmity, trauma and injuries (b) local and global sanitation and environmental ecology (c) healthful nutrition and food security including availability, quality, safety, access, and affordability of food products (d) disasters, natural and human-made, including war, terrorism, and genocide (e) population groups at special risk and with specific health needs. . promoting links between health protection and personal health services through health policies and health systems management, recognizing economic and quality standards of medical, hospital, and other professional care in health of individuals and populations. . training of professional public health workforces and education of all health workers in the principles of ethical best practices of public health and health systems. . research and promotion of current best practices: wide application of current international best practices and standards. . mobilizing the best available evidence from local and international scientific and epidemiological studies and best practices recognized as contributing to the overall goal. . maintaining and promoting equity for individual and community rights to health with high professional and ethical standards. source of great international and internal national inequities. these inequities exist not only between developed and developing countries, but also within transition countries, mid-level developing countries, and those newly emerging with rapid economic development. the historical experience of public health will help to develop the applications of existing and new knowledge and societal commitment to social solidarity in implementation of the new discoveries for every member of the society, despite socioeconomic, ethnic, or other differences. political will and leadership in health, adequate financing, and organization systems in the health setting are crucial to furthering health as an objective with defined targets, supported by well-trained staff for planning, management, and monitoring the population health and functioning of health systems. political leadership and professional support are both indispensable in a world of limited resources, with high public expectations and the growing possibilities of effectiveness of public health programs. well-developed information and knowledge management systems are required to provide the feedback and information needed for good management. it includes responsibilities and coordination at all levels of government. non-governmental organizations (ngos) and participation of a well-informed media and strong professional and consumer organizations also have significant roles in furthering population health. no less important are clear designations of responsibilities of the individual for his or her own health, and of the provider of care for humane, high-quality professional care. the complexities and interacting factors are suggested in figure . , with the classic host-agent-environment triad. many changes have signaled a need for transformation towards the new public health. religion, although still a major political and policy-making force in many countries, is no longer the central organizing power in most societies. organized societies have evolved from large extended families and tribes to rural societies, cities, regions, and national governments. with the growth of industrialized urban communities, rapid transport, and extensive trade and commerce in multinational economic systems, the health of individuals and communities has become more than just a personal, family, and/or local problem. an individual is not only a citizen of the village, city, or country in which he or she lives, but a citizen of a "global village". the agricultural revolutions and international explorations of the fifteenth to seventeenth centuries that increased food supply and diversity were followed only much later by knowledge of nutrition as a public health issue. the scientific revolution of the seventeenth to nineteenth centuries provided the basics to describe and analyze the spread of disease and the poisonous effects of the industrial revolution, including crowded living conditions and pollution of the environment with serious ecological damage. in the latter part of the twentieth century, a new agricultural "green revolution" had a great impact in reducing human deprivation internationally, yet the full benefits of healthier societies are yet to be realized in the large populations living in abject poverty in sub-saharan africa, south-east asia, and other parts of the world. global water shortages can be addressed with new methods of irrigation, water conservation and the application of genetic sciences to food production, and issues of economics and food security are of great importance to a still growing world population with limited supplies. further, food production capacity can and must be enlarged to meet current food insecurity, rising expectations of developing nations, and population growth. the sciences of agriculture-related fields, including genetic sciences and practical technology, will be vital to human progress in the coming decades. these and other societal changes discussed in chapter have enabled public health to expand its potential and horizons, while developing its pragmatic and scientific base. organized public health in the twentieth century proved effective in reducing the burden of infectious diseases and has contributed to improved quality of life and longevity by many years. in the last half-century, chronic diseases have become the primary causes of morbidity and mortality in the developed countries and increasingly in developing countries. growing scientific and epidemiological knowledge increases the capacity to deal with these diseases. many aspects of public health can only be influenced by the behavior of and risks to the health of individuals. these require interventions that are more complex and relate to societal, environmental, and community standards and expectations as much as to personal lifestyle. the dividing line between communicable and non-communicable diseases changes over time. scientific advances have shown the causation of chronic conditions by infectious agents and their prevention by curing the infection, as in helicobacter pylori and peptic ulcers, and in prevention of cancer of the liver and cervix by immunization for hepatitis b and human papillomavirus (hpv), respectively. chronic diseases have come to the center stage in the "epidemiological transition", as infectious diseases came under increasing control. this, in part, has created a need for reform in the funding and management of health systems due to rapidly rising costs, aging of the population, the rise of obesity and diabetes and other chronic conditions, mushrooming therapeutic technology, and expanding capacity to deal with public health emergencies. reform is also needed in international assistance to help less developed nations build the essential infrastructure to sustain public health in the struggle to combat aids, malaria, tuberculosis (tb), and the major causes of preventable infant, childhood, and motherhood-related deaths. the nearly universal recognition of the rights of people to have access to health care of acceptable quality by international standards is a challenge of political will and leadership backed up by adequate staffing with public health-trained staff and organizations. the challenges of the current global economic crisis are impacting social and health systems around the world. the interconnectedness of managing health systems is part of the new public health. setting the priorities and allocating resources to address these challenges requires public health training and orientation of the professionals and institutions participating in the policy, management, and economics of health systems. conversely, those who manage such institutions are recognizing the need for a wide background in public health training in order to fulfill their responsibilities effectively. concepts such as objectives, targets, priorities, cost-effectiveness, and evaluation have become part of the new public health agenda. an understanding of how these concepts evolved will help the future health provider or manager to cope with the complexities of mixing science, humanity, and effective management of resources to achieve higher standards of health, and to cope with new issues as they develop in the broad scope of the new public health for the twenty-first century, in what breslow called the "third public health era" of long and healthy quality of life (box . ). health can be defined from many perspectives, ranging from statistics on mortality, life expectancy, and morbidity rates to idealized versions of human and societal perfection, as in the world health organization's (who's) founding charter. the first public health era -the control of communicable diseases. second public health era -the rise and fall of chronic diseases. third public health era -the development of long and high-quality life. preamble to the constitution of the who, as adopted by the international health conference in new york in and signed by the representatives of states, entered into force on april , with the widely cited definition: "health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity". this definition is still important conceptually as an ideal accepted as fundamental to public policy over the years. a more operational definition of health is a state of equilibrium of the person with the biological, physical, and social environment, with the object of maximum functional capability. health is thus seen as a state characterized by anatomical, physiological, and psychological integrity, and an optimal functional capability in the family, work, and societal roles (including coping with associated stresses), a feeling of well-being, and freedom from risk of disease and premature death. deviances in health are referred to as unhealthy and constitute a disease nomenclature. there are many interrelated factors in disease and in their management through what is now called risk reduction. in , claude bernard described the phenomenon of adaptation and adjustment of the internal milieu of the living organism to physiological processes. this concept is fundamental to medicine. it is also central to public health because understanding the spectrum of events and factors between health and disease is basic to the identification of contributory factors affecting the balance towards health, and to seeking the points of potential intervention to reverse the imbalance. as described in chapter , from the time of hippocrates and galen, diseases were thought to be due to humors and miasma or emanations from the environment. this was termed the miasma theory, and while without a direct scientific explanation, it was acted upon in the early to mid-nineteenth century and promoted by leading public health theorists including florence nightingale, with practical and successful measures to improve sanitation, housing, and social conditions, and having important results in improving health conditions. the competing germ theory developed by pioneering nineteenthcentury epidemiologists (panum, snow, and budd), scientists (pasteur, cohn, and koch), and practitioners (lister and semmelweiss) led to the science of bacteriology and a revolution in practical public health measures. the combined application of the germ (agent-host-environment) and miasma theories (social and sanitary environment) has been the basis of classic public health, with enormous benefits in the control of infectious and other diseases or harmful conditions. the revolutionary changes occurring since the s have brought about a decline in cardiovascular and cancer mortality, and conceptual changes such as health for all and health in all to bring health issues to all policies at both governmental and individual levels. the concepts of public health advanced with the marc lalonde health field concept (new perspectives on the health of canadians, ) , stating that health was the result of the physical and social environment, lifestyle and personal habits, genetics, as well as organization and provision of medical care. the lalonde report was a key concept leading to ideas advanced at the alma-ata conference on primary care held in and more explicitly in the development of the basis for health promotion as articulated in the ottawa charter of on health promotion. this marked the beginning of a whole new aspect of public health, which proved itself in addressing with considerable success the epidemic of hiv and cardiovascular diseases. in the usa, the surgeon general's reports of on smoking and health, and of defining health targets as national policy promoted the incorporation of "management by objectives" from the business world applied to the health sector (see chapter ). this led to healthy people usa and later versions, and the united nations (un) millennium development goals (mdgs), aimed primarily at the middle-and low-income countries (box . ). the identification of infectious causes of cancers of the liver and cervix established a new paradigm in epidemiology, and genetic epidemiology has important potential for public health and clinical medicine. in the basic host-agent-environment paradigm, a harmful agent comes through a sympathetic environment into contact with a susceptible host, causing a specific disease. this idea dominated public health thinking until the midtwentieth century. the host is the person who has or is at risk for a specific disease. the agent is the organism or direct cause of the disease. the environment includes the external factors which influence the host, his or her susceptibility to the agent, and the vector which transmits or carries the agent to the host from the environment. this explains the causation and transmission of many diseases. this paradigm (figure . ), in effect, joins together the contagion and miasma theories of disease causation. a specific agent, a method of transmission, and a susceptible host are involved in an interaction, which are central to the infectivity or severity of the disease. the environment can provide the carrier or vector of an infective (or toxic) agent, and it also contributes factors to host susceptibility; for example, unemployment, poverty, or low education level. the expanded host-agent-environment paradigm widens the definition of each of the three components ( figure . ), in relation to both acute infectious and chronic noninfectious disease epidemiology. in the latter half of the twentieth century, this expanded host-agent-environment paradigm took on added importance in dealing with the complex of factors related to chronic diseases, now the leading causes of disease and premature mortality in the developed world, and increasingly in developing countries. interventions to change host, environmental, or agent factors are the essence of public health. in infectious disease control, the biological agent may be removed by pasteurization of food products or filtration and disinfection (chlorination) of water supplies to prevent transmission of waterborne disease. the host may be altered by immunization to provide immunity to a specific infective organism. the environment may be changed to prevent transmission by destroying the vector or its reservoir of the disease. a combination of these interventions can be used against a specific risk factor, toxic or nutritional deficiency, infectious organism, or disease process. vaccine-preventable diseases may require both routine and special activities to boost herd immunity to protect the individual and the community. for other infectious diseases for which there is no vaccine (e.g., malaria), control involves a broad range of activities including case finding and treatment to improve the individual's health and to reduce the reservoir of the disease in the population, and other measures such as bed nets to reduce exposure of the host to vector mosquitoes, as well as vector control to reduce the mosquito population. tb control requires not only case finding and treatment, but understanding the contributory factors of social conditions, diseases with tb as a secondary condition (substance abuse and aids), agent resistance to treatment, and the inability of patients or carriers to complete treatment without supervision. sexually transmitted infections (stis) which are not controllable by vaccines require a combination of personal behavior change, health education, medical care, and skilled epidemiology. with non-infectious diseases, intervention is even more complex, involving human behavior factors and a wide range of legal, administrative, and educational issues. there may be multiple risk factors, which have a compounding effect in disease causation, and they may be harder to alter than infectious diseases factors. for example, smoking in and of itself is a risk factor for lung cancer, but exposure to asbestos fibers has a compounding effect. preventing exposure to the compounding variables may be easier than smoking cessation. reducing trauma morbidity and mortality is equally problematic. the identification of a single specific cause of a disease is of great scientific and practical value in modern public health, enabling such direct interventions as the use of vaccines or antibiotics to protect or treat individuals from infection by a causative organism, toxin, deficiency condition, or social factor. the cumulative effects of several contributing or risk factors in disease causation are also of great significance in many disease processes, in relation to infectious diseases such as nutritional status as for chronic diseases such as the cardiovascular group. the health of an individual is affected by risk factors intrinsic to that person as well as by external factors. intrinsic factors include the biological ones that the individual inherits and those life habits he or she acquires, such as smoking, overeating, or engaging in other high-risk behaviors. external factors affecting individual health include the environment, the socioeconomic and psychological state of the person, the family, and the society in which he or she lives. education, culture, and religion are also contributory factors to individual and community health. there are factors that relate to health of the individual in which the society or the community can play a direct role. one of these is provision of medical care. another is to ensure that the environment and community services include safety factors that reduce the chance of injury and disease, or include protective measures; for example, fluoridation of a community water supply to improve dental health, and seat-belt or helmet laws to reduce motor vehicle injury and death. these modifying factors may affect the response of the individual or the spread of an epidemic (see chapter ). an epidemic may also include chronic disease, because common risk factors may cause an excess of cases in a susceptible population group, in comparison to the situation before the risk factor appeared, or in comparison to a group not exposed to the risk factor. these include rapid changes or "epidemics" in such conditions as type diabetes, asthma, cardiovascular diseases, trauma, and other non-infectious disorders. disease is a dynamic process, not only of causation, but also of incubation or gradual development, severity, and the effects of interventions intended to modify outcome. knowledge of the natural history of disease is fundamental to understanding where and with what means intervention can have the greatest chance for successful interruption or change in the disease process for the patient, family, or community. the natural history of a disease is the course of that disease from beginning to end. this includes the factors that relate to its initiation; its clinical course leading up to resolution, cure, continuation, or long-term sequelae (further stages or complications of a disease); and environmental or intrinsic (genetic or lifestyle) factors and their effects at all stages of the disease. the effects of intervention at any stage of the disease are part of the disease process (figure . ). as discussed above, disease occurs in an individual when agent, host, and environment interact to create adverse conditions of health. the agent may be an infectious organism, a chemical exposure, a genetic defect, or a deficiency condition. a form of individual or social behavior, such as reckless driving or risky sexual behavior, may lead to injury or disease. the host may be immune or susceptible as a result of many contributing social and environmental factors. the environment includes the vector, which may be a malaria-bearing mosquito, a contaminated needle shared by drug users, lead-contaminated paint, or an abusive family situation. assuming a natural state of "wellness" -i.e., optimal health or a sense of well-being, function, and absence of disease -a disease process may begin with the onset of a disease, infectious or non-infectious, following a somewhat characteristic pattern of "incubation" described by clinicians and epidemiologists. preclinical or predisposing events may be detected by a clinical history, with determination of risk including possible exposure or presence of other risk factors. interventions, before and during the process, are intended to affect the later course of the disease. the clinical course of a disease, or its laboratory or radiological findings, may be altered by medical or public health intervention, leading to the resolution or continuation of the disease with fewer or less severe secondary sequelae. thus, the intervention becomes part of the natural history of the disease. the natural history of an infectious disease in a population will be affected by the extent of prior vaccination or previous exposure in the community. diseases particular to children are often so because the adult population is immune from previous exposure or vaccinations. measles and diphtheria, primarily childhood diseases, now affect adults to a large extent because they are less protected by naturally acquired immunity or are vulnerable when their immunity wanes naturally or as a result of inadequate vaccination in childhood. in chronic disease management, high costs to the patient and the health system accrue where preventive services or management are inadequate, not yet available, or inaccessible or where there is a failure to apply the necessary interventions. the progress of diabetes to severe complications such as cardiovascular, renal, and ocular disease is delayed or reduced by good management of the condition, with a combination of smoking cessation, diet, exercise, and medications with good medical supervision. the patient with advanced chronic obstructive pulmonary disease or congestive heart failure may be managed well and remain stable with smoking avoidance, careful management of medications, immunizations against influenza and pneumonia, and other prevention-oriented care needs. where these are not applied or if they fail, the patient may require long and expensive medical and hospital care. failure to provide adequate supportive care will show up in ways that are more costly to the health system and will prove more life-threatening to the patient. the goal is to avoid where possible the necessity for tertiary care, substituting tertiary prevention, i.e., supportive rehabilitation to maximum personal function and maintaining a stable functional status. as in an individual, the phenomenon of a disease in a population may follow a course in which many factors interplay, and where interventions affect the natural course of the disease. the epidemiological patterns of an infectious disease can be assessed in their occurrence in the population or their mortality rates, just as they can for individual cases. the classic mid-nineteenth-century description of measles in the faroe islands by panum showed the transmission and the epidemic nature of the disease as well as the protective effect of acquired immunity (see chapter ). similar, more recent breakthroughs in medical, epidemiological, biological, and social sciences have produced enormous benefit for humankind as discussed throughout this text, with some examples. these include the eradication of smallpox and in the coming years, poliomyelitis, measles, leprosy, and other dreaded diseases known for millennia; the near-elimination of rheumatic heart disease and peptic ulcers in the industrialized countries; vast reduction in mortality from stroke and coronary heart disease (chd); and vaccines (against hepatitis b and hpv) for the prevention of cancers. these and other great achievements of the twentieth and early part of the twenty-first centuries hold great promise for humankind in the coming decades, but great challenges lie ahead as well. the biggest challenge is to bring the benefits of known public health capacity to the poorest population of each country and the poorest populations globally. in developed countries a major challenge is to renew efforts of public health capacity to bear on prevention of chronic conditions such as diabetes and obesity, considered to be at pandemic proportions; and the individual and societal effects of mental diseases. in public health today, fears of a pandemic of avian influenza are based on transmission of avian or other animal-borne (zoonotic) prions or viruses to humans and then their adaptation permitting human-to-human spread. with large numbers of people living in close contact with many animals (wild and domestic fowl), such as in china and south-east asia, and rapid transportation around the world, the potential for global spread of disease is almost without historical precedent. indeed, many human infectious diseases are zoonotic in origin and transferred from natural wildlife reservoirs to humans either directly or via domestic or other wild animals, such as from birds to chickens to humans in avian influenza. monitoring or immunization of domestic animals requires a combination of multidisciplinary zoonotic disease management strategies, public education and awareness, and veterinary public health monitoring and control. rift valley fever, equine encephalitis, and more recently sars and avian influenza associated with bird-borne viral disease which can affect humans, each show the terrible dangers of pandemic diseases. ebola virus is probably sustained between outbreaks among fruit bats, or as recently suggested wild or domestic pigs, and may become a major threat to public health as human case fatality rates decline, meaning that patients and carriers, or genetic drift of the virus with possible airborne transmission, may spread this deadly disease more widely than in the past (see chapter ). the health of populations, like the health of individuals, depends on societal factors no less than on genetics, personal risk factors, and medical services. social inequalities in health have been understood and documented in public health over the centuries. the chadwick and shattuck reports of - documented the relationship of poverty and bad sanitation, housing, and working conditions with high mortality, and ushered in the idea of social epidemiology. political and social ideologies thought that the welfare state, including universal health care systems of one type or another, would eliminate social and geographic differences in health status and this is in large part true. from the introduction of compulsory health insurance in germany in the s to the failed attempt in the usa at national health insurance in (see chapters , and ) and the more recent achievements of us president obama in - , social reforms to deal with inequalities in health have focused on improving access to medical and hospital care. almost all industrialized countries have developed such systems, and the contribution of these programs to improve health status has been an important part of social progress, especially since world war ii. but even in societies with universal access to health care, people of lower socioeconomic status (ses) suffer higher rates of morbidity and mortality from a wide variety of diseases. the black report (douglas black) in the uk in the early s pointed out that the class v population (unskilled laborers) had twice the total and specific mortality rates of the class i population (professional and business) for virtually all disease categories, ranging from infant mortality to death from cancer. the report was shocking because all britons have had access to the comprehensive national health service (nhs) since its inception in , with access to a complete range of services at no cost at time of service, close relations to their general practitioners, and good access to specialty services. these findings initiated reappraisals of the social factors that had previously been regarded as the academic interests of medical sociologists and anthropologists and marginal to medical care. more recent studies and reviews of regional, ethnic, and socioeconomic differentials in patterns of health care access, morbidity, and mortality indicate that health inequities are present in all societies including the uk, the usa, and others, even with universal health insurance or services. the ottawa charter on health promotion in placed a new paradigm before the world health community that recognized social and political factors as no less important ion health that traditional medical and sanitary public health measures. these concepts helped the world health community to cope with new problems such as hiv/aidsfor which there was neither a medical cure nor a vaccine to prevent the disease. its control came to depend in the initial decades almost entirely on education and change in lifestyles, until the advent of the antiretroviral drugs in the s. there is still no viable vaccine. although the epidemiology of cardiovascular disease shows the direct relationship of the now classic risk factors of stress, smoking, poor diet, and physical inactivity, differences in mortality from cardiovascular disease between different classes among british civil servants are not entirely explainable by these factors. the differences are also affected by social and economic issues that may relate to the psychological needs of the individual, such as the degree of control people have over their own lives. blue-collar workers have less control over their lives, their working life in particular, than their white-collar counterparts, and have higher rates of chd mortality than higher social classes. other work shows the effects of migration, unemployment, drastic social and political change, and binge drinking, along with protective effects of healthy lifestyle, religiosity, and family support systems in cardiovascular diseases. social conditions affect disease distribution in all societies. in the usa and western europe, tb has re-emerged as a significant public health problem in urban areas partly because of high-risk population groups, owing to poverty and alienation from society, as in the cases of homelessness, drug abuse, and hiv infection. in countries of eastern europe and the former soviet union, the recent rise in tb incidence has resulted from various social and economic factors in the early s, including the large-scale release of prisoners. in both cases, diagnosis and prescription of medication are inadequate, and the community at large becomes at risk because of the development of antibioticresistant strains of tubercle bacillus readily spread by inadequately treated carriers, acting as human vectors. studies of ses and health are applicable and valuable in many settings. in alameda county, california, differences in mortality between black and white population groups in terms of survival from cancer became insignificant when controlled for social class. a -year follow-up study of the county population reported that low-income families in california are more likely than those on a higher income to have physical and mental problems that interfere with daily life, contributing to further impoverishment. studies of the association between indicators of ses and recent screening in the usa, australia, finland, and elsewhere showed that lower ses women use less preventive care such as papanicolaou (pap) smears for cervical cancer than women of higher ses, despite having greater risk for cervical cancer. many factors in ses inequalities are involved, including transportation and access to primary care, differences in health insurance coverage, educational levels, poverty, high-risk behaviors, social and emotional distress, feeling a lack of control over one's own life, employment, occupation, and inadequate family or community social support systems. many barriers exist owing to difficulties in access and the lack of availability of free or low-cost medical care, and the absence or limitations of health insurance is a further factor in the socioeconomic gradient. the recognition that health and disease are influenced by many factors, including social inequalities, plays a fundamental role in the new public health paradigm. health care systems need to take into account economic, social, physical, and psychological factors that otherwise will limit the effectiveness of even the best medical care. the health system includes access to competent and responsible primary care as well as by the wider health system, including health promotion, specific prevention and population-based health protection. the paradigm of the host-agent-environment triad (figures . and . ) is profoundly affected by the wider context. the sociopolitical environment and organized efforts at intervention affect the epidemiological and clinical course of disease of the individual. medical care is essential, as is public health, but the persistent health inequities seen in most regions and countries require societal attention. success or failure in improving the conditions of life for the poor, and other vulnerable "risk groups", affect national or regional health status and health system performance. the health system is meant to reduce the occurrence or bad outcome of disease, either directly by primary prevention or treatment as secondary prevention or by maximum rehabilitation as tertiary prevention, or equally important indirectly by reducing community or individual risk factors. the the effects of social conditions on health can be partly offset by interventions intended to promote healthful conditions; for example, improved sanitation, or through good-quality primary and secondary health services, used efficiently and effectively made available to all. the approaches to preventing disease or its complications may require physical changes in the environment, such as removal of the broad street pump handle to stop the cholera epidemic in london, or altering diets as in goldberger's work on pellagra. some of the great successes of public health have been and continue to be low technology. examples, among many others, include insecticide-impregnated bednets and other vector control measures, oral rehydration solutions, treatment and cure of peptic ulcers, exercise and diet to reduce obesity, hand washing in hospitals (and other health facilities), community health workers, and condoms and circumcision for the prevention of stis, including hiv and cancer of the cervix. the societal context in terms of employment, social security, female education, recreation, family income, cost of living, housing, and homelessness is relevant to the health status of a population. income distribution in a wealthy country may leave a wide gap between the upper and lower socioeconomic groups, which affects health status. the media have great power to sway public perception of health issues by choosing what to publish and the context in which to present information to society. modern media may influence an individual's tendency to overestimate the risk of some health issues while underestimating the risk of others, ultimately influencing health choices, such as occurred with public concern regarding false claims of an association between the measles-mumps-rubella (mmr) vaccine and autism in the uk (see the wakefield effect, chapter ). the new public health has an intrinsic responsibility for advocacy of improved societal conditions in its mission to promote optimal community health. an ultimate goal of public health is to improve health and to prevent widespread disease occurrence in the population and in an individual. the methods of achieving this are wide and varied. when an objective has been defined in "social justice is a matter of life and death. it affects the way people live, their consequent chance of illness, and their risk of premature death. we watch in wonder as life expectancy and good health continue to increase in parts of the world and in alarm as they fail to improve in others. a girl born today can expect to live for more than years if she is born in some countries -but less than years if she is born in others. within countries there are dramatic differences in health that are closely linked with degrees of social disadvantage. differences of this magnitude, within and between countries, simply should never happen. these inequities in health, avoidable health inequalities arise because of the circumstances in which people grow, live, work, and age, and the systems put in place to deal with illness. the conditions in which people live and die are, in turn, shaped by political, social, and economic forces. social and economic policies have a determining impact on whether a child can grow and develop to its full potential and live a flourishing life, or whether its life will be blighted. increasingly the nature of the health problems rich and poor countries have to solve are converging. the development of a society, rich or poor, can be judged by the quality of its population's health, how fairly health is distributed across the social spectrum, and the degree of protection provided from disadvantage as a result of ill-health." preventing disease, the next step is to identify suitable and feasible methods of achieving it, or a strategy with tactical objectives. this determines the method of operation, course of action, and resources needed to carry it out. the methods of public health are categorized as health promotion, and primary, secondary, and tertiary prevention (box . ). health promotion is the process of enabling people and communities to increase control over factors that influence their health, and thereby to improve their health (adapted from the ottawa charter of health promotion, ; box . ). health promotion is a guiding concept involving activities intended to enhance individual and community health and well-being (box . ). it seeks to increase involvement and control by the individual and the community in their own health. it acts to improve health and social welfare, and to reduce specific determinants of diseases and risk factors that adversely affect the health, well-being, and productive capacities of an individual or society, setting targets based on the size of the problem but also the feasibility of successful intervention, in a cost-effective way. this can be through direct contact with the patient or risk group, or act indirectly through changes in the environment, legislation, or public policy. control of aids relies on an array of interventions that promote change in sexual behavior and other contributory risks such as sharing of needles among drug users, screening of blood supply, safe hygienic practices in health care settings, and education of groups at risk such as teenagers, sex workers, migrant workers, and many others. control of aids is also a clinical problem in that patients need antiretroviral therapy (art), but this becomes a management and policy issue for making these drugs available and at an affordable price for the poor countries most affected. this is an example of the challenge and effectiveness of health promotion and the new public health. health promotion is a key element of the new public health and is applicable in the community, the clinic or hospital, and in all other service settings. some health promotion activities are government legislative and box . modes of prevention l health promotion -fostering national, community, and individual knowledge, attitudes, practices, policies, and standards conducive to good health; promoting legislative, social, or environmental conditions; promoting knowledge and practices for self-care that reduce individual and community risk; and creating a healthful environment. it is directed toward action on the determinants of health. l health protection -activities of official health departments or other agencies empowered to supervise and regulate food hygiene, community and recreational water safety, environmental sanitation, occupational health, drug safety, road safety, emergency preparedness, and many other activities to eliminate or reduce as much as possible risks of adverse consequences to health. l primary prevention -preventing a disease from occurring, e.g., vaccination to prevent infectious diseases, advice to stop smoking to prevent lung cancer. l secondary prevention -making an early diagnosis and giving prompt and effective treatment to stop progress or shorten the duration and prevent complications from an already existing disease process, e.g., screening for hypertension or cancer of cervix and colorectal cancer for early case finding, early care and better outcomes. l tertiary prevention -stopping progress of an already occurring disease, and preventing complications, e.g., in managing diabetes and hypertension to prevent complications; restoring and maintaining optimal function once the disease process has stabilized, e.g., promoting functional rehabilitation after stroke and myocardial infarction with long-term follow-up care. health promotion (hp) is the process of enabling people to increase control over, and to improve their health. hp represents a comprehensive social and political process, and not only embraces actions directed at strengthening the skills and capabilities of individuals. hp also undertakes action directed towards changing social, environmental, and economic conditions so as to alleviate their impact on public and individual health. health promotion is the process of enabling people to increase control over the determinants of health and thereby improve their health. participation is essential to sustain health promotion action. the ottawa charter identifies three basic strategies for health promotion. these are advocacy for health to create the essential conditions for health indicated above; enabling all people to achieve their full health potential; and mediating between the different interests in society in the pursuit of health. these strategies are supported by five priority action areas as outlined in the ottawa charter for health promotion: regulatory interventions such as mandating the use of seat belts in cars, requiring that children be immunized to attend school, declaring that certain basic foods must have essential minerals and vitamins added to prevent nutritional deficiency disorders in vulnerable population groups, and mandating that all newborns should be given prophylactic vitamin k to prevent hemorrhagic disease of the newborn. setting food and drug standards and raising taxes on cigarettes and alcohol to reduce their consumption are also part of health promotion. promoting a healthy lifestyle is a major known obesity-preventive activity. health promotion is provided by organizations and people with varied professional backgrounds working towards common goals of improvement in the health and quality of individual and community life. initiatives may come from government with dedicated allocation of funds to address specific health issues, from donors, or from advocacy or community groups or individuals to promote a specific or general cause in health. raising awareness to inform and motivate people about their own health and lifestyle factors that might put them at risk requires teaching young people about the dangers of sexually transmitted diseases, smoking, and alcohol abuse to reduce risks associated with their social behavior. it might include disseminating information on healthy nutrition; for example, the need for folic acid supplements for women of childbearing age and multiple vitamins for elderly, as well as the elements of a healthy diet, compliance with immunization recommendations, compliance with screening programs, and many others. community and peer group attitudes and standards affect individual behavior. health promotion endeavors to create a climate of knowledge, attitudes, beliefs, and practices that are associated with better health outcomes. international conferences following on from the ottawa charter were held in adelaide in , sundsvall in , jakarta in , mexico in , bangkok in , and nairobi in . the principles of health promotion have been reiterated and have influenced public policy regarding public health as well as the private sector. health promotion has a track record of proven success in numerous public health issues where a biomedical solution was not available. the hiv/aids pandemic from the s until the late s had no medical treatment and control measures relied on screening, education, lifestyle changes, and supportive care. health promotion brought forward multiple interventions, from condom use and distribution, to needle exchanges for intravenous drug users, to male circumcision in high-prevalence african countries. medical treatment was severely limited until art was developed. the success of art also depends on a strong element of health promotion in widening the access to treatment and the success of medications to reduce transmission, most remarkably in reducing maternal-fetal transmission (see chapter ). similarly, in the battle against cardiovascular diseases, health promotion was an instrumental factor in raising public awareness of the importance of management of hypertension and smoking reduction, dietary restraint, and physical exercise. the success of massive reductions in stroke and chd mortality is as much the result of health promotion as of improved medical care (see chapter ). the character of public health carries with it a "good cop, bad cop" dichotomy. the "good cop" is persuasive and educational trying to convince people to do the right thing in looking after their own health: diet, exercise, smoking cessation, and others. on the other side, the "bad cop" role is regulatory and punitive. public health has a serious responsibility and role in the enforcement of laws and regulation to protect the public health. some of these are restrictive box . elements of health promotion . address the population as a whole in health-related issues, in everyday life as well as people at risk for specific diseases. . direct action to risk factors or causes of illness or death. . undertake activist approach to seek out and remedy risk factors in the community that adversely affect health. . promote factors that contribute to a better condition of health of the population. . initiate actions against health hazards, including communication, education, legislation, fiscal measures, organizational change, community development, and spontaneous local activities. . involve public participation in defining problems and deciding on action. . advocate relevant environmental, health, and social policy. . encourage health professional participation in health education and health advocacy. . advocate for health based on human rights and solidarity. . invest in sustainable policies, actions, and infrastructure to address the determinants of health. . build capacity for policy development, leadership, health promotion practice, knowledge transfer and research, and health literacy. . regulate and legislate to ensure a high level of protection from harm and enable equal opportunity for health and well-being for all people. . partner and build alliances with public, private, nongovernmental, and international organizations and civil society to create sustainable actions. . make the promotion of health central to the global development agenda. of individual rights that may damage other people or are requirements based on strong evidence of benefits to population health. readily accepted are food and drug standards, such as pasteurization of milk, and iodization of salt; requirements to drive on the right-hand side of the road (except in some countries such as the uk), to wear seat belts and for motorcyclists to wear safety helmets; and not smoking in public places. enforcement of these and similar statutory or regulatory requirements is vital in a civil society to protect the public from health hazards and to protect people from harm and exploitation by unscrupulous manufacturers and marketing. cigarette advertising and sponsorship of sports events by tobacco companies are banned in most upper income countries. the use of transfats in food manufacturing and baking is now banned and salt reduction is being promoted and even mandated in many us local authorities to reduce cardiovascular disease. advertising of unhealthy snack foods on children's television programs and during child-watching hours is commonly restricted. banning high-sugar soda drink distribution in schools is a successful intervention to reduce the current child obesity epidemic. melamine use in milk powders and baby formulas, which caused widespread illness and death of infants in china, is now banned and a punishable offence for manufacture or distribution in china and worldwide. examples of this aspect of public health are mentioned throughout this text, especially in chapters and on nutrition, and environmental and occupational health, respectively. the regulatory enforcement function of public health is sometimes controversial and portrayed as interference with individual liberty. fluoridation of community water supplies is an example where aggressive lobby groups opposing this safe and effective public health measure are still common. this is discussed in chapter . equally important is the public health policy issue of resource allocation and taxation for health purposes. taxation is an unpopular measure that governments must employ and enforce in order to do the public's business. the debate over the patient protection and affordable care act (ppaca or "obamacare"), discussed elsewhere in this and other chapters, shows how bitter the arguments can become, yet the goal of equality of access to health care cannot be denied as a public good, demonstrably contributing to the health of the nation. primary prevention refers to those activities that are undertaken to prevent disease or injury from occurring at all. primary prevention works with both the individual and the community. it may be directed at the host to increase resistance to the agent (such as in immunization or cessation of smoking), or at environmental activities to reduce conditions favorable to the vector for a biological agent, such as mosquito vectors of malaria or dengue fever. landmark examples include the treatment and prevention of scurvy among sailors based on james lind's findings in a classic clinical epidemiological study in , and john snow's removal of the handle from the broad street pump to stop a cholera epidemic in london in (see chapter ). primary prevention includes elements of health protection such as ensuring water, food and drug, and workplace safety; chlorination of drinking water to prevent transmission of waterborne enteric diseases; pasteurization of milk to prevent gastrointestinal diseases; mandating wearing seat belts in motor vehicles to prevent serious injury and death in road crashes; and reducing the availability of firearms to reduce injury and death from intentional, accidental, or random violence. it also includes direct measures to prevent diseases, such as immunization to prevent polio, tetanus, pertussis, and diphtheria. health promotion and health protection blend together as a group of activities that reduce risk factors and diseases through many forms of intervention such as changing smoking legislation or preventing birth defects by fortification of flour with folic acid. prevention of hiv transmission by needle exchange for intravenous drug users, promoting condom usage, and promoting male circumcision in africa, and the distribution of condoms and clean needles for hivpositive drug users are recent examples of primary prevention associated with health promotion programs. primary prevention also includes activities within the health system that can lead to better health. this may mean, for example, setting standards and to reduce hospital infections, and ensuring that doctors not only are informed of appropriate immunization practices and modern prenatal care or screening programs for cancer of the cervix, colon, and breast, but also are aware of their vital role in preventing cardiovascular and other non-communicable diseases. in this role, the health care provider serves as a teacher and guide, as well as a diagnostician and therapist. like health promotion, primary prevention does not depend on health care providers alone; health promotion works to increase individual and community consciousness of self-care, mainly by raising awareness and information levels and empowering the individual and the community to improve self-care, to reduce risk factors, and to live healthier lifestyles. secondary prevention is early diagnosis and management to prevent complications from a disease. public health interventions to prevent the spread of disease include the identification of sources of the disease and the implementation of steps to stop it, as shown in snow's closure of the broad street pump. secondary prevention includes steps to isolate cases and treat or immunize contacts so as to prevent further cases of meningitis or measles, for example, in outbreaks. for current epidemics such as hiv/aids, primary prevention is largely based on education, abstinence from any and certainly risky sexual behavior, circumcision, and treatment of patients in order to improve their health and to reduce the risk of spread of hiv. for high-risk groups such as intravenous drug users, needleexchange programs reduce the risk of spread of hiv, and hepatitis b and c. distribution of condoms to teenagers, military personnel, truck drivers, and commercial sex workers helps to prevent the spread of stis and aids in schools and colleges, as well as among the military. the promotion of circumcision is shown to be effective in reducing the transmission of hiv and of hpv (the causative organism for cancer of the cervix). all health care providers have a role in secondary prevention; for example, in preventing strokes by early identification and adequate care of hypertension. the child who has an untreated streptococcal infection of the throat may develop complications which are serious and potentially life-threatening, including rheumatic fever, rheumatic valvular heart disease, and glomerulonephritis. a patient found to have elevated blood pressure should be advised about continuing management by appropriate diet and weight loss if obese, regular physical exercise, and long-term medication with regular follow-up by a health provider in order to reduce the risk of stroke and other complications. in the case of injury, competent emergency care, safe transportation, and good trauma care may reduce the chance of death and/or permanent handicap. screening and high-quality care in the community prevent complications of diabetes, including heart, kidney, eye, and peripheral vascular disease. they can also prevent hospitalizations, amputations, and strokes, thus lengthening and improving the quality of life. health care systems need to be actively engaged in secondary prevention, not only as individual doctors' services, but also as organized systems of care. public health also has a strong interest in promoting highquality care in secondary and tertiary care hospital centers in such areas of treatment as acute myocardial infarction, stroke, and injury in order to prevent irreversible damage. measures include quality of care reviews to promote adequate longterm postmyocardial infarction care with aspirin and betablockers or other medication to prevent or delay recurrence and second or third myocardial infarctions. the role of highquality transportation and care in emergency facilities of hospitals in public health is vital to prevent long-term damage and disability; thus, cardiac care systems including publicly available defibrillators, catheterization, the use of stents, and bypass procedures are important elements of health care policy and resource allocation, which should be accessible not only in capital cities but also to regional populations. tertiary prevention involves activities directed at the host or patient, but also at the social and physical environment in order to promote rehabilitation, restoration, and maintenance of maximum function after the disease and its complications have stabilized. the person who has undergone a cerebrovascular accident or trauma will reach a stage where active rehabilitation can help to restore lost functions and prevent recurrence or further complications. the public health system has a direct role in the promotion of disability-friendly legislation and standards of building, housing, and support services for chronically ill, handicapped, and elderly people. this role also involves working with many governmental social and educational departments, but also with advocacy groups, ngos, and families. it may also include the promotion of disability-friendly workplaces and social service centers. treatment for conditions such as myocardial infarction or a fractured hip now includes early rehabilitation in order to promote early and maximum recovery with restoration to optimal function. the provision of a wheelchair, walkers, modifications to the home such as special toilet facilities, doors, and ramps, along with transportation services for paraplegics are often the most vital factors in rehabilitation. public health agencies work with groups in the community concerned with promoting help for specific categories of risk group, disease, or disability to reduce discrimination. community action is often needed to eliminate financial, physical, or social barriers, promote community awareness, and finance special equipment or other needs of these groups. close follow-up and management of chronic disease, physical and mental, require home care and ensuring an appropriate medical regimen including drugs, diet, exercise, and support services. the follow-up of chronically ill people to supervise the taking of medications, monitor changes, and support them in maximizing their independent capacity in activities of daily living is an essential element of the new public health. public health uses a population approach to achieve many of its objectives. this requires defining the population, including trends of change in the age and gender distribution of the population, fertility and birth rates, spread of disease and disability, mortality, marriage and migration, and socioeconomic factors. the reduction of infectious disease as the major cause of mortality, increased longevity coupled with declining fertility rates, resulted in changes in the age composition, or a demographic transition. demographic changes, such as fertility and mortality patterns, are important factors in changing the age distribution of the population, resulting in a greater proportion of people surviving to older ages. declining infant mortality, increasing educational levels of women, the availability of birth control, and other social and economic factors lead to changes in fertility patterns and the demographic transition -an aging of the population -with important effects on health service needs. the age and gender distribution of a population affects and is affected by patterns of disease. change in epidemiological patterns, or an epidemiological shift, is a change in predominant patterns of morbidity and mortality. the transition of infectious diseases becoming less prominent as causes of morbidity and mortality and being replaced by chronic and non-infectious diseases has occurred in both developed and developing countries. the decline in mortality from chronic diseases, such as cardiovascular disease, represents a new stage of epidemiological transition, creating an aging population with higher standards of health but also long-term community support and care needs. monitoring and responding to these changes are fundamental responsibilities of public health, and a readiness to react to new, local, or generalized changes in epidemiological patterns is vital to the new public health. societies are not totally homogeneous in ethnic composition, levels of affluence, or other social markers. on one hand, a society classified as developing may have substantial numbers of people with incomes that promote overnutrition and obesity, so that disease patterns may include increasing prevalence of diseases of excesses, such as diabetes. on the other hand, affluent societies include population groups with disease patterns of poverty, including poor nutrition and low birth-weight babies. a further stage of epidemiological transition has been occurring in the industrialized countries since the s, with dramatic reductions in mortality from chd, stroke and, to a lesser extent, trauma. the interpretation of this epidemiological transition is still not perfectly clear. how it occurred in the industrialized western countries but not in those of the former soviet union is a question whose answer is vital to the future of health in russia and some countries of eastern europe. developing countries must also prepare to cope with increasing epidemics of non-infectious diseases, and all countries face renewed challenges from infectious diseases with antibiotic resistance or newly appearing infectious agents posing major public health threats. demographic change in a country may reflect social and political decisions and health system priorities from decades before. russia's rapid population decline since the s, china's gender imbalance with a shortage of millions of young women, egypt's rapid population growth outstripping economic capacity, and many other examples indicate the severity and societal importance of capacity to analyze and formulate public health and social policies to address such fundamental sociopolitical issues. aging of the population is now the norm in most developed countries as a result of low birth and declining mortality rates. this change in the age distribution of a population has many associated social and economic issues as to the future of social welfare with a declining age cohort to provide the workforce. the aging population requires pension and health care support which make demands of social security systems that will depend on economic growth with a declining workforce. in times of economic stress, as in europe, this situation is made more difficult by longstanding short working weeks, early pension ages, and high social benefits. however, this results in unemployment among young people in particular and social conflict. the interaction of increasing life expectancy and a declining workforce is a fundamental problem in the high-income countries. this imbalance may be resolved in part through productivity gains and switching of primary production to countries with large still underutilized workforces, while employment in the developed countries will depend on service industries including health and the economic growth generated by higher technology and intellectual property and service industries. the challenge of keeping populations and individuals healthy is reflected in modern health services. each component of a health service may have developed with different historical emphases, operating independently as a separate service under different administrative auspices and funding systems, competing for limited health care resources. in this situation, preventive community care receives less attention and resources than more costly treatment services. figure . suggests a set of health services in an interactive relationship to serve a community or defined population, but the emphasis should be on the interdependence of these services with one other and with the comprehensive network in order to achieve effective use of resources and a balanced set of services for the patient, the client or patient population, and the community. clinical medicine and public health each play major roles in primary, secondary, and tertiary prevention. each may function separately in their roles in the community, but optimal success lies in their integrated efforts. allocation of resources should promote management and planning practices to assist this integration. there is a functional interdependence of all elements of health care serving a definable population. the patient should be the central figure in the continuum or complex of services available. effectiveness in use of resources means that providing the service most appropriate for meeting the individual's or group's needs at a point in time are those that should be applied. this is the central concept in currently developing innovations in health care delivery in the usa with organizations using terms such as patient centered medical home, accountable care organizations (acos), and population health management systems, which are being promoted in the obamacare health reforms now in process (see chapter ) (shortell et al., ) . separate organization and financing of services place barriers to appropriate provision of services for both the community and the individual patient. the interdependence of services is a challenge in health care organizations for the future. where there is competition for limited resources, pressures for tertiary services often receive priority over programs to prevent children from dying of preventable diseases. public health must be seen in the context of all health care and must play an influential role in promoting prevention at all levels. clinical services need public health in order to provide prevention and community health services that reduce the burden of disease, disability, and dependence on the institutional setting. health was traditionally thought of as a state of absence of disease, pain, or disability, but has gradually been expanded to include physical, mental, and societal well-being. in , c. e. a. winslow, professor of public health at yale university, defined public health as follows: "public health is the science and art of ( ) preventing disease, ( ) prolonging life, and ( ) winslow's far-reaching definition remains a valid framework but is unfulfilled when clinical medicine and public health have financing and management barriers between them. in many countries, isolation from the financing and provision of medical and nursing care services left public health with the task of meeting the health needs of the indigent and underserved population groups with inadequate resources and recognition. health insurance organizations for medical and hospital care have in recent years been more open to incorporating evidence-based preventive care, but the organization of public health has lacked the same level of attention. in some countries, the limitations have been conceptual in that public health was defined primarily in terms of control of infectious, environmental, and occupational diseases. a more recent and widely used definition is: "public health is the science and art of preventing disease, prolonging life, and promoting health through the organized efforts of society." this definition, coined in in the public health in england report by sir donald acheson, reflects the broad focus of modern public health. terms such as social hygiene, preventive medicine, community medicine, and social medicine have been used to denote public health practice over the past century. preventive medicine is the application of preventive measures by clinical practitioners combining some elements of public health with clinical practice relating to individual patients. preventive medicine defines medical or clinical personal preventive care, with stress on risk groups in the community and national efforts for health promotion. the focus is on the health of defined populations to promote health and well-being using evidence-based guidelines for cost-effective preventive measures. measures emphasized include screening and follow-up of chronic illnesses, and immunization programs; for example, influenza and pneumococcal pneumonia vaccines are used by people who are vulnerable because of their age, chronic diseases, or risk of exposure, such as medical and nursing personnel and those providing other personal clinical services. clinical medicine also deals in the area of prevention in the management of patients with hypertension or diabetes, and in doing so prevents the serious complications of these diseases. social medicine is also primarily a medical specialty which looks at illness in an individual in the family and social context, but lacks the environmental and regulatory and organized health promotion functions of public health. community health implies a local form of health intervention, whereas public health more clearly implies a global approach, which includes action at the international, national, state, and local levels. some issues in health can be dealt with at the individual, family, or community level; others require global strategies and intervention programs with regional, national, or international collaboration and leadership. the social medicine movement originated to address the harsh conditions of the working population during the industrial revolution in mid-nineteenth-century europe. an eminent pioneer in cellular pathology, rudolph virchow provided leadership in social medicine powered by the revolutionary movements of , and subsequent social democrat political movements. their concern focused on harsh living and health conditions among the urban poor working class and neglectful political norms of the time. social medicine also developed as an academic discipline and advocacy orientation by providing statistical evidence showing, as in various governmental reports in the mid-nineteenth century, that poverty among the working class was associated with short life expectancy and that social conditions were key factors in the health of populations and individuals. this movement provided the basis for departments in medical faculties and public health education throughout the world stressing the close relationship between political priorities and health status. this continued in the twentieth century and in the usa found expression in pioneering work since the s at montefiore hospital in new york and with victor sidel, founding leader of the community health center movement the usa from the s. in the twenty-first century this movement continues to emphasize relationships between politics, society, disease, and medicine, and forms of medical practice derived from it, as enunciated by prominent advocates such as harvardbased paul farmer in haiti, russia and rwanda, and in the uk by martin mckee and others (nolte and mckee, ) . similar concepts are current in the usa under headings such as family medicine, preventive medicine, and social medicine. this movement has also influenced sir michael marmot and others in the world health commission of health inequalities of , with a strong influence on the un initiative to promote mdgs, whose first objective is poverty reduction (commission on inequalities report ). application of the idea of poverty reduction as a method of reducing health inequalities has been successful recently in a large field trial in brazil showing greater reduction in child mortality where cash bonuses were awarded by municipalities for the poor families than that observed in other similar communities (rasella, ). in the usa, this movement is supported by increased health insurance coverage for the working poor, with funding for preventive care and incentives for community health centers in the obamacare plan of for implementation in the coming years to provide care for uninsured and underserved populations, particularly in urban and rural poverty areas. the political aspect of social medicine is the formulation of and support for national initiatives to widen health care coverage to the percent of the us population who are still uninsured, and to protect those who are arbitrarily excluded owing to previous illnesses, caps on coverage allowed, and other exploitative measures taken by private insurance that frequently deny americans access to the high levels of health care available in the country. the ethical base of public health in europe evolved in the context of its successes in the nineteenth and early twentieth centuries along with ideas of social progress. but the twentieth century was also replete with extremism and wide-scale abuse of human rights, with mass executions, deportations, and starvation as official policy in fascist and stalinist regimes. eugenics, a pseudoscience popularized in the early decades of the twentieth century, promoted social policies meant to improve the hereditary qualities of a race by methods such as sterilization of mentally handicapped people. the "social and racial hygiene" of the eugenics movements led to the medicalization of sterilization in the usa and other countries. this was adopted and extended in nazi germany to a policy of murder, first of the mentally and physically handicapped and then of "racial inferiors". these eugenics theories were widely accepted in the medical community in germany, then used by the nazi regime to justify medically supervised killing of hundreds of thousands of helpless, incapacitated individuals. this practice was linked to wider genocide and the holocaust, with the brutalization and industrialized murder of over million jews and million other people, and corrupt medical experimentation on prisoners. following world war ii, the ethics of medical experimentation (and public health) were codified in the nuremberg code and universal declaration of human rights based on lessons learned from these and other atrocities inflicted on civilian populations (see chapter ). threats of genocide, ethnic cleansing, and terrorism are still present on the world stage, often justified by current warped versions of racial hygienic theories. genocidal incitement and actual genocide and terrorism have recurred in the last decades of the twentieth century and into the twenty-first century in the former yugoslav republics, africa (rwanda and darfur), south asia, and elsewhere. terrorism against civilians has become a worldwide phenomenon with threats of biological and chemical agents, and potentially with nuclear capacity. asymmetrical warfare of insurgencies which use innocent civilians for cover, as with other forms of warfare, carries with it grave dangers to public health, human rights, and international stability, as seen in the twenty-first century in south sudan, darfur, dr congo, chechnya, iraq, afghanistan, and pakistan. in , kerr white and colleagues defined medical ecology as population-based research providing the foundation for management of health care quality. this concept stresses a population approach, including those not attending and those using health services. this concept was based on previous work on quality of care, randomized clinical trials, medical audit, and structure-process-outcome research. it also addressed health care quality and management. these themes influenced medical research by stressing the population from which clinical cases emerge as well as public health research with clinical outcome measures, themes that recur in the development of health services research and, later, evidence-based medicine. this led to the development of the agency for health care policy and research and development in the us department of health and human services and evidence-based practice centers to synthesize fundamental knowledge for the development of information for decision-making tools such as clinical guidelines, algorithms, or pathways. clinical guidelines and recommended best practices have become part of the new public health to promote quality of patient care and public health programming. these can include recommended standards; for example, follow-up care of the postmyocardial infarction patient, an internationally recommended immunization schedule, recommended dietary intake or food fortification standards, and mandatory vitamin k and eye care for all newborns and many others (see chapter ). community-oriented primary care (copc) is an approach to primary health care that links community epidemiology and appropriate primary care, using proactive responses to the priority needs identified. copc, originally pioneered in south africa and israel by sidney and emily kark and colleagues in the s and s, stresses medical services in the community which need to be adapted to the needs of the population as defined by epidemiological analysis. copc involves community outreach and education, as well as clinical preventive and treatment services. copc focuses on community epidemiology and an active problem-solving approach. this differs from national or larger scale planning that sometimes loses sight of the local nature of health problems or risk factors. copc combines clinical and epidemiological skills, defines needed interventions, and promotes community involvement and access to health care. it is based on linkages between the different elements of a comprehensive basket of services along with attention to the social and physical environment. a multidisciplinary team and outreach services are important for the program, and community development is part of the process. in the usa, the copc concept has influenced health care planning for poor areas, especially provision of federally funded community health centers in attempts to provide health care for the underserved since the s. in more recent years, copc has gained wider acceptance in the usa, where it is associated with family physician training and community health planning based on the risk approach and "managed care" systems. indeed, the three approaches are mutually complementary (box . ). as the emphasis on health care reform in the late s moved towards managed care, the principles of copc were and will continue to be important in promoting health and primary prevention in all its modalities, as well as tertiary prevention with followup and maintenance of the health of the chronically ill. copc stresses that all aspects of health care have moved towards prevention based on measurable health issues in the community. through either formal or informal linkages between health services, the elements of copc are part of the daily work of health care providers and community services systems. the us institute of medicine issued the report on primary care in , defining primary care as "the provision of integrated, accessible health care services by clinicians who are accountable for addressing the majority of personal health care needs, developing a sustained partnership with patients and practicing in the context of the family and the community". this formulation was criticized by the american public health association (apha) as lacking a public health perspective and failing to take into account both the individual and the community health approaches. copc tries to bridge this gap between the perspectives of primary care and public health. the community, whether local, regional, or national, is the site of action for many public health interventions. moreover, understanding the characteristics of the community is vital to a successful community-oriented approach. by the s, new patterns of public health began to emerge, including all measures used to improve the health of the community, and at the same time working to protect and promote the health of the individual. the range of activities to achieve these general goals is very wide, including individual patient care systems and the community-wide activities that affect the health and well-being of the individual. these include the financing and management of health systems, evaluation of the health status of the population, and measures to improve the quality of health care. they place reliance on health promotion activities to change environmental risk factors for disease and death. they promote integrative and multisectoral approaches and the international health teamwork required for global progress in health. the definition of health in the charter of the who as a complete state of physical, mental, and social well-being had a ring of utopianism and irrelevance to states struggling to provide even minimal care in severely adverse political, economic, social, and environmental conditions (box . ). in , a more modest goal was set for attainment of a level of health compatible with maximum feasible social and economic productivity. one needs to recognize that health and disease are on a dynamic continuum that affects everyone. the mission for public health is to use a wide range of methods to prevent disease and premature death, and improve quality of life for the benefit of individuals and the community. the world health organization defines health as "a state of complete physical, mental and social well-being, not merely the absence of disease or infirmity" (who constitution, ) . in at the alma-ata conference on primary health care, the who related health to "social and economic productivity in setting as a target the attainment by all the people of the world of a level of health that will permit them to lead a socially and economically productive life". three general programs of work for the periods - , - , and - were formulated as the basis of national and international activity to promote health. in , the who, recognizing changing world conditions of demography, epidemiology, environment, and political and economic status, addressed the unmet needs of developing countries and health management needs in the industrialized countries, calling for international commitment to "attain targets that will make significant progress towards improving equity and ensuring sustainable health development". the object of the who is restated as "the attainment by all peoples of the highest possible level of health" as defined in the who constitution, by a wide range of functions in promoting technical cooperation, assisting governments, and providing technical assistance, international cooperation, and standards. in the s, most industrialized countries were concentrating energies and financing in health care on providing access to medical and hospital services through national insurance schemes. developing countries were often spending scarce resources trying to emulate this trend. the who was concentrating on categorical programs, such as eradication of smallpox and malaria, as well as the expanded program of immunization and similar specific efforts. at the same time, there was a growing concern that developing countries were placing too much emphasis and expenditure on curative services and not enough on prevention and primary care. the world health assembly (wha) in endorsed the primary care approach under the banner of "health for all by the year " (hfa ) . this was a landmark decision and has had important practical results. the who and the united nations children's fund (unicef) sponsored a seminal conference held in alma-ata, in the ussr ( kazakhstan), in , which was convened to refocus health policy on primary care. the alma-ata declaration stated that health is a basic human right, and that governments are responsible to assure that right for their citizens and to develop appropriate strategies to fulfill this promise. this proposition has come to be increasingly accepted in the international community. the conference stressed the right and duty of people to participate in the planning and implementation of their health care. it advocated the use of scientifically, socially, and economically sound technology. joint action through intersectoral cooperation was also emphasized. the alma-ata declaration focused on primary health care as the appropriate method of assuming adequate access to health care for all (box . ). many countries have gradually come to accept the notion of placing priority on primary care, resisting the temptation to spend high percentages of health care resources on high-tech and costly medicine. spreading these same resources into highly costeffective primary care, such as immunization and nutrition programs, provides greater benefit to individuals and to society as a whole. alma-ata provided a new sense of direction for health policy, applicable to developing countries and in a different way than the approaches of the developed countries. during the s, the health for all concept influenced national health policies in the developing countries with signs of progress in immunization coverage, for example, but the initiative was diluted as an unintended consequence by more categorical programs such as eradication of poliomyelitis. for example, developing countries have accepted immunization and diarrheal disease control as high-priority issues and achieved remarkable success in raising immunization coverage from some percent to over percent in just a decade. developed countries addressed these principles in different ways. in these countries, the concept of primary health care led directly to important conceptual developments in health. national health targets and guidelines are now common in many countries and are integral parts of box . declaration of alma-ata, : a summary of primary health care (phc) . reaffirms that health is a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity, and is a fundamental human right. existing gross inequalities in the health status of the people, particularly between developed and developing countries as well as within countries, are of common concern to all countries. . governments have a responsibility for the health of their people. the people have the right and duty to participate in planning and implementation of their health care. . a main social target is the attainment, by all peoples of the world by the year , of a level of health that will permit them to lead a socially and economically productive life. . phc is essential health care based on practical, scientifically sound, and socially acceptable methods and technology. . it is the first level of contact of individuals, the family, and the national health system bringing health care as close as possible to where people live and work, as the first element of a continuing health care process. . phc evolves from the conditions and characteristics of the country and its communities, based on the application of social, biomedical, and health services research and public health experience. . phc addresses the main health problems in the community, providing promotive, preventive, curative, and rehabilitative services accordingly. . phc includes the following: (a) education concerning prevailing health problems and methods of preventing and controlling them (b) promotion of food supply and proper nutrition (c) adequate supply of safe water and basic sanitation (d) maternal and child health care, including family planning (e) immunization against the major infectious diseases (f) prevention of locally endemic diseases (g) appropriate treatment of common diseases and injuries (h) the provision of essential drugs (i) relies on all health workers … to work as a health team. . all governments should formulate national health policies, strategies and plans, mobilize political will and resources, used rationally, to ensure phc for all people. national health planning. reforms of the nhs -for example, as discussed in chapter , remuneration increases for family physicians and encouraging group practice with public health nursing support -have become widespread in the uk. leading health maintenance organizations, such as kaiser permanente in the usa and district health systems in canada, have emphasized integrated approaches to health care for registered or geographically defined populations (see chapters - ). this approach is becoming common in the usa in acos, which will be fostered by the obamacare legislation (ppaca). this systematic approach to individual and community health is an integral part of the new public health. the interactions among community public health, personal health services, and health-related behavior, including their management, are the essence of the new public health. how the health system is organized and managed affects the health of the individual and the population, as does the quality of providers. health information systems with epidemiological, economic, and sociodemographic analysis are vital to monitor health status and allow for changing priorities and management. well-qualified personnel are essential to provide services, manage the system, and carry out relevant research and health policy analysis. diffusion of data, health information, and responsibility helps to provide a responsive and comprehensive approach to meet the health needs of the individual and community. the physical, social, economic, and political environments are all important determinants of the health status of the population and the individual. joint action (intersectoral cooperation) between public and non-governmental or community-based organizations is needed to achieve the well-being of the individual in a healthy society. in the s and s, these ideas contributed to an evolving new public health, spurred on by epidemiological changes, health economics, the development of managed care linking health systems, and prepayment. knowledge and self-care skills, as well as community action to reduce health risks, are no less important in this than the roles of medical practitioners and institutional care. all are parts of a coherent holistic approach to health. the concept of selective primary care, articulated in by walsh and warren, addresses the needs of developing countries to select those interventions on a broad scale that would have the greatest positive impact on health, taking into account limited resources such as money, facilities, and human resources. the term selective primary care is meant to define national priorities that are based not on the greatest causes of morbidity or mortality, but on common conditions of epidemiological importance for which there are effective and simple preventive measures. throughout health planning, there is an implicit or explicit selection of priorities for allocation of resources. even in primary care, selection of targets is a part of the process of resource allocation. in modern public health, this process is more explicit. a country with limited resources and a high birth rate will emphasize maternal and child health before investing in geriatric care. this concept has become part of the microeconomics of health care and technology assessment, discussed in chapters and , respectively, and is used widely in setting priorities and resource allocation. in developing countries, cost-effective primary care interventions have been articulated by many international organizations, including iodization of salt, use of oral rehydration therapy (ort) for diarrheal diseases, vitamin a supplementation for all children, expanded programs of immunization, and others that have the potential for saving hundreds of thousands of lives yearly at low cost. in developed countries, health promotions targeted to reduce accidents and risk factors such as smoking, high-fat diets, and lack of exercise for cardiovascular diseases are low-cost public health interventions that save lives and reduce the use of hospital care. targeting specific diseases is essential for efforts to control tb or eradicate polio, but at the same time, development of a comprehensive primary care infrastructure is equally or even more important than the single-disease approach. some disease entities such as hiv/aids attract donor funding more readily than basic infrastructure services such as immunization, and this can sometimes be detrimental to addressing the overall health needs of the population and other neglected but also important diseases. the risk approach selects population groups on the basis of risk and helps to determine interventional priorities to reduce morbidity and mortality. the measure of health risk is taken as a proxy for need, so that the risk approach provides something for all, but more for those in need, in proportion to that need. in epidemiological terms, these are people with higher relative risk or attributed risk. some groups in the general population are at higher risk than others for specific conditions. the expanded programme on immunization (epi), control of diarrhoeal diseases (cdd), and acute respiratory disease (ard) programs of the who are risk approaches to tackling fundamental public health problems of children in developing countries. public health places considerable emphasis on maternal and child health because these are vulnerable periods in life for specific health problems. pregnancy care is based on a basic level of care for all, with continuous assessment of risk factors that require a higher intensity of follow-up. prenatal care helps to identify factors that increase the risk for the pregnant woman or her fetus/newborn. efforts directed towards these special risk groups have the potential to reduce morbidity and mortality. high-risk case identification, assessment, and management are vital to a successful maternal care program. similarly, routine infant care is designed not only to promote the health of infants, but also to find the earliest possible indications of deviation and the need for further assessment and intervention to prevent a worsening of the condition. low birth-weight babies are at greater risk for many short-and long-term hazards and should be given special treatment. all babies are routinely screened for birth defects or congenital conditions such as hypothyroidism, phenylketonuria, and other metabolic and hematological diseases. screening must be followed by investigating and treating those found to have a clinical deficiency. this is an important element of infant care because infancy itself is a risk factor. as will be discussed in chapters and and others, epidemiology has come to focus on the risk approach with screening based on known genetic, social, nutritional, environmental, occupational, behavioral, or other factors contributing to the risk for disease. the risk approach has the advantage of specificity and is often used to initiate new programs directed at special categories of need. this approach can lead to narrow and somewhat rigid programs that may be difficult to integrate into a more general or comprehensive approach, but until universal programs can be achieved, selective targeted approaches are justifiable. indeed, even with universal health coverage, it is still important to address the health needs or issues of groups at special risk. working to achieve defined targets means making difficult choices. the supply and utilization of some services will limit availability for other services. there is an interaction, sometimes positive, sometimes negative, between competing needs and the health status of a population. public health identifies needs by measuring and comparing the incidence or prevalence of the condition in a defined population with that in other comparable population groups and defines targets to reduce or eliminate the risk of disease. it determines ways of intervening in the natural epidemiology of the disease, and develops a program to reduce or even eliminate the disease. it also assesses the outcomes in terms of reduced morbidity and mortality, as well as the economic justification in cost-effectiveness analysis to establish its value in health priorities. because of the interdependence of health services, as well as the total financial burden of health care, it is essential to look at the costs of providing health care, and how resources should be allocated to achieve the best results possible. health economics has become a fundamental methodology in policy determination. the costs of health care, the supply of services, the needs for health care or other health-promoting interventions, and effective means of using resources to meet goals are fundamental in the new public health. it is possible to err widely in health planning if one set of factors is overemphasized or underemphasized. excessive supply of one service diminishes the availability of resources for other needed investments in health. if diseases are not prevented or their sequelae not well managed, patients must use costly health care services and are unable to perform their normal social functions such as learning at school or performing at work. lack of investment in health promotion and primary prevention creates a larger reliance on institutional care, driving health costs upwards, and restricting flexibility in meeting patients' needs. the interaction of supply and demand for health services is an important determinant of the political economy of health care. health and its place in national priorities are determined by the social-political philosophy and resource allocation of a government. the case for action, or the justification for a public health intervention, is a complex of epidemiological, economic, and public policy factors (table . ). each disease or group of diseases requires its own case for action. the justification for public health intervention requires sufficient evidence of the incidence and prevalence of the disease (see chapter ). evidence-based public health takes into account the effectiveness and safety of an intervention; risk factors; safe means at hand to intervene; the human, social, and economic cost of the disease; political factors; and a policy decision as to the priority of the problem. this often depends on subjective factors, such as the guiding philosophy of the health system and the way it allocates resources. some interventions are so well established that no new justification is required to make the case, and the only question is how to do it most effectively. for example, infant vaccination is a cost-effective and cost-beneficial program for the protection of the individual child and the population as a whole. whether provided as a public service or as a clinical preventive measure by a private medical practitioner, it is in the interest of public health that all children be immunized. an outbreak of diarrheal disease in a kindergarten presents an obvious case for action, and a public health system must respond on an emergency basis, with selection of the most suitable mode of intervention. the considerations in developing a case for action are outlined above. need is based on clinical and epidemiological evidence, but also on the importance of an intervention in the eyes of the public. the technology available, its effectiveness and safety, and accumulated experience are important in the equation, as are the acceptability and affordability of appropriate interventions. the precedents for use of an intervention are also important. on epidemiological evidence, if the preventive practice has been seen to provide reduction in risk for the individual and for the population, then there is good reason to implement it. the costs, risks and benefits must be examined as part of the justification to help in the selection of health priorities. health systems research examines the efficiency of health care and promotes improved efficiency and effective use of resources. this is a vital function in determining how best to use resources and meet current health needs. past emphasis on hospital care at the expense of less development of primary care and prevention is still a common issue, particularly in former soviet and developing countries, where a high percentage of total health expenditure goes to acute hospital care with long length of stay, with smaller allocation to preventive and community health care. the result of this imbalance is high mortality from preventable diseases. new drugs, vaccines, and medical equipment are continually becoming available, and each new addition needs to be examined among the national health priorities. sometimes, owing to cost, a country cannot afford to add a new vaccine to the routine. however, when there is good evidence for efficacy and safety of new vaccines, drugs, diagnostic methods or other innovations, it could be applied for those at greatest risk. although there are ethical issues involved, it may be necessary to advise parents or family members to purchase the vaccine independently. clearly, recommending individual purchase of a vaccine is counter to the principle of equity and solidarity, benefiting middleclass families, and providing a poor basis of data for evaluation of the vaccine and its target disease. on the other hand, failure to advise parents of potential benefits to their children creates other ethical problems, but may increase public pressure and insurance system acceptance of new methods, e.g., varicella and hpv vaccines. mass screening programs involving complete physical examinations have not been found to be cost-effective or to significantly reduce disease. in the s and s, routine general health examinations were promoted as an effective method of finding disease early. since the late s, a selective and specific approach to screening has become widely accepted. this involves defining risk categories for specific diseases and bearing in mind the potential for remedial action. early case finding of colon cancer by routine fecal blood testing and colonoscopy has been found to be effective, and pap smear testing to discover cancer of the cervix is timed according to risk category. screening for colorectal cancer is essential for modern health programs and has been adopted by most industrialized countries. outreach programs by visits, telephones, emails or other modern methods of communication are important to contact non-attenders to promote utilization, and have been shown to increase compliance with proven effective measures. these programs are important for screening, follow-up, and maintenance of treatment for hypertension, diabetes, and other conditions requiring long-term management. screening technology is changing and often the subject of intense debate as such programs are costly and their cost-effectiveness is an important matter for policy making: screening for lung cancer is becoming a feasible and effective matter for high-risk groups, whereas breast cancer screening frequency is now in dispute; while nanotechnology and bioengineering promises new methods for cancer screening. the factor of contribution to quality of life should be considered. a vaccine for varicella is justified partly for the prevention of deaths or illness from chickenpox. a stronger the right to health public expectation and social norms argument is often based on the fact that this is a disease that causes moderate illness in children for up to weeks and may require parents to stay home with the child, resulting in economic loss to the parent and society. the fact that this vaccination prevents the occurrence of herpes zoster or shingles later in life may also be a justification. widespread adoption of hepatitis b vaccine is justified on the grounds that it prevents cancer of the liver, liver cirrhosis, and hepatic failure in a high percentage of the population affected. how many cases of a disease are enough to justify an intervention? one or several cases of some diseases, such as poliomyelitis, may be considered an epidemic in that each case constitutes or is an indicator of a wider threat. a single case of polio suggests that another persons are infected but have not developed a recognized clinical condition. such a case constitutes a public health emergency, and forceful organization to meet a crisis is needed. current standards are such that even one case of measles imported into a population free of the disease may cause a large outbreak, as occurred in the uk, france, and israel during through , by contacts on an aircraft, at family gatherings, or even in medical settings. a measles epidemic indicates a failure of public health policy and practice. screening for some cancers, such as cervix and colon, is cost effective. screening of all newborns for congenital disorders is important because each case discovered early and treated effectively saves a lifetime of care for serious disability. assessing a public health intervention to prevent the disease or reduce its impact requires measurement of the disease in the population and its economic impact. there is no simple formula to justify a particular intervention, but the cost-benefit approach is now commonly required to make such a case for action. sometimes public opinion and political leadership may oppose the views of the professional community, or may impose limitations of policy or funds that prevent its implementation. conversely, professional groups may press for additional resources that compete for limited resources available to provide other needed health activities. both the professionals of the health system and the general public need full access to health-related information to take part in such debates in a constructive way. to maintain progress, a system must examine new technologies and justify their adoption or rejection (see chapter ). the association between health and political issues was emphasized by european innovators such as rudolf virchow (and in great britain by edwin chadwick; see chapter ) in the mid-nineteenth century, when the conditions of the working population were such that epidemic diseases were rife and mortality was high, especially in the crowded slums of the industrial revolution. the same observations led bismarck in germany to introduce early forms of social insurance for the health of workers and their families in the s, and to britain's national health insurance, also for workers and families. the role of government in providing universal access to health care was a struggle in individual countries during the twentieth century and lasting into the second decade of the twenty-first century (e.g. president obama's affordable health care act of ). as the concept of public health has evolved, and the cost effectiveness of medical care has improved through scientific and technological advances, societies have identified health as a legitimate area of activity for collective bargaining and government. with this process, the need to manage health care resources has become more clearly defined as a public responsibility. in industrialized countries, each with very different political make-up, national responsibility for universal access to health has become part of the social ethos. with that, the financing and managing of health services have developed into part of a broad concept of public health, and economics, planning, and management have come to be part of the new public health (discussed in chapters - ). social, ethical, and political philosophies have profound effects on policy decisions including allocation of public monies and resources. investment in public health is now recognized as an integral part of socioeconomic development. governments are major suppliers of funds and leadership in health infrastructure development, provision of health services, and health payment systems. they also play a central role in the development of health promotion and regulation of the environment, food, and drugs essential for community health. in liberal social democracies, the individual is deemed to have a right to health care. the state accepts responsibility to ensure availability, accessibility, and quality of care. in many developed countries, government has also taken responsibility to arrange funding and services that are equitably accessible and of high quality. health care financing may involve taxation, allocation, or special mandatory requirements on employers to pay for health insurance. services may be provided by a state-financed and -regulated service or through ngos and/or private service mechanisms. these systems allocate between percent and percent of gross national product (gnp) to health services, with some governments funding over percent of health expenditure; for example, canada and the uk. in communist states, the state organizes all aspects of health care with the philosophy that every citizen is entitled to equity in access to health services. the state health system manages research, staff training, and service delivery, even if operational aspects are decentralized to local health authorities. this model applied primarily to the soviet model of health services. these systems, except for cuba, placed financing of health low on the national priority, with funding less than percent of gnp. in the shift to market economies in the s, some former socialist countries, such as russia, are struggling with poor health status and a difficult shift from a strongly centralized health system to a decentralized system with diffusion of powers and responsibilities. promotion of market concepts in former soviet countries has reduced access to care and created a serious dilemma for their governments. former colonial countries, independent since the s and s, largely carried on the governmental health structures established in the colonial times. most developing countries have given health a relatively low place in budgetary allotment, with expenditures under percent of gnp. since the s, there has been a trend in developing countries towards decentralization of health services and greater roles for ngos, and the development of health insurance. some countries, influenced by medical concepts of their former colonial master countries, fostered the development of specialty medicine in the major centers with little emphasis on the rural majority population. soviet influence in many ex-colonial countries promoted state-operated systems. the who promoted primary care, but the allocations favored city-based specialty care. israel, as an ex-colony, adapted british ideas of public health together with central european sick funds and maternal and child health as major streams of development until the mid- s. a growing new conservatism in the s and s in the industrialized countries is a restatement of old values in which market economics and individualistic social values are placed above concepts of the "common good" of liberalism and socialism in its various forms. in the more extreme forms of this concept, the individual is responsible for his or her own health, including payment, and has a choice of health care providers that will respond with high-quality personalized care. market forces, meaning competition in financing and provision of health services with rationing of services, based on fees or private insurance and willingness and ability to pay, have become part of the ideology of the new conservatism. it is assumed that the patient (i.e., the consumer) will select the best service for his or her need, while the provider best able to meet consumer expectations will thrive. in its purest form, the state has no role in providing or financing of health services except those directly related to community protection and promotion of a healthful environment without interfering with individual choices. the state ensures that there are sufficient health care providers and allows market forces to determine the prices and distribution of services with minimal regulation. the usa retains this orientation in a highly modified form, with percent of the population covered by some form of private or public insurance systems (see chapters and ). modified market forces in health care are part of health reforms in many countries as they seek not only to ensure quality health care for all but also to constrain costs. a free market in health care is costly and ultimately inefficient because it encourages inflation of provider incomes or budgets and increasing utilization of highly technical services. further, even in the most free market societies, the economy of health care is highly influenced by many factors outside the control of the consumer and provider. the total national health expenditure in the usa rose rapidly until reaching over . percent of gross domestic product (gdp) in , the highest of any country, despite serious deficiencies for those without any or with very inadequate health insurance (in total more than percent of the population). this figure compares to some . percent of gdp in canada, which has universal health insurance under public administration. following the defeat of president clinton's national health program, the conservative congress and the business community took steps to expand managed care in order to control costs, resulting in a revolution in health care in the usa (see chapters and ). in the - decade health expenditure in the usa is expected to rise to . percent of gdp, partly owing to increased population coverage with implementation of the ppaca (obamacare). reforms are being implemented in many "socialized" health systems. these may be through incentives to promote achievement of performance indicators, such as full immunization coverage. others are using control of supply, such as hospital beds or licensed physicians, as methods of reducing overutilization of services that generates increasing costs. market mechanisms in health are aimed not only at the individual but also at the provider. incentive payment systems must work to protect the patient's legitimate needs, and conversely incentives that might reduce quality of care should be avoided. fee-for-service promotes high rates of services such as surgery. increasing private practice and user fees can adversely affect middle-and low-income groups, as well as employers, by raising the costs of health insurance. managed care systems, with restraints on fee-for-service medical practice, have emerged as a positive response to the market approach. incentive systems in payments for services may be altered by government or insurance agencies in order to promote rational use of services, such as reduction of hospital stays. the free market approach is affecting planning of health insurance systems in previously highly centralized health systems in developing countries as well as the redevelopment of health systems in former soviet countries. despite political differences, reform of health systems has become a common factor in virtually all health systems since the s, as each government searches for costeffectiveness, quality of care, and universality of coverage. the new paradigm of health care reform sees the convergence of different systems to common principles. national responsibility for health goals and health promotion leads to national financing of health care with regional and managed care systems. most developed countries have long since adopted national health insurance or service systems. some governments may, as in the usa, insure only the highest risk groups such as the elderly and the poor, leaving the working and middle classes to seek private insurers. the nature and direction of health care reform affecting coverage of the population are of central importance in the new public health because of its effects on allocation of resources and on the health of the population. the effects of the economic crisis in the usa are being felt worldwide. while the downturn has largely occurred in wealthier nations, the poor in low-income countries will be among those affected. past economic downturns have been followed by substantial drops in foreign aid to developing countries. as public health gained from sanitary and other control measures for infectious diseases, along with mother and child care, nutrition, and environmental and occupational health, it also gained strength and applicability from advances in the social and behavioral sciences. social darwinism, a political philosophy that assumed "survival of the fittest" and no intervention of the sate to alleviate this assumption, was popular in the early nineteenth century but became unacceptable in industrialized countries, which adopted social policies to alleviate the worst conditions of poverty, unemployment, poor education, and other societal ills. the political approach to focusing on health and poverty is associated with jeremy bentham in britain in the late eighteenth century, who promoted social and political reform and "the greatest good for the greatest number", or utilitarianism. rudolf virchow, an eminent pathologist and a leader in recognizing ill-health and poverty as cause and effect, called for political action to create better conditions for the poor and working-class population. the struggle for a social contract was promoted by pioneer reformists such as edwin chadwick (general report on the sanitary condition of the labouring population of great britain, ), who later became the first head of the board of health in britain, and lemuel shattuck (report of a general plan for the promotion of public and personal health, ) . shattuck was the organizer and first president of the american statistical association. the social sciences have become fundamental to public health, with a range of disciplines including vital statistics and demography (seventeenth century), economics and politics (nineteenth century), sociology (twentieth century), history, anthropology, and others, which provide collectively important elements of epidemiology of crucial significance for survey methods and qualitative research (see chapter ). these advances contributed greatly to the development of methods of studying diseases and risk factors in a population and are still highly relevant to addressing inequalities in health. individuals in good health are better able to study and learn, and be more productive in their work. improvements in the standard of living have long been known to contribute to improved public health; however, the converse has not always been recognized. investment in health care was not considered a high priority in many countries where economic considerations directed investment to the "productive" sectors such as manufacturing and large-scale infrastructure projects, such as hydroelectric dams. whether health is a contributor to economic development or a drain on societies' resources has been a fundamental debate between socially and market-oriented advocates. classic economic theory, both free enterprise and communist, has tended to regard health as a drain on economies, distracting investment needed for economic growth. as a result, in many countries health has been given low priority in budgetary allocation, even when the major source of financing is governmental. this belief among economists and banking institutions prevented loans for health development on the grounds that such funds should focus on creating jobs and better incomes, before investing in health infrastructure. consequently, the development of health care has been hampered. a socially oriented approach sees investment in health as necessary for the protection and development of "human capital", just as investment in education is needed for the long-term benefit of the economy of a country. in , the world bank's world development report: investing in health articulated a new approach to economics in which health, along with education and social development, is seen as an essential precondition for and contributor to economic development. while many in the health field have long recognized the importance of health for social and economic improvement, its adoption by leading international development banking may mark a turning point for investment in developing nations, so that health may be a contender for increased development loans. the concept of an essential package of services discussed in that report establishes priorities in low-and middle-income countries for efficient use of resources based on the burden of disease and cost-effectiveness analysis of services. it includes both preventive and curative services targeted to specific health problems. it also recommends support for comprehensive primary care, such as for children, and infrastructure development including maternity and hospital care, medical and nursing outreach services, and community action to improve sanitation and safe water supplies. reorientation of government spending on health is increasingly being adopted, as in the uk, to improve equity in access for the poor and other neglected sectors or regions of society with added funding for relatively deprived areas to improve primary care services. differential capitation funding as a form of affirmative action to provide for highneeds populations is a useful concept in public health terms to address the inequities still prevalent in many countries. as medical care has gradually become more involved in prevention, and as it has moved into the era of managed care, the gap between public health and clinical medicine has narrowed. as noted above, many countries are engaged in reforms in their health care systems. the motivation is largely derived from the need for cost containment, but also to extend health care coverage to underserved parts of the population. countries without universal health care still have serious inequities in distribution of or access to services, and may seek reform to reduce those inequities, perhaps under political pressures to improve the provision of services. incentives for reform are needed to address regional inequities, and preserving or developing universal access and quality of care, but also on inequities in health between the rich and the poor countries and within even the wealthy countries. in some settings, a health system may fail to keep pace with developments in prevention and in clinical medicine. some countries have overdeveloped medical and hospital care, neglecting important initiatives to reduce the risk of disease. the process of reform requires setting standards to measure health status and the balance of services to optimize health. a health service can set a target of immunizing percent of infants with a national immunization schedule, but requires a system to monitor performance and incentives for changes. a health system may also have failed to adapt to changing needs of the population through lack, or misuse, of health information and monitoring systems. as a result, the system may err seriously in its allocation of resources, with excessive emphasis on hospital care and insufficient attention to primary and preventive care. all health services should have mechanisms for correctly gathering and analyzing needed data for monitoring the incidence of disease and other health indicators, such as hospital utilization, ambulatory care, and preventive care patterns. for example, the uk's nhs periodically undertakes a restructuring process of parts of the system to improve the efficiency of service. this involves organizational changes and decentralization with regional allocation of resources (see chapter ). health systems are under pressures of changing demographic and epidemiological patterns as well as public expectations, rising costs of new technology, financing, and organizational change. new problems must be continually addressed with selection of priority issues and the most effective methods chosen. reforms may create unanticipated problems, such as professional or public dissatisfaction, which must be evaluated, monitored, and addressed as part of the evolution of public health. literacy, freedom of the press, and increasing public concern for social and health issues have contributed to the development of public health. the british medical community lobbied for restrictions on the sale of gin in the s in order to reduce the damage that it caused to the working class. in the late eighteenth and the nineteenth centuries, reforms in society and sanitation were largely the result of strongly organized advocacy groups influencing public opinion through the press. such pressure stimulated governments to act in regulating the working conditions of mines and factories. abolition of the slave trade and its suppression by the british navy in the early nineteenth century resulted from successful advocacy groups and their effects on public opinion through the press. vaccination against smallpox was promoted by privately organized citizen groups, until later taken up by local and national government authorities. advocacy consists of activities of individuals or groups publicly pleading for, supporting, espousing, or recommending a cause or course of action. the advocacy role of reform movements in the nineteenth century was the basis of the development of modern organized public health. campaigns ranged from the reform of mental hospitals, nutrition for sailors to prevent scurvy and beriberi, and labor laws to improve working conditions for women and children in particular, to the promotion of universal education and improved living conditions for the working population. reforms on these and other issues resulted from the stirring of the public consciousness by advocacy groups and the public media, all of which generated political decisions in parliaments (box . ). such reforms were in large part motivated by fear of revolution throughout europe in the mid-nineteenth century and the early part of the twentieth century. trade unions, and before them medieval guilds, fought to improve hours, safety, and conditions of work, as well as social and health benefits for their members. in the usa, collective bargaining through trade unions achieved wage increases and widespread coverage of the working population under voluntary health insurance. unions and some industries pioneered prepaid group practice, the predecessor of health maintenance organizations and managed care or the more recent acos (see chapters and ). through raising public consciousness on many issues, advocacy groups pressure governments to enact legislation to restrict smoking in public places, prohibit tobacco advertising, and mandate the use of bicycle helmets. advocacy groups play an important role in advancing health based on disease groups, such as cancer, multiple sclerosis, and thalassemia, or advancing health issues, such as the organizations promoting breastfeeding, environmental improvement, or smoking reduction. some organizations finance services or facilities not usually provided within insured health programs. such organizations, which can number in the hundreds in a country, advocate the importance of their special concern and play an important role in innovation and meeting community health needs. advocacy groups, including trade unions, professional groups, women's groups, self-help groups, and many others, focus on specific issues and have made major contributions to advancing the new public health. the history of public health is replete with pioneers whose discoveries led to strong opposition and sometimes violent rejection by conservative elements and vested interests in medical, public, or political circles. opposition to jennerian vaccination, the rejection of semmelweiss by colleagues in vienna, and the contemporary opposition to the work of great pioneers in public health such as pasteur, florence nightingale, and many others may deter or delay implementation of other innovators and new breakthroughs in preventing disease. although opposition to jenner's vaccination lasted well into the late nineteenth century in some areas, its supporters gradually gained ascendancy, ultimately leading to the global eradication of smallpox. these and other pioneers led the way to improved health, often after bitter controversy on topics later accepted and which, in retrospect, seem to be obvious. advocacy has sometimes had the support of the medical profession but elicited a slow response from public authorities. david marine of the cleveland clinic and david cowie, professor of pediatrics at the university of michigan, proposed the prevention of goiter by iodization of salt. marine carried out a series of studies in fish, and then in a controlled clinical trial among schoolgirls in - , with startlingly positive results in reducing the prevalence of goiter. cowie campaigned for the iodization of salt, with support from the medical profession. in , he convinced a private manufacturer to produce morton's iodized salt, which rapidly became popular throughout north america. similarly, iodized salt came to be used in many parts of europe, mostly without governmental support or legislation. iodine-deficiency disorders (idds) remain a widespread condition, estimated to have affected billion people worldwide in . the target of international eradication of idds by was set at the world summit for children in , and the who called for universal iodization of salt in . by , nearly percent of households in developing countries consumed adequately iodized salt. china and nigeria, have had great success in recent years with mandatory salt fortification in increasing iodization rates, in china from percent to percent in years. but the problem is not yet gone and even in europe there is inadequate standardization of iodine levels and population follow-up despite decades of work on the problem. professional organizations have contributed to promoting causes such as children's and women's health, and environmental and occupational health. the american academy of pediatrics has contributed to establishing and promoting high standards of care for infants and children in the usa, and to child health internationally. hospital accreditation has been used for decades in the usa, canada, and more recently in australia and the uk. it has helped to raise standards of health facilities and care by carrying out systematic peer review of hospitals, nursing homes, primary care facilities, and mental hospitals, as well as ambulatory care centers and public health agencies (see chapter ). public health needs to be aware of negative advocacy, sometimes based on professional conservatism or economic self-interest. professional organizations can also serve as advocates of the status quo in the face of change. opposition by the american medical association (ama) and the health insurance industry to national health insurance in the usa has been strong and successful for many decades. the passage of the ppaca has been achieved despite widespread political and public opposition, yet was sustained in the us supreme court and is gaining widening popular support as the added value to millions of formerly uninsured americans becomes clear. in some cases, the vested interest of one profession may block the legitimate development of others, such as when ophthalmologists lobbied successfully against the development of optometry, now widely accepted as a legitimate profession. political activism for reform in nineteenth-century britain led to banning and suppressing the slave trade, improvements in working conditions for miners and factory workers, and other major political reforms. in keeping with this tradition, samuel plimsoll ( - ), british member of parliament elected for derby in , conducted a solo campaign for the safety of seamen. his book, our seamen, described ships sent to sea so heavily laden with coal and iron that their decks were awash. seriously overloaded ships, deliberately sent to sea by unscrupulous owners, frequently capsized, drowning many crew members, with the owners collecting inflated insurance fees. overloading was the major cause of wrecks and thousands of deaths in the british shipping industry. plimsoll pleaded for mandatory load-line certificate markers to be issued to each ship to prevent any ships putting to sea when the marker was not clearly visible. powerful shipping interests fought him every inch of the way, but he succeeded in having a royal commission established, leading to an act of parliament mandating the "plimsoll line", the safe carrying capacity of cargo ships. this regulation was adopted by the us bureau of shipping as the load line act in and is now standard practice worldwide. jenner's discovery of vaccination with cowpox to prevent smallpox was adopted rapidly and widely. however, intense opposition by organized groups of antivaccinationists, often led by those opposed to government intervention in health issues and supported by doctors with lucrative variolation practices, delayed the implementation of smallpox vaccination for many decades. ultimately, smallpox was eradicated in , owing to a global campaign initiated by the who. opposition to legislated restrictions on private ownership of assault weapons and handguns is intense in the usa, led by well-organized, well-funded, and politically powerful lobby groups, despite the amount of morbidity and mortality due to gun-associated violent acts (see chapter ). fluoridation of drinking water is the most effective public health measure for preventing dental caries, but it is still widely opposed, and in some places the legislation has been rescinded even after implementation, by wellorganized antifluoridation campaigns. opposition to fluoridation of community water supplies is widespread, and effective lobbying internationally has slowed but has not stopped progress (see chapter ). despite the life-saving value of immunization, opposition still exists in and harms public health protection. opposition has slowed progress in poliomyelitis eradication; for example, radical islamists killed polio workers in northern nigeria in , one of the last three countries with endemic poliomyelitis. resistance to immunization in the s has resulted in the recurrence of pertussis and diphtheria and a very large epidemic of measles across western europe, including the uk, with further spread to the western hemisphere in - (see chapter ). progress may be blocked where all decisions are made in closed discussions, not subject to open scrutiny and debate. public health personnel working in the civil service of organized systems of government may not be at liberty to promote public health causes. however, professional organizations may then serve as forums for the essential professional and public debate needed for progress in the field. professional organizations such as the apha provide effective lobbying for the interests of public health programs and can have an important impact on public policy. in mid- , efforts by the secretary of health and human services in the usa brought together leaders of public health with representatives of the ama and academic medical centers to try to find areas of common interest and willingness to promote the health of the population. in europe too, increasing cooperation between public health organizations is stimulating debate on issues of transnational importance across the region, which, for example, has a wide diversity of standards on immunization practices and food policies. public advocacy has played an especially important role in focusing attention on ecological issues (box . ). in , greenpeace, an international environmental activist group, fought to prevent the dumping of an oil rig in the north sea and forced a major oil company to find another solution that would be less damaging to the environment. an explosion on an oil rig in the gulf of mexico in led to enormous ecological and economic damage as well as loss of life. damages levied on the responsible company (british petroleum) amount to some $ . billion dollars and several criminal negligence charges are pending. greenpeace also continued its efforts to stop the renewal of testing of atomic bombs by france in the south pacific. international protests led to the cessation of almost all testing of nuclear weapons. international concern over global warming has led to growing efforts to stem the tide of air pollution from fossil fuels, coal-burning electrical production, and other manifestations of carbon dioxide and toxic contamination of the environment. progress is far from certain as newly enriched countries such as china and india follow the rising consumption patterns of western countries. public advocacy and rejection of wanton destruction of the global ecology may be the only way to prod consumers, governments, and corporate entities such as the energy and transportation industries to change direction. the pace of change from fossil fuels is slow but has captured public attention, and private companies are seeking more fuel efficiency in vehicles and electrical power production, mainly though the use of natural gas instead of fuel oil and coal for electricity production or better still by wind and solar energy. the search for "green solutions" to the global warming crisis has become increasingly dynamic, with governments, the private sector, and the general public keenly aware of the importance of the effort and the dangers of failure. in the latter part of the twentieth century and the early twenty-first century, prominent international personalities and entertainers have taken up causes such as the removal of land mines in war-torn countries, illiteracy in disadvantaged advocacy is a function in public health that has been important in promoting advances in the field, and one that sometimes places the advocate in conflict with established patterns and organizations. one of the classic descriptions of this function is in henrik ibsen's play an enemy of the people, in which the hero, a young doctor, thomas stockmann, discovers that the water in his community is contaminated. this knowledge is suppressed by the town's leadership, led by his brother the mayor, because it would adversely affect plans to develop a tourist industry of baths in their small norwegian town in the late nineteenth century. the young doctor is taunted and abused by the townspeople and driven from the town, having been declared an "enemy of the people" and a potential risk. the allegory is a tribute to the man of principle who stands against the hysteria of the crowd. the term also took on a far more sinister and dangerous meaning in george orwell's novel and in totalitarian regimes of the s to the present time. populations, and funding for antiretroviral drugs for african countries to reduce maternal-fetal transmission of hiv and to provide care for the large numbers of cases of aids devastating many countries of sub-saharan africa. rotary international has played a key role in polio eradication efforts globally. the public-private consortium global alliance for vaccines and immunization (gavi) has been instrumental in promoting immunization in recent years, with participation by the who, unicef, the world bank, the gates foundation, vaccine manufacturers, and others. this has had an important impact on extending immunization to protect and save the lives of millions of children in deprived countries not yet able to provide fundamental prevention programs such as immunization at adequate levels. gavi has brought vaccines to low-income countries around the world, such as rotavirus vaccine, pentavalent vaccine in myanmar, and pneumococcal vaccine for children in countries in sub-saharan africa, including dr congo. the bill & melinda gates foundation pledged us $ million in to establish gavi, with us $ million per year and us $ billion in to promote the decade of vaccines. international conferences help to create a worldwide climate of advocacy for health issues. international sanitary conferences in the nineteenth century were convened in response to the cholera epidemics. international conferences continue in the twenty-first century to serve as venues for advocacy on a global scale, bringing forward issues in public health that are beyond the scope of individual nations. the who, unicef, and other international organizations perform this role on a continuing basis (see chapter ). criticisms of this approach have focused on the lack of similar effort or donors to address ncds, weak public health infrastructure, and that this frees national governments from responsibility to care for their own children. no one can question, however, that this kind of endeavor has saved countless lives and needs the backing of other aid donors and national government participation. consumerism is a movement that promotes the interests of the purchaser of goods or services. in the s, a new form of consumer advocacy emerged from the civil rights and antiwar movement in the usa. concern was focused on the environment, occupational health, and the rights of the consumer. rachel carson stimulated concern by dramatizing the effects of ddt on wildlife and the environment but inadvertently jeopardized anti-malarial efforts in many countries. this period gave rise to environmental advocacy efforts worldwide, and a political movement, the greens, in western europe. ralph nader showed the power of the advocate or "whistle-blower" who publicizes health hazards to stimulate active public debate on a host of issues related to the public well-being. nader, a consumer advocate lawyer, developed a strategy for fighting against business and government activities and products which endangered public health and safety. his book unsafe at any speed took issue with the us automobile industry for emphasizing profit and style over safety, and led to the enactment of the national traffic and motor safety act of , establishing safety standards for new cars. this was followed by a series of enactments including design and emission standards and seat-belt regulations. nader's work continues to promote consumer interests in a wide variety of fields, including the meat and poultry industries, and coal mining, and promotes greater government regulatory powers regarding pesticide usage, food additives, consumer protection laws, rights to knowledge of contents, and safety standards. consumerism has become an integral part of free market economies, and the educated consumer does influence the quality, content, and price of products. greater awareness of nutrition in health has influenced food manufacturers to improve packaging, content labeling, enrichment with vitamins and minerals, and advertisement to promote those values. low-fat dietary products are available because of an increasingly sophisticated public concerned over dietary factors in cardiovascular diseases. the same process occurred in safe toys and clothing for children, automobile safety features such as mandatory use of car seats for infants, and other innovations that quickly became industry standards in the industrialized world. dangerous practices such as the use of lead paint in toys and melamine contamination of milk products from china capture the public attention quickly and remind public health authorities of the importance of continuous alertness to potential hazards. consumerism can also be exploited by pharmaceutical companies with negative impacts on the health system, especially in the advertising of health products which leads to unnecessary visits to health providers and pressure for approval to obtain the product. the internet has provided people with access to a vast array of information and opinion, and to current literature otherwise unavailable because of the often inadequate library resources of medical and other health professionals. the very freedom of information the internet allows, however, also provides a vehicle for extremist and fringe groups to promote disinformation such as "vaccination causes autism, fluoridation causes cancer", which can cause considerable difficulties for basic public health programs or lead to self-diagnosis of conditions, with often disastrous consequences. advocacy and voluntarism go hand in hand. voluntarism takes many forms, including raising funds for the development of services or operating services needed in the community. it may take the form of fund-raising to build clinics or hospitals in the community, or to provide medical equipment for elderly or handicapped people; or retirees and teenagers working as hospital volunteers to provide services that are not available through paid staff, and to provide a sense of community caring for the sick in the best traditions of religious or municipal concerns. this can also be extended to prevention, as in support for immunization programs, assistance for the handicapped and elderly in transportation, meals-on-wheels, and many other services that may not be included in the "basket of services" provided by the state, health insurance, or public health services. community involvement can take many forms, and so can voluntarism. the pioneering role of women's organizations in promoting literacy, health services, and nutrition in north america during the latter part of the nineteenth and the early twentieth centuries profoundly affected the health of the population. the advocacy function is enhanced when an organization mobilizes voluntary activity and funds to promote changes or needed services, sometimes forcing official health agencies or insurance systems to revise their attitudes and programs to meet these needs. by the early s, canada's system of federally supported provincial health insurance plans covered all of the country. the federal minister of health, marc lalonde, initiated a review of the national health situation, in view of concern over the rapidly increasing costs of health care. this led to articulation of the "health field concept" in , which defined health as a result of four major factors: human biology, environment, behavior, and health care organization (box . ). lifestyle and environmental factors were seen as important contributors to the morbidity and mortality in modern societies. this concept gained wide acceptance, promoting new initiatives that emphasized health promotion in response to environmental and lifestyle factors. conversely, reliance primarily on medical care to solve all health problems could be counterproductive. this concept was a fundamental contributor to the idea of health promotion later articulated in the ottawa declaration, discussed below. the health field concept came at a time when many epidemiological studies were identifying risk factors for cardiovascular diseases and cancers that related to personal habits, such as diet, exercise, and smoking. the concept advocated that public policy needed to address individual lifestyle as part of the overall effort to improve health status. as a result, the canadian federal government established health promotion as a new activity. this quickly spread to many other jurisdictions and gained wide acceptance in many industrialized countries. concern was expressed that this concept could become a justification for a "blame the victim" approach, in which those ill with a disease related to personal lifestyles, such as smokers or aids patients, are seen as having chosen to contract the disease. such a patient might then be considered not to be entitled to all benefits of insurance or care that others may receive. the result may be a restrictive approach to care and treatment that would be unethical in the public health tradition and probably illegal in western jurisprudence. this concept was also used to justify withdrawal from federal commitments in cost sharing and escape from facing controversial health reform in the national health insurance program. during the s and s, outspoken critics of health care systems, such as ivan illytch, questioned the value of medical care for the health of the public. this became a widely discussed, somewhat nihilistic, view towards medical care, and was influential in promoting skepticism regarding the value of the biomedical mode of health care, and antagonism towards the medical profession. in , thomas mckeown presented a historicalepidemiological analysis showing that up to the s, medical care had only a limited impact on mortality rates, although improvements in surgery and obstetrics were notable. he showed that crude death rates in england averaged about per population from to , declining steeply to per in , per in , and per in , when medical care became truly effective. mckeown concluded that much of the improvement in health status over the past several centuries was due to reduced mortality from infectious diseases. this he related to limitation of family size, increased food supplies, improved nutrition and sanitation, specific preventive and therapeutic measures, and overall gains in quality of life for growing elements of the population. he cautioned against placing excessive reliance for health on medical care, much of which was of unproved effectiveness. this skepticism of the biomedical model of health care was part of wider antiestablishment feelings of the s and s in north america. in , milton roemer pointed out that the advent of vaccines, antibiotics, antihypertensives, and other medications contributed to great improvements in infant and child care, and in the management of infectious diseases, hypertension, diabetes, and other conditions. therapeutic gains continue to arrive from teaching centers around the world. vaccine, pharmaceutical, and diagnostic equipment manufacturers continue to provide important innovations that have major benefits, but also raise the cost of health care. the latter issue is one which has stimulated the search for reforms, and search for lower cost technologies such as in treatment of hepatitis c patients, a huge international public health issue. the value of medical care to public health and vice versa has not always been clear, either to public health personnel or to clinicians. the achievements of modern public health in controlling infectious diseases, and even more so in reducing the mortality and morbidity associated with chronic diseases such as stroke and chd, were in reality a shared achievement between clinical medicine and public health (see chapter ). preventive medicine has become part of all medical practice, with disease prevention through early diagnosis and health promotion through individual and community-focused activities. risk factor evaluation determines appropriate screening and individual and community-based interventions. medical care is crucial in controlling hypertension and in reducing the complications and mortality from chd. new modalities of treatment are reducing death rates from first time acute myocardial infarctions. better management of diabetes prevents the early onset of complications. at the same time, the contribution of public health to improving outcomes of medical care is equally important. control of the vaccine-preventable diseases, improved nutrition, and preparation for motherhood contribute to improved maternal and infant outcomes. promotions of reduced exposure to risk factors for chronic disease are a task shared by public health and clinical medical services. both clinical medicine and public health contribute to improved health status. they are interdependent and rely on funding systems for recognition as part of the new public health. during the s, many new management concepts emerged in the business community, such as "management by objective", a concept developed by peter drucker at general motors, with variants such as "zero-based budgeting" developed in the us department of defense (see chapter ). they focused the activities of an organization and its budget on targets, rather than on previous allocation of resources. these concepts were applied in other spheres, but they influenced thinking in health, whose professionals were seeking new ways to approach health planning. the logical application was to define health targets and to promote the efficient use of resources to achieve those targets. this occurred in the usa and soon afterwards in the who european region. in both cases, a wide-scale process of discussion and consensus building was used before reaching definitive targets. this process contributed to the adoption of the targets by many countries in europe as well as by states and many professional and consumer organizations. the usa developed national health objectives in for the year and subsequently for the year , with monitoring of progress in their achievement and development of further targets for and now for . beginning in , state health profiles are prepared by the epidemiology program office of the centers for disease control and prevention based on health indicators recommended by a consensus panel representing public health associations and organizations. the eight mdgs adopted by the un in include halving extreme poverty, reducing child mortality by twothirds, improving maternal health, halting the spread of hiv/aids, malaria, and other diseases, and providing universal primary education, all by the target date of . the mdgs form a common blueprint agreed to by all countries and the world's leading development institutions. the process has galvanized unprecedented efforts to meet the needs of the world's poorest, yet reviews of progress indicate that most developing nations will not meet the targets at current rates of progress. the united nations development programme (undp) global partnership for development report on the mdgs states that if the national development strategies and initiatives are supported by international development partners, the goals can be achieved by . the mdgs were adopted by over nations and provided guidance for national policies and for international aid agencies. the focus was on middle-and low-income countries and their achievements have been considerable but variable (see box . and chapter ) . as of july , extreme poverty was falling in every region, the poverty reduction target had been met, the world had met the target of halving the proportion of people without access to improved sources of water, and the world had achieved parity in primary education between girls and boys. further progress will require sustained political commitment to develop the primary care infrastructure: improved reporting and epidemiological monitoring, consultative mechanisms, and consensus by international agencies, national governments, and non-governmental agencies. the achievement of the targets will also require sustained international support and national commitment with all the difficulties of a time of economic recession. nevertheless, defining a target is crucial to the process. there are encouraging signs that national governments are influenced by the general movement to place greater emphasis on resource allocation and planning on primary care to achieve internationally recognized goals and targets. the successful elimination of smallpox, rising immunization coverage in the developing countries, and increasing implementation of salt iodization have shown that such goals are achievable. while the usa has not succeeded in developing universal health care access, it has a strong tradition of public health and health advocacy. federal, state, and local health authorities have worked out cooperative arrangements for financing and supervising public health and other services. with growing recognition in the s that medical services alone would not achieve better health results, health policy leadership in the federal government formulated a new approach, in the form of developing specific health targets for the nation. in , the surgeon general of the usa published the report on health promotion and disease prevention (healthy people). this document set five overall health goals for each of the major age groups for the year , accompanied by specific health objectives. new targets for the year were developed in three broad areas: to increase healthy lifespans, to reduce health disparities, and to achieve access to preventive health care for all americans. these broad goals are supported by specific targets in health priority areas, each one divided into four major categories: health promotion, health protection, preventive services, and surveillance systems. this set the public health agenda on the basis of measurable indicators that can be assessed year by year. reduce child mortality -progress on child mortality is gaining momentum. the target is to reduce by two-thirds, between and , the under- -year-old mortality rate, from children of every dying to of every . child deaths are falling, but much more needs to be done in order to reach the development goal. revitalizing efforts against pneumonia and diarrhea, while bolstering nutrition, could save millions of children. l mdg . improve maternal health -maternal mortality has nearly halved since , but levels are far removed from the target. the targets for improving maternal health include reducing by three-quarters the maternal mortality ratio and achieve universal access to reproductive health. poverty and lack of education perpetuate high adolescent birth rates. inadequate funding for family planning is a major failure in fulfilling commitments to improving women's reproductive health. l mdg . combat hiv/aids, malaria, tuberculosis, and other diseases -more people than ever are living with hiv owing to fewer aids-related deaths and the continued large number of new infections. in , an estimated . million were living with hiv, up percent from . this persistent increase reflects the continued large number of new infections along with a significant expansion of access to lifesaving antiretroviral therapy, especially in more recent years. l mdg . ensure environmental sustainability -the unparalleled success of the montreal protocol shows that action on climate change is within grasp. the th anniversary of the montreal protocol on substances that deplete the ozone layer, in , had many achievements to celebrate. most notably, there has been a reduction of over percent in the consumption of ozone-depleting substances. further, because most of these substances are also potent greenhouse gases, the montreal protocol has contributed significantly to the protection of the global climate system. the reductions achieved to date leave hydrochlorofluorocarbons (hcfcs) as the largest group of substances remaining to be phased out. l mdg . a global partnership for development -core development aid fell in real terms for the first time in more than a decade, as donor countries faced fiscal constraints. in , net aid disbursements amounted to $ . billion, representing . percent of developed countries' combined national income. while constituting an increase in absolute dollars, this was a . percent drop in real terms over . if debt relief and humanitarian aid are excluded, bilateral aid for development programmes and projects fell by . percent in real terms. equitable and sustainable funding of health services. . developing human resources (educational programs for providers and managers based on the principles of the health for all policy). . research and knowledge: health programs based on scientific evidence. . mobilizing partners for health (engaging the media/ television/internet). . policies and strategies for health for all -national, targeted policies based on health for all. a - review has been commissioned by the european office of the who to assess inequalities in the social determinants of health. while health has improved there are still significant inequalities. factors include variance in local, regional, national, and global economic forces. the european union and the european region of who are both working on health targets for the year . there are competing demands in society for expenditure by the government, and therefore making the best use of resources -money and people -is an important objective. the uk has devolved many of the responsibilities to the constituent countries (england, wales, scotland, and northern ireland) within an overall national framework (box . ). of the health consequences of their decisions and to accept responsibility for health. health promotion policy combines diverse but complementary approaches, including legislation, fiscal measures, taxation, and organizational change. it is a coordinated action that leads to health, income, and social policies that foster greater equity. joint action contributes to ensuring safer and healthier goods and services, healthier public services, and cleaner, more enjoyable environments. health promotion policies require the identification of obstacles to the adoption of healthy public policies in non-health sectors, and ways of removing them. built on progress made from the declaration on primary health care at alma-ata, the aim was to make the healthier choice the easier choice for policy makers as well. the logo of the ottawa charter has been maintained by the who as the symbol and logo of health promotion. health promotion represents activities to enhance and embed the concept of building healthy public policy through: l building healthy public policy in all sectors and levels of government and society l enhancing both self help and social support l developing personal skills through information and education for health l enabling, mediating, and advocating healthy public policy in all spheres l creating supportive environments of mutual help and conservation of the natural environment l reorienting health services beyond providing clinical curative services with linkage to broader social, political, economic, and physical environmental components. (adapted from ottawa charter; health and welfare canada and world health organization, ) an effective approach to health promotion was developed in australia where, in the state of victoria, revenue from a cigarette tax has been set aside for health promotion purposes. this has the effect of discouraging smoking, and at the same time finances health promotion activities and provides a focus for health advocacy in terms of promoting cessation of cigarette advertising at sports events or on television. it also allows for assistance to community groups and local authorities to develop health promotion activities at the workplace, in schools, and at places of recreation. health activity in the workplace involves reduction of work hazards as well as promotion of a healthy diet and physical fitness, and avoidance of risk factors such as smoking and alcohol abuse. in the australian model, health promotion is not only the persuasion of people to change their life habits; it also involves legislation and enforcement towards environmental changes that promote health. for example, this involves mandatory filtration, chlorination, and fluoridation for community water supplies, vitamin and mineral enrichment of basic foods. primary care alliances of service providers are organized including hospitals, community health services serving a sub-district population for more efficient and comprehensive care. these are at the level of national or state policy, and are vital to a health promotion program and local community action. community-based programs to reduce chronic disease using the concept of community-wide health promotion have developed in a wide variety of settings. such a program to reduce risk factors for cardiovascular disease was pioneered in the north karelia project in finland. this project was initiated as a result of pressures from the affected population of the province, which was aware of the high incidence of mortality from heart disease. finland had the highest rates of chd in the world and in the rural area of north karelia the rate was even higher than the national average. the project was a regional effort involving all levels of society, including official and voluntary organizations, to try to reduce risk factors for chd. after years of follow-up, there was a substantial decline in mortality with a similar decline in a neighboring province taken for comparison, although the decline began earlier in north karelia. in many areas where health promotion has been attempted as a strategy, community-wide activity has developed with participation of ngos or any valid community group as initiators or participants. healthy heart programs have developed widely with health fairs, sponsored by charitable or fraternal societies, schools, or church groups, to provide a focus for leadership in program development. a wider approach to addressing health problems in the community has developed into an international movement of "healthy cities". following deliberations of the health of towns commission chaired by edwin chadwick, the health of towns association was founded in by southwood smith, a prominent reform leader of the sanitary movement, to advocate change to reduce the terrible living conditions of much of the population of cities in the uk. the association established branches in many cities and promoted sanitary legislation and public awareness of the "sanitary idea" that overcrowding, inadequate sanitation, and absence of safe water and food created the conditions under which epidemic disease could thrive. in the s, iona kickbush, trevor hancock, and others promoted renewal of the idea that local authorities have a responsibility to build health issues into their planning and development processes. this "healthy cities" approach promotes urban community action on a broad front of health promotion issues (table . ). activities include environmental projects (such as recycling of waste products), improved recreational facilities for young people to reduce violence and drug abuse, health fairs to promote health awareness, and screening programs for hypertension, breast cancer, and other diseases. it combines health promotion with consumerism and returns to the tradition of local public health action and advocacy. the municipality, in conjunction with many ngos, develops a consultative process and program development approach to improving the physical and social life of the urban environment and the health of the population. in , the healthy cities movement involved countries with cities in europe, canada, the usa, the uk, south america, israel, and australia, an increase from cities in . the model now extends to small municipalities, often with populations of fewer than , . networks of healthy cities are the backbone of the movement, with more than member towns and cities across europe. the choice of core themes offers the opportunity to work on priority urban health issues that are relevant to all european cities. topics that are of particular concern to individual cities and/or are challenging and cutting edge for innovative public health action are especially emphasized. healthy cities encourages and supports experimentation with new ideas by developing concepts and implementing them in diverse organizational contexts. a healthy city is a city for all its citizens: inclusive, supportive, sensitive and responsive to their diverse needs and expectations. a healthy city provides conditions and opportunities that encourage, enable and support healthy lifestyles for people of all social groups and ages. a healthy city offers a physical and built environment that encourages, enables and supports health, recreation and well-being, safety, social interaction, accessibility and mobility, a sense of pride and cultural identity and is responsive to the needs of all its citizens. the apha's formulation of the public health role in , entitled the future of public health in america, was presented at the annual meeting in . the apha periodically revises standards and guidelines for organized public health services provided by federal, state, and local governments ( table . ). these reflect the profession of public health as envisioned in the usa where access to medical care is limited for large numbers of the population because of a lack of universal health insurance. public health in the usa has been very innovative in determining risk groups in need of special care and finding direct and indirect methods of meeting those needs. european countries such as finland have called for setting public health into all public policy, which reflects the vital role that local and county governments can play in developing health-oriented policies. these include policies in housing, recreation, regulation of industrial pollution, road safety, promotion of smoke-free environments, bicycle paths, health impact assessment, and many other applications of health principles in public policy. public health involves both direct and indirect approaches. direct measures in public health include immunization of children, modern birth control, and chronic disease case finding -hypertension, diabetes, and cancer. indirect methods used in public health protect the individual by community-wide means, such as raising standards of environmental safety, ensuring a safe water supply, sewage disposal, and improved nutrition (box . ). in public health practice, the direct and indirect pproaches are both relevant. to reduce morbidity and mortality from diarrheal diseases requires an adequate supply of safe water and waste disposal, and also education of the individual in hygiene and the mother in use of ort, and rotavirus vaccination of all children. the targets of public health action therefore include the individual, family, community, region, or nation, as well as a functioning and health system adopting current best practices for health care and health protection. the targets for protection in infectious disease control are both the individual and the total group at risk. for vaccine-preventable diseases, immunization protects the individual but also has an indirect effect by reducing the risk even for non-immunized persons. in control of some diseases, individual case finding and management reduce risk of the disease in others and the community. for example, tb requires case finding and adequate care among high-risk groups as a key to community control. in malaria control, case finding and treatment are essential together with environmental action to reduce the vector population, to prevent transmission of the organism by the mosquito to a new host. control of ncds, where there is no vaccine for mass application, depends on the knowledge, attitudes, beliefs, and practices of individuals at risk. in this case, the social context is of importance, as is the quality of care to which the individual has access. control and prevention of noninfectious diseases involve strategies using individual and population-based methods. individual or clinical measures include professional advice on how best to reduce the risk of the disease by early diagnosis and implementation of appropriate therapy. population-based measures involve indirect measures with government action banning cigarette advertising, or direct taxation on cigarettes. mandating food quality standards, such as limiting the fat content of meat, and requiring food labeling laws are part of the control of cardiovascular diseases. the way individuals act is central to the objective of reducing disease, because many non-infectious diseases are dependent on behavioral risk factors of the individual's choosing. changing the behavior of the individual means addressing the way a person sees his or her own needs. this can be influenced by the provision of information, but how someone sees his or her own needs is more complex than that. an individual may define needs differently from the society or the health system. reducing smoking among women may be difficult to achieve if smoking is thought to reduce appetite and food intake, given the social message that "slim is beautiful". reducing smoking among young people is similarly difficult if smoking is seen as fashionable and diseases such as lung cancer seem very remote. recognizing how individuals define needs helps the health system to design programs that influence behavior that is associated with disease. public health has become linked to wider issues as health care systems are reformed to take on both individual and population-based approaches. public health and mainstream medicine have found increasingly common ground in addressing the issues of chronic disease, growing attention to health promotion, and economics-driven health care reform. at the same time, the social ecology approaches have shown success in slowing major causes of disease, including heart disease and aids, and the biomedical sciences have provided major new technology for preventing major health problems, including cancer, heart disease, genetic disorders, and infectious diseases. technological innovations unheard of just a few years ago are now commonplace, in some cases driving up costs of care and in others replacing older and less effective care. at the same time, resistance of important pathogenic microorganisms to antibiotics and pesticides is producing new challenges from diseases once thought to be under control, and newly emerging infectious diseases challenge the entire health community. new generations of antibiotics, antidepressants, antihypertensive medications, and other treatment methods are changing the way many conditions are treated. research and development in the biomedical to improve the quality of public health practice and performance of public health systems sciences are providing means of prevention and treatment that profoundly affect disease patterns where they are effectively applied. the technological and organizational revolutions in health care are accompanied by many ethical, economic, and legal dilemmas. the choices in health care include heart transplantation, an expensive life-saving procedure, which may compete with provision of funds and labor resources for immunizations for poor children or for health promotion to reduce smoking and other risk factors for chronic disease. new means of detecting and treating acute conditions such as myocardial infarction and peptic ulcers are reducing hospital stays, and improving long-term survival and quality of life. imaging technology has been an important development in medicine since the advent of x-rays in the early twentieth century. technology has forged ahead with high-technology instruments and procedures, new medication, genetic engineering, and important low-technology gains such as impregnated bed nets, simplified tests for hiv and tb, and many other "game changers". new technologies that can enable lower cost diagnostic devices, electronic transmission, and distant reading of transmitted imaging all open up possibilities for advanced diagnostic capacities in rural and less developed countries and communities. molecular biology has provided methods of identifying and tracking movement of viruses such as polio and measles from place to place, greatly expanding the potential for appropriate intervention. the choices in resource allocation can be difficult. in part, these add political commitment to improve health, competent professionally trained public health personnel, the public's level of health information, and legal protection, whether through individuals, advocacy, or regulatory approaches for patients' rights. these are factors in a widening methodology of public health. the centers for disease control and prevention (morbidity and mortality weekly report) in summarized great achievements of public health in the usa, with an extension of the lifespan by over years and improvements in many measures of quality of life. they were updated in a similar summary report in , showing continuous progress, and a global version which was also encouraging in its scope of progress (table . ). these achievements were also seen in all developed countries over the past century and are beginning to be seen in developing countries as well. they reflect a successful application of a broad approach to prevention and health promotion along with improved medical care and growing access to its benefits. in the past several decades alone, major new innovations are leading to greater control of cardiovascular disease, cancer prevention, and many other improvements to health affecting hundreds of millions of people. a similar report by the cdc shows global progress in the first decade of the twenty-first century, while mdg reports show progress on all eight target topics, although not at uniformly satisfactory rates. these achievements are discussed throughout this text. this successful track record is very much at the center of a new public health involving a wide range of programs and activities, shown to be feasible and benefiting from continuing advances in science and understanding of social and management issues affecting health care systems worldwide. public health issues have received new recognition in recent years because of a number of factors, including a growing understanding among the populace at different levels in different countries that health behavior is a factor in health status and that public health is vital for protection against natural or human-made disasters. the challenges are also increasingly understood: preparation for bioterrorism, avian influenza, rising rates of diabetes and obesity, high mortality rates from cancer, and a wish for prevention to be effective. health systems offer general population benefits that go beyond preventing and treating illness. appropriately designed and managed, they: l provide a vehicle to improve people's lives, protecting them from the vulnerability of sickness, generating a sense of life security, and building common purpose within society l ensure that all population groups are included in the processes and benefits of socioeconomic development l generate the political support needed to sustain them over time. health systems promote health equity when their design and management specifically consider the circumstances and needs of socially disadvantaged and marginalized populations, including women, the poor, and groups who experience stigma and discrimination, enabling social action by these groups and the civil society organizations supporting them. health systems can, when appropriately designed and managed, contribute to achieving the millennium development goals. the mdgs selected by the un in have eight global targets for the year , including four directly related to public health (discussed above, box . ). these are a recognition and a challenge to the international community and public health as a profession and as organized systems. formal education in newly developing schools of public health is increasing in europe, including many countries of eastern europe, and beginning to develop in india and sub-saharan africa. but there is delay in establishing centers of postgraduate education and research in many developing countries which are concentrating their educational resources on training physicians. many physicians from developing nations are moving to the developed countries, which have become dependent on these countries for a significant part of their supply of medical doctors. progress in implementation of the mdgs is mixed in sub-saharan africa, making some progress in immunization, but falling back on other goals. proposals to renew global health targets following the end-stage of the mdg health goals will need to add a focus on ncds, which account for percent of global deaths, including . million premature deaths below the age of (undp). economic growth has been hampered by the global recession since , which will affect continued progress with many other factors of changing population dynamics, the economics of prevention versus expensive treatment costs, and the high costs of health care. environmental degradation with high levels of carbon dioxide contamination is a growing concern, with disastrous global warming and consequent effects of drought, flooding, hurricane, and elevated particulate matter-induced asthma and effects on cardiovascular disease. the potential for the development of basic and medical sciences in genetics, nanotechnology, and molecular biology shows enormous promise for health benefits as yet unimagined. at the same time, the effectiveness of health promotion has shown dramatic successes in reducing the toll of aids, reducing smoking, and increasing consciousness of nutrition and physical fitness in the population, and of the tragic effects of poverty and poor education on health status. the ethics of public health issues are complex and changing with awareness that failure to act on strong evidence-based policies is itself ethically problematic. the future of public health is not as a solo professional sector; it is at the heart of health systems, without which societies are open to chronic and infectious diseases that are preventable, affecting the society as a whole in economic and development matters. there is an expanding role of private donors in global health efforts, such as the rotary club and the polio eradication program, gavi with immunization and bed-nets in sub-saharan africa, and bilateral donor countries' help in reducing the toll of aids in sub-saharan africa. the new public health has emerged as a concept to meet a whole new set of conditions, associated with increasing longevity and aging of the population, with the post-world war ii baby-boom generation reaching the over- age group facing the growing importance of chronic diseases. inequalities in health exist in and between affluent and developing societies, as well as within countries, even those having advanced health care systems. regional inequalities are seen across the european region in an east-west gradient and globally a north-south divide of extremes of inequality. the global environmental and ecological degradation and pollution of air and water present grave challenges for developed and developing countries worldwide. yet optimism can be derived from proven track records of success in public health measures that have already been implemented. many of the underlying factors are amenable to prevention through social, environmental, or behavioral change and effective use of medical care. the new public health idea has evolved since alma-ata, which articulated the concept of health for all, followed by a trend in the late s to health in all policies and establishing health targets as a basis for health planning. during the late s and early s, the debate on the future of public health in the americas intensified as health professionals looked for new models and approaches to public health research, training, and practice. this debate helped to redefine traditional approaches of social, community, and preventive medicine. the search for the "new" in public health continued with a return to the health for all concept of alma-ata (renewed in ) and a growing realization that the health of both the individual and the society involves the management of personal care services and community prevention, with a comprehensive approach taking advantage of advancing technology and experience of best practices globally. the new public health is an extension of the traditional public health. it describes organized efforts of society to develop healthy public policies: to promote health, to prevent disease, and to foster social equity within a framework of sustainable development. a new, revitalized public health must continue to fulfill the traditional functions of sanitation, protection, and related regulatory activities, but in addition to its expanded functions. it is a widened philosophy and practical application of many different methods of addressing health, and preventing disease and avoidable death. it necessarily addresses inequities so that programs need to meet special needs of different groups in the population according to best standards, limited resources, and population needs. it is proactive and advocates interventions within legal and ethical limits to promote health as a value in and of itself and as an economic gain for society as well for its individual members. the new public health is a comprehensive approach to protecting and promoting the health status of the individual and the society, based on a balance of sanitary, environmental, health promotion, personal, and community-oriented preventive services, coordinated with a wide range of curative, rehabilitative, and long-term care services. it evolves with new science, technology, and knowledge of human and systems behavior to maximize health gains for the individual and the population. the new public health requires an organized context of national, regional, and local governmental and non-governmental programs with the object of creating healthful social, nutritional, and physical environmental conditions. the content, quality, organization, and management of component services and programs are all vital to its successful implementation. whether managed in a diffused or centralized structure, the new public health requires a systems approach acting towards achievement of defined objectives and specified targets. the new public health works through many channels to promote better health. these include all levels of government and parallel ministries; groups promoting advocacy, academic, professional, and consumer interests; private and public enterprises; insurance, pharmaceutical, and medical products industries; the farming and food industries; media, entertainment, and sports industries; legislative and law enforcement agencies; and others. the new public health is based on responsibility and accountability for defined populations in which financial systems promote achievement of these targets through effective and efficient management, and cost-effective use of financial, human, and other resources. it requires continuous monitoring of epidemiological, economic, and social aspects of health status as an integral part of the process of management, evaluation, and planning for improved health. the new public health provides a framework for industrialized and developing countries, as well as countries in political-economic transition such as those of the former soviet system. they are at different stages of economic, epidemiological, and sociopolitical development, each attempting to ensure adequate health for its population with limited resources. the challenges are many, and affect all countries with differing balances, but there is a common need to seek better survival and quality of life for their citizens (table . ). the object of public health, like that of clinical medicine, is better health for the individual and for society. public health works to achieve this through indirect methods, such as by improving the environment, or through direct means such as preventive care for mothers and infants or other atrisk groups. clinical care focuses directly on the individual patient, mostly at the time of illness. but the health of the individual depends on the health promotion and social programs of the society, just as the well-being of a society depends on the health of its citizens. the new public health consists of a wide range of programs and activities that link individual and societal health. the "old" public health was concerned largely with the consequences of unhealthy settlements and with safety of food, air, and water. it also targeted the infectious, toxic, and traumatic causes of death, which predominated among young people and were associated with poverty. a summary of the great achievements of public health in the twentieth and in the early twenty-first century in the industrialized world is included in chapter and throughout this text. these achievements are reflective of public health gains throughout the industrialized world and are encourage and leverage national, state, and local partnerships to build a stronger foundation for public health preparedness and investigate health problems and health hazards in the community . inform, educate, and empower people about health issues . mobilize community partnerships to identify and solve health problems . develop policies and plans that support individual and community health efforts . enforce laws and regulations that protect health and ensure safety evaluate effectiveness, accessibility, and quality of personal and population-based health services vision, mission and goals guidelines on food fortification with micronutrients. who, geneva. alliance for health policy and systems research essential public health services healthy communities, . model standards for community attainment of the year national health objectives determinants of adult mortality in russia: estimates from sibling data commission on social determinants and health. closing the gap in a generation: health equity through action on the social determinants of health compression of morbidity in the elderly institute of medicine. who will keep the public healthy? educating public health professionals for the st century global alliance for vaccine and immunization (gavi) chronic disease prevention and the new public health the evolution, impact and significance of healthy cities/healthy communities world health organization. ottawa charter for health promotion: an international conference on health promotion behavioral and social sciences and public health at cdc. mmwr health in all policies: seizing opportunities, implementing policies. ministry of social affairs and health new perspectives on the health of canadians: a working document new perspective on the health of canadians: years later the us healthy people initiative: its genesis and its sustainability mortality from cardiovascular and cerebrovascular diseases in europe and other areas of the world: an update strategic review of health inequalities in england post. department of health primary care (extended version): ten key actions could globally ensure a basic human right at almost unnoticeable cost public health in europe: power, politics, and where next health: a vital investment for economic development in eastern europe and central asia. european observatory on health systems and policies. who, european regional office it is not just the broad street pump addressing the epidemiologic transition in the former soviet union: strategies for health systems and public health reform in russia what is the "new public health"? millenium development goals: progress chart united nations development programme, millennium development goals. eight goals for healthy people healthy people. the surgeon general's report on health promotion and disease prevention the millennium development goals: a cross-sectoral analysis and principles for goal-setting after selective primary health care: an interim strategy for disease control in developing countries declaration of alma-ata. international conference on primary health care healthy cities networks across the who, european region preamble to the constitution of the world health organization as adopted by the international health conference regional office for europe. health -health for all in the st century. who regional office for europe, copenhagen. world health organization, . regional office for europe. who european healthy cities network. available at:. who regional office for europe leading health indicators selected for incorporate the original objectives in healthy people , which served as a basis for planning public health activities for many state and community health initiatives. for each of the leading health indicators, specific objectives and subobjectives derived from healthy people are used to monitor progress. the specific objectives set for healthy people are listed in box . . thirteen new topic areas are listed for , such as older adults, genomics, dementias, and social determinants of health. these provide guidelines for national, state, and local public health agencies as well as insurance providers, primary care services, and health promotion advocates. a key issue will be in reducing regional, ethnic, and socioeconomic health disparities.the process of working towards health targets in the usa has moved down from the federal level of government to the state and local levels. professional organizations, ngos, as well as community and fraternal organizations are also involved. the states are encouraged to prepare their own targets and implementation plans as a condition for federal grants, and many states require county health departments to prepare local profiles and targets.diffusion of this approach encourages state and local initiatives to meet measurable program targets. it also sets a different agenda for local prestige in competitive terms, with less emphasis on the size of the local hospital or other agencies than on having the lowest infant mortality or the least infectious disease among neighboring local authorities. the who european region document "health -health for all in the st century" addresses health in the twentyfirst century, with principles and objectives for improving the health of europeans, within and between countries of europe. the health targets include: . closing the health gap between countries. . closing the health gap within countries. . a healthy start in life (supportive family policies). . health of young people (policies to reduce child abuse, accidents, drug use, and unwanted pregnancies). . healthy aging (policies to improve health, self-esteem, and independence before dependence emerges). . improving mental health. . reducing communicable diseases. . reducing non-communicable diseases. . reducing injury from violence and accidents. . a healthy and safe physical environment. . healthier living (fiscal, agricultural, and retail policies that increase the availability of and access to and consumption of vegetables and fruits). . reducing harm from alcohol, drugs, and tobacco. . a settings approach to health action (homes should be designed and built in a manner conducive to sustainable health and the environment). . multisectoral responsibility for health. . an integrated health sector and much stronger emphasis on primary care. . managing for quality of care using the european health for all indicators to focus on outcomes and compare the effectiveness of different inputs. the uk national health service (nhs) has semi-autonomous units in england, scotland, wales, and northern ireland. they are funded from the central uk nhs but with autonomy within national guidelines. the nhs has defined national health outcomes for improvements grouped around five domains, each comprised of key indicators aimed at improving health with reducing inequalities. l preventing people from dying prematurely from causes amenable to health care for all ages: l the target diseases include cardiovascular, respiratory, and liver diseases, and cancer (with focus on cancer of breast, lung, and colorectal cancer) l reducing premature death in people with serious mental illnesses l reducing infant mortality, neonatal mortality, still births, and deaths in young children l increasing -year survival for children with cancer. health improvement; help people to live healthy lifestyles, healthy choices, reduce health inequalities, protection from major incidents and other threats, while reducing health inequalities. l health care, public health and preventing premature mortality; reduce the numbers of people living with preventable ill-health and people dying prematurely, while reducing the gap between communities.source: uk department of health. available at: https://www.gov.uk/government/organisations/department-of-health/about#our-priorities, https:// www.gov.uk/government/uploads/system/uploads/attachment_data/ file/ /improving-outcomes-and -supporting-transparency-part- a.pdf. pdf, and https://www.gov.uk/government/uploads/system/uploads/attach-ment_data/file/ / -nhs-outcomes-framework- - .pdf. pdf [accessed june ] . national policy in health ultimately relates to health of the individual. the various concepts outlined in the health field concept, community-oriented primary health care, health targets, and effective management of health systems, can only be effective if the individual and his or her community are knowledgeable participants in seeking solutions. involving the individual in his or her own health status requires raising levels of awareness, knowledge, and action. the methods used to achieve these goals include health counseling, health education, and health promotion (figure . ).health counseling has always been a part of health care between the doctor or nurse and the patient. it raises levels of awareness of health issues of the individual patient. health education has long been part of public health, dealing with promoting consciousness of health issues in selected target population groups. health promotion incorporates the work of health education but takes health issues to the policy level of government and involves all levels of government and ngos in a more comprehensive approach to a healthier environment and personal lifestyles.health counseling, health education, and health promotion are among the most cost-effective interventions for improving the health of the public. while costs of health care are rising rapidly, demands to control cost increases should lead to greater emphasis on prevention, and adoption of health education and promotion as an integral part of modern life. this should be carried out in schools, the workplace, the community, commercial locations (e.g., shopping centers), and recreation centers, and in the political agenda.psychologist abraham maslow described a hierarchy of needs of human beings. every human has basic requirements including physiological needs of safety, water, food, warmth, and shelter. higher levels of needs include recognition, community, and self-fulfillment. these insights supported observations of efficiency studies such as those of elton mayo in the famous hawthorne effect in the s, showing that workers increased productivity when acknowledged by management in the objectives of the organization (see chapter ). in health terms, these translate into factors that motivate people to positive health activities when all barriers to health care are reduced.modern public health faces the problem of motivating people to change behavior; sometimes this requires legislation, enforcement, and penalties for failure to comply, such as in mandating car seat-belt use. in other circumstances it requires sustained performance by the individual, such as the use of condoms to reduce the risk of sti and/or hiv transmission. over time, this has been developed into a concept known as knowledge, attitudes, beliefs, and practices (kabp), a measurable complex that cumulatively affects health behavior (see chapter ). there is often a divergence between knowledge and practice; for example, the knowledge of the importance of safe driving, yet not putting this into practice. this concept is sometimes referred to as the "kabp gap". the health belief model has been a basis for health education programs, whereby a person's readiness to take action for health stems from a perceived threat of disease, a recognition of susceptibility to disease and its potential severity, and the value of health. action by an individual may be triggered by concern and by knowledge. barriers to appropriate action may be psychological, financial, or physical, including fear, time loss, and inconvenience. spurring action to avoid risk to health is one of the fundamental goals in modern health care. the health belief model is important in defining any health intervention in that it addresses the emotional, intellectual, and other barriers to taking steps to prevent or treat disease.health awareness at the community and individual levels depends on basic education levels. mothers in developing countries with primary or secondary school education are more successful in infant and child care than less educated women. agricultural and health extension services reaching out to poor and uneducated farm families in north america in the s were able to raise consciousness of safe self-health practices and good nutrition, and when this was supplemented by basic health education in schools, generational differences could be seen in levels of awareness of the importance of balanced nutrition. secondary prevention with diabetics and patients with chd hinges on education and awareness of nutritional and physical activity patterns needed to prevent or delay a subsequent myocardial infarction. the who sponsored the first international conference on health promotion held in ottawa, canada, in ( figure . ) . the resulting ottawa charter defined health promotion and set out five key areas of action: building healthy public policy, creating supportive environments, strengthening community action, developing personal skills, and reorienting health services. the ottawa charter called on all countries to put health on the agenda of policy makers in all sectors and at all levels, directing them to be aware a typical healthy city has a population in the multiple thousands, often multilingual, with an average middleclass income. a healthy cities project builds a coalition of municipal and voluntary groups working together in a continuing effort to improve quality of service, facilities, and living environment. the city is divided into neighborhoods, engaged in a wide range of activities fostered by the project. municipalities have traditionally had a leading role in sanitation, safe water supply, building and zoning laws and regulation, and many other responsibilities in public health (see chapter ). the healthy cities or communities movement has elevated this to a higher level with policies to promote health in all actions. some examples are listed of municipal, advocacy group, and higher governmental activities for healthier city environments: working with senior levels of government, other departments in the municipalities, religious organizations, private donors, and the ngo sector to innovate and especially to improve conditions in poverty-afflicted areas of cities is a vital role for health-oriented local political leadership. human ecology, a term introduced in the s and revived in the s, attempted to apply theory from plant and animal life to human communities. it evolved as a branch of demography, sociology, and anthropology, addressing the social and cultural contexts of disease, health risks, and human behavior. human ecology addresses the interaction of humans with and adaptation to their social and physical environment.parallel subdisciplines of social, community, and environmental psychology, medical sociology, anthropology, and other social sciences contributed to the development of this academic field with wide applications in health-related issues. this led to the incorporation of qualitative research methods alongside the quantitative research methods traditionally emphasized in public health, providing crucial insights into many public health issues where human behavior is a key risk factor.health education developed as a discipline and function within public health systems in school health, rural nutrition, military medicine, occupational health, and many other aspects of preventive-oriented health care, and is discussed in later chapters of this text. directed at behavior modification through information and raising awareness of consequences of risk behavior, this has become a longstanding and major element of public health practice in recent times, being almost the only effective tool to fight the epidemic of hiv and the rising epidemic of obesity and diabetes.health promotion as an idea evolved, in part, from marc lalonde's health field concepts and from growing realization in the s that access to medical care was necessary but not sufficient to improve the health of a population. the integration of the health behavior model, social ecological approach, environmental enhancement, or social engineering formed the basis of the social ecology approach to defining and addressing health issues (table . ).individual behavior depends on many surrounding factors, while community health also relies on the individual; the two cannot be isolated from one another. the ecological perspective in health promotion works towards changing people's behavior to enhance health. it takes into account factors not related to individual behavior, which are determined by the political, social, and economic environment. it applies broad community, regional, or national approaches that are needed to address severe public health problems, such as controlling hiv infection, tb, malnutrition, stis, cardiovascular disorders, violence and trauma, and cancer. beginning to affect the health situation in countries in transition from the socialist period. countries emerging from developing status are also showing signs of mixed progress in the dual burden of infectious and maternal/child health issues, along with growing exposure to the chronic diseases of developed nations such as cardiovascular diseases, obesity, and diabetes. the new public health synthesizes traditional pub lic health with management of personal services and community action for a holistic approach. evaluation of costeffective public health and medical interventions to reduce the burden of disease also contributes to the need to seek and apply new approaches to health. the new public health will continue to evolve as a framework drawing on new ideas, science, technology, and experiences in public health throughout the world. it must address the growing recognition of social inequality in health, even in developed countries with universal health programs with improved education and social support systems. for a complete bibliography and guidance for student reviews and expected competencies please see companion web site at http://booksite.elsevier.com/ bibliography key: cord- -ri dy e authors: more, gd; dunowska, m; acke, e; cave, nj title: a serological survey of canine respiratory coronavirus in new zealand date: - - journal: n z vet j doi: . / . . sha: doc_id: cord_uid: ri dy e aims: to determine the seroprevalence of canine respiratory coronavirus (crcov) in new zealand dogs, and to explore associations with age, sex, breed, month, and geographical region of sampling and reported presence of clinical signs suggestive of respiratory disease. methods: a total of , canine serum samples were randomly selected from submissions to a diagnostic laboratory between march and december , and were analysed for crcov antibodies using a competitive elisa. logistic regression analysis was used to determine associations between seroprevalence of crcov and breed category, age, sex, sampling month, region, and reported health status of dogs. results: overall, / , ( . %) samples were seropositive for crcov, with / ( . %) positive dogs in the north island and / ( %) in the south island. age of dog, sampling month, region, and presence of abnormal respiratory signs were included in the initial logistic regression model. seroprevalence was higher in dogs aged ≥ compared with ≤ years (p < . ). the lowest seroprevalence was observed in july ( / ; . %) and august ( / ; %), and the highest in june ( / ; %). seroprevalence in dogs from auckland was higher than in dogs from the hawkes bay, manawatu, marlborough, and waikato regions (p < . ). abnormal respiratory signs (coughing, nasal discharge, or sneezing) were reported for / , ( . %) dogs sampled. seroprevalence for crcov tended to be higher among dogs with respiratory signs ( . ( % ci = . – . )%) than dogs with no reported respiratory signs ( . ( % ci = . – . )%). conclusions: serological evidence of infection with crcov was present in more than half of the dogs tested from throughout new zealand. differences in crcov seroprevalence between regions and lack of seasonal pattern indicate that factors other than external temperatures may be important in the epidemiology of crcov in new zealand. clinical relevance: our data suggest that crcov should be included in investigations of cases of infectious canine tracheobronchitis, particularly if these occur among dogs vaccinated with current vaccines, which do not include crcov antigens. canine respiratory coronavirus (crcov) is a large enveloped rna virus that is classified within a species betacoronavirus in the family coronaviridae (erles et al. ) . the virus was first isolated from dogs with respiratory disease in a rehoming shelter in the united kingdom (erles et al. ) . on the day of admission to that shelter % of dogs were seropositive, and nearly all seronegative dogs seroconverted to crcov after a -week stay at the shelter, indicating high transmissibility of the virus. the presence of crcov antibody on entry to the shelter was associated with decreased risk of development of respiratory disease, suggesting an aetiological involvement of the virus in infectious canine tracheobronchitis (ict). results of several further studies in the united kingdom and other countries also suggested that crcov contributes to development of respiratory disease in infected dogs (erles and brownlie ; ellis et al. ; kaneshima et al. ) . however affected dogs were often coinfected with several respiratory pathogens, and not all dogs with serological evidence of recent crcov infection developed respiratory disease, making the establishment of an aetiological link between crcov infection and disease challenging (erles et al. ; erles and brownlie ) . this is similar to the situation observed for other respiratory pathogens of dogs, underscoring the fact that the aetiology of ict is complex and factors other than exposure to a specific pathogen are likely to contribute to the outcome of infection (erles and brownlie ; mitchell et al. ) . canine respiratory coronavirus is closely related to bovine coronavirus (bcov) and human coronavirus-oc , but distinct from canine enteric coronavirus (cecov) , which belongs to the genus alphacoronavirus, and is an aetiological agent of enteric disease in dogs (erles et al. ; decaro et al. ) . antibodies raised to crcov are not cross-reactive with cecov (decaro et al. ; priestnall et al. ) . similarly, vaccines against cecov do not elicit protection against crcov infection (erles and brownlie ) . a high percentage identity was found between the amino acid sequence of the spike protein of bcov and crcov (erles et al. ) , enabling the use of bcov antigens for the detection of crcov antibody (priestnall et al. ; decaro et al. ; soma et al. ) . there are limited data on crcov epidemiology in new zealand. based on a single cross-sectional survey of dogs, knesl et al. ( ) reported that ( %) dogs were seropositive for crcov. in another new zealand-based study, / ( %) dogs sampled had antibody to crcov (sowman et al. ) . some of the dogs affected by ict seroconverted to crcov between acute and convalescent sampling, suggesting that crcov infection was associated with the development of disease in those dogs. however there was a poor match between diseased and healthy dogs in terms of age, breed, and use, so no conclusions could be made regarding aetiological involvement of crcov in development of ict (sowman et al. ) . the aim of the present study was to investigate the epidemiology of crcov in a large sample of dogs in new zealand, to explore the associations between seroprevalence for crcov and age, sex, breed, month, and geographical region of sampling, as well as the reported presence of clinical signs suggestive of respiratory disease. a convenience sample of canine sera was obtained from a commercial veterinary laboratory (new zealand veterinary pathology ltd., palmerston north, nz) on a monthly basis. approximately serum samples, representing % of monthly laboratory submissions, were randomly selected every month from march to december . this was done by physically pulling samples out of a bag containing all monthly laboratory submissions and checking these against an excel database containing available data for each sample. only those samples with information on sex, age, the region of sampling, and clinical history were included in the study. samples having incomplete information and duplicate sera having the same label numbers were excluded. in addition, samples collected from racing greyhounds that were sent directly to our laboratory were also included in the study. four were from dogs with respiratory disease and from healthy dogs. dogs were categorised as healthy or sick based on the information provided on the submission form. healthy dogs included those presented for procedures such as pre-anaesthetic work-up or pre-mating progesterone concentrations, while sick dogs included those presented for a variety of infectious or non-infectious diseases. the serum samples were also categorised into those that came from dogs for which no abnormal respiratory signs were listed on the submission form, and those for which at least one of the clinical signs commonly associated with respiratory disease (coughing, sneezing, or nasal discharge) was listed. sera were stored at − °c until assayed. presence of crcov antibody in canine sera was determined using a commercially available competitive elisa with bcov antigen (bio k -monoscreen abelisa bovine coronavirus/competition, bio-x diagnostics, rochefort, belgium). the test was performed according to the manufacturer's instructions using provided positive and negative controls. the results were calculated based on the optical density at nm (od ) and presented as percentage of inhibition (poi) according to the formula: the manufacturer's recommended cut-offs for bcov antibody were used. accordingly, samples with poi ≥ % were considered positive for crcov antibody. based on the results of the elisa samples were categorised as seropositive or seronegative and this was the dependent variable for analyses. independent variables included the dog-related variables of age (≤ , - , - , ≥ years), sex (female/male), breed group (pet dogs, working dogs, non-descript dogs), health status (healthy/not healthy), and presence of respiratory signs (yes/no), as well as the samplingrelated variables of month of sampling (march to december ) and geographical region (auckland, hawkes bay, manawatu, marlborough/canterbury, nelson/tasman, northland, otago, taranaki, waikato, wellington). for some analyses, geographical regions were categorised as south island and north island. there were dog breeds which were categorised as working dogs (huntaway, heading dogs, and greyhounds), pet dogs which included all other recognised breeds, and non-descript dogs which included unspecified breeds. associations between seroprevalence and categorical variables were initially examined using a two-tailed pearson's χ or kruskal-wallis tests. those variables that were associated (p ≤ . ) were included in a multivariable model, which was refined by a stepwise backwards selection process retaining variables with p ≤ . . the mean poi for dogs of different age categories or health status were compared using one-way anova and tukey's test. all statistical analyses were performed using r statistical software v . . (r development core team, ; r foundation for statistical computing, vienna, austria) or graphpad prism (version . , graphpad software, san diego, ca, usa). samples were analysed from a total of , dogs. the median age of dogs was years (min week, max years), and there were similar numbers of male and female dogs ( table ). the origin of the samples by geographical region is shown in figure : / , ( . %) were submitted from the north island and / , ( . %) from the south island. overall, / , ( . %) samples were seropositive for crcov, with / ( . %) positive dogs in the north island and / ( %) in the south island. the seroprevalence of crcov among dogs classified as healthy ( / ; . ( % ci = . - . )%) was similar to that among dogs classified as diseased ( / ; . ( % ci = . - . )%, p = . ). univariate analyses revealed associations between samples seropositive for crcov and sampling month, age, and geographical region (p < . ). no statistical association was found between crcov seroprevalence and health status, breed, or gender of the dogs sampled (p > . ). four variables satisfied the criteria for inclusion in the initial multivariable model (p ≤ . ), namely age, sampling month, region, and presence of abnormal respiratory signs (table ) . age, sampling month, and region were retained in the final model (p ≤ . ). seroprevalence for crcov was higher in dogs aged ≥ compared with ≤ years (p < . ), but mean poi in seropositive dogs was lower in older than in younger dogs ( figure ). abnormal respiratory signs (coughing, nasal discharge, or sneezing) were reported for only / , ( . %) dogs sampled. seroprevalence for crcov tended to be higher among dogs with respiratory signs ( . ( % ci = . - . )%) than dogs with no reported respiratory signs ( . ( % ci = . - . )%). in addition, seropositive dogs with abnormal respiratory signs (n = ) tended to have higher mean poi ( . ( % ci = . - . )%) compared to all other seropositive dogs (n = ) ( . ( % ci = . - . )%, p = . ), but mean poi was similar to that of seropositive healthy dogs (n = ) ( . ( % ci = . - . )%, p = . ). the results of this study provided evidence that infection with crcov was common among dogs in new zealand. overall, % of the sera tested were positive for crcov antibodies. this was higher than the % reported previously in new zealand (knesl et al. ). both studies used sera submitted to the same diagnostic laboratory as the source of diagnostic material. however in the study samples were tested in comparison to , in the current study. hence, the current estimation of crcov seroprevalence may be more accurate than the previous one. the population sampled in the study was somewhat loosely defined as representing a wide geographic area encompassing the central and lower north island of new zealand. although samples in the current study originated from a wider geographical area, including the south island, the majority of samples were from the central and lower north island, so of similar distribution to the previous study. the difference in seroprevalence is also unlikely to be attributed to differences in the serological tests used, as the sensitivity and specificity of bcov-based competitive elisa for detection of crcov antibody was reported to be . % and . %, respectively, when compared to a fluorescent antibody test with crcov antigen that was used in the previous study (priestnall et al. ) . the timing of sample collection may have contributed to the differences observed between the two studies. unfortunately, the timing of sample collection was not provided by knesl et al. ( ) , but in the current study the lowest seroprevalences were observed in july ( %) and august ( %), which were similar to the % reported by knesl et al. ( ) . this may also be supported by the fact that % of dogs tested as part of another new zealand-based survey were seropositive for crcov (sowman et al. ) . the number of samples tested in that study was only , but, as in the current study, the samples were collected over a period of several months from july to august . finally, we cannot exclude the possibility that the seroprevalence of crcov has increased in new zealand since . as measured by a blocking elisa using bovine coronavirus as antigen, in serum samples from dogs that were seropositive for crcov and aged ≤ (n = ), - (n = ), - (n = ) or ≥ (n = ) years. the median is indicated by the middle line of each box, the mean by a cross, the th and th percentiles are indicated by the upper and lower edges of the boxes and minimum and maximum values are indicated by the whiskers. the significance of differences are indicated by * (p < . ) and ** (p < . ). the new zealand data appear to be similar to the seroprevalence of crcov reported from other countries, including . % in canada, . % in the united states of america, % in the united kingdom, and . % in the republic of ireland (priestnall et al. ) , as well % reported from a multicentre study that included dogs from six european countries sampled over a period of years (mitchell et al. ) . similar to our results, other studies found regional differences in crcov seroprevalence, as can be exemplified by differences between various regions in the united states of america and in the united kingdom. it has been suggested that the crcov seroprevalence may be higher in areas with a higher density of humans, and therefore presumably canine, populations (priestnall et al. ). however crcov seroprevalence was similar in some of the less densely populated regions of the south island and the more densely populated region of auckland. on the other hand, regional differences were apparent, as seroprevalence in dogs from auckland was higher in comparison to dogs from the hawkes bay, manawatu, marlborough, and waikato regions. one possible reason for these differences is sample size and associated selection bias. in addition, population density in most parts of new zealand, possibly with the exception of auckland, is not uniform. hence it may have been of interest to stratify the samples by the size of town/city, in addition to the geographical region. this was not performed as we did not have access to addresses of the submitters beyond the region classification. overall, our data suggest that the epidemiology of crcov in new zealand is similar to that observed overseas, particularly in europe and in the united states of america. the crcov seroprevalence varied between different months, but there was no clear seasonal pattern observed. the lowest crcov seroprevalences ( % and %) were detected in the winter months of july and august, but the highest seroprevalence ( %) was also observed in winter (june). this suggests that temporal differences in crcov seroprevalence were more likely to be related to factors other than external temperatures. these could include the increased contact between infected and non-infected dogs through activities such as training, competitions, short-or long-term kennelling or travel, but the exact nature of such interactions and their influence on the spread of crcov remain to be elucidated. similarly to results from other surveys (priestnall et al. (priestnall et al. , knesl et al. ), the seroprevalence of crcov was higher in dogs aged ≥ compared with ≤ years. this is most easily explained by the increased likelihood of exposure to the virus for older dogs, which had more opportunities for contact with infectious dogs or contaminated environments than younger dogs. however we did not see a relative decline in the percentage of seropositive dogs among those older than years, as reported by priestnall et al. ( priestnall et al. ( , . those authors suggested that this could be related to the age-related fall in the efficiency of the immune response. in the current study, mean poi was lowest in seropositive dogs > years of age, which may support this conclusion. as it is currently unknown how long crcov antibodies persist in dogs, the lower poi detected in older dogs may also represent residual antibody due to past exposure as opposed to recent infection. no statistically significant difference was observed between the seroprevalence of crcov in healthy and sick dogs, although seroprevalence tended to be higher in dogs with abnormal respiratory signs compared to those with no reported respiratory signs. while this is consistent with the overseas data (erles et al. ; soma et al. ) , the number of dogs with respiratory signs in the current study was low, and thus these dogs were poorly matched to either healthy dogs or dogs with clinical problems other than respiratory disease. in addition, some dogs categorised as having abnormal respiratory signs may have been included due to non-infectious causes, as the group allocation was made based on limited clinical data provided on the submission form. finally, the retrospective nature of the study, combined with the samples being sourced from a diagnostic laboratory, was likely to introduce a selection bias towards dogs with a variety of health problems compared with the general population. hence field studies using similarly sized, age-matched groups of dogs with and without respiratory disease would be needed to further investigate the impact of crcov infection on the health status of affected dogs. the sampled population contained different dog breeds making the analysis of breed associations with seroprevalence of crcov impractical. therefore breeds were categorised into broad use categories instead. this may have introduced some confounding as it is possible that some dogs of breeds that are typically used as farm working dogs may have been kept as pet dogs, while some dogs that were classified as pets based on their breeds may have been used as working dogs. none-the-less, there appeared to be no difference in seroprevalence of crcov among dogs from different use categories, which was consistent with results of an et al. ( ) who reported no difference in crcov seroprevalence between farm dogs and pet dogs. also consistent with overseas findings (erles and brownlie ; soma et al. ) was the lack of association between the sex of the dog and seroprevalence of crcov, indicating that sex-related activities or behaviours are unlikely to be associated with the likelihood of exposure to the virus. in conclusion, we have shown serological evidence that more than half of the dogs tested from throughout new zealand were infected with crcov at some point during their lives. further studies into the virus-host interactions and the impact of crcov infection on the health status of dogs under local new zealand conditions are warranted. the importance of crcov in ict remains to be elucidated. however, considering the apparent high seroprevalence of crcov in new zealand, this virus should be included in investigations of cases of ict, particularly if these occur among dogs vaccinated with current vaccines, which do not include crcov antigens. a serological survey of canine respiratory coronavirus and canine influenza virus in korean dogs serological and molecular evidence that canine respiratory coronavirus is circulating in italy detection of coronavirus in cases of tracheobronchitis in dogs: a retrospective study from to detection of a group coronavirus in dogs with canine infectious respiratory disease investigation into the causes of canine infectious respiratory disease: antibody responses to canine respiratory coronavirus and canine herpesvirus in two kennelled dog populations canine respiratory coronavirus: an emerging pathogen in the canine infectious respiratory disease complex the prevalence of a group coronavirus in dogs in japan the seroprevalence of canine respiratory coronavirus and canine influenza virus in dogs in new zealand european surveillance of emerging pathogens associated with canine infectious respiratory disease serological prevalence of canine respiratory coronavirus serological prevalence of canine respiratory coronavirus in southern italy and epidemiological relationship with canine enteric coronavirus prevalence of antibodies to canine respiratory coronavirus in some dog populations in japan a survey of canine respiratory pathogens in new zealand dogs sincere thanks to raewynne pearson and adrienne french for supplying the serum samples for elisa and to janis bridges for help with statistical analysis. this study was partly funded by the new zealand greyhound racing association. key: cord- - uiv n authors: nori, priya; szymczak, wendy; puius, yoram; sharma, anjali; cowman, kelsie; gialanella, philip; fleischner, zachary; corpuz, marilou; torres-isasiga, julian; bartash, rachel; felsen, uriel; chen, victor; guo, yi title: emerging co-pathogens: new delhi metallo-beta-lactamase producing enterobacterales infections in new york city covid- patients date: - - journal: int j antimicrob agents doi: . /j.ijantimicag. . sha: doc_id: cord_uid: uiv n • critically-ill covid- patients with new delhi metallo-beta-lactamase producing enterobacterales infections at our medical center had poor outcomes, including death in of cases; • multiple insults contributed to the occurrence of co-infection in these patients, including prolonged hospitalization, intubation, invasive devices, extensive antibiotic use, immunosuppressive therapy and environmental factors; • there are few antibiotic options for treatment of infections with new delhi metallo-beta-lactamase producing enterobacterales, contributing to poor outcomes; • hospitals and public health authorities should be vigilant for extensively drug resistant bacterial co-infections in patients hospitalized with covid- . four of five patients succumbed to septic shock due to advanced covid- , polymicrobial infection, or both. average length of hospitalization prior to death (n = ) or discharge (n = ) was . days. since , ndm has been increasingly reported in us patients without international healthcare exposure ( ). healthcare-associated ndm- e. cloacae outbreaks characterized using whole genome sequencing demonstrated persistence of resistant strains for over two years, despite rigorous control measures ( ) . screening for colonization without specific epidemiologic risk factors is not universally performed ( ). antimicrobial stewardship programs have a crucial role in limiting excess antibiotic use and providing expertise on extensively drug-resistant infections, however, treatment of class b mbls remains challenging. new β-lactamase inhibitors only have activity against ambler class a and d serine β-lactamases but not mbls ( ) . the presence of co-existing resistance mechanisms leave few therapeutic options. polymyxins are limited by unfavorable side effects, emerging resistance and poor outcomes ( ) . tigecycline has limited in-vivo efficacy for severe infections and benefits of higher dosing remains unclear ( ) . certain ndm-producing isolates also possess s rrna methylases, rendering aminoglycosides ineffective ( ) the combination of aztreonam and ceftazidime-avibactam has theoretic activity against ndmproducing enterobacterales. aztreonam is not hydrolyzed by mbls but its use is limited by coexisting serine β-lactamases ( ) avibactam has no activity against mbls but may protect in conclusion, hospitals should conduct close monitoring for excess antibiotic use and digression from infection prevention bundles during the covid- pandemic to prevent emergence of extensively drug resistant infections with limited antibiotic options. intensified commitment to new drug development is urgently needed as part of pandemic planning. coordinated hospital and public health antimicrobial resistance surveillance will be required for many years post covid- . funding: no funding source bacterial and fungal infections in covid- patients: a matter of concern covid- and the potential long-term impact on antimicrobial resistance preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease -united states new delhi metallo-β-lactamase and multidrug resistance: a global sos? investigation of a hospital enterobacter cloacae ndm- outbreak using whole genome sequencing. access microbiology ndm metallo-β-lactamases and their bacterial producers in health care settings infections caused by carbapenem-resistant enterobacteriaceae: an update on therapeutic options can ceftazidime-avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in enterobacteriaceae? clinical outcomes after combination treatment with ceftazidime/avibactam and aztreonam for ndm klebsiella pneumoniae infection cefiderocol: a novel agent for the management of multidrug-resistant gram-negative organisms patients hospitalized during the new york city pandemic surge key: cord- -pom nktx authors: hong tsui, kan wai title: does a low-cost carrier lead the domestic tourism demand and growth of new zealand? date: - - journal: tour manag doi: . /j.tourman. . . sha: doc_id: cord_uid: pom nktx this study aims to provide a better understanding of the impact of new zealand's low-cost carrier (lcc) on domestic tourism demand and growth. the panel data regression model and the two-stage least-square ( sls) model (aims to control for the endogeneity effects) are used to empirically investigate the impact of lcc and the key determinants affecting new zealand's domestic tourism using five regions (auckland, canterbury/christchurch, dunedin, queenstown, and wellington) from june to july . the findings suggested that the lcc's services, gdp per capita, the regional tourism indicators (accommodation, and food and beverage), and land transport costs affected new zealand's domestic tourism. the policy implications of the key finding regarding the significance of the lcc's operations on new zealand's domestic tourism (local/regional tourism authorities and tourism operators), airline competition between incumbent airline (air new zealand) and the lcc (jetstar), and airport authorities are discussed. the successful low-cost airline business model developed by southwest airlines in the early s has since spread to different parts of the world (chiou & chen, ; francis, humphreys, ison, & aicken, ) . recent literature has suggested that low-cost carriers (lccs) have become one of the key drivers of tourism development for a country or city (e.g. chung & whang, ; dobruszkes & mondou, ; eugenio-martin & inchausti-sintes, ; graham & dennis, ; rey, myro, & galera, ; zhang & lu, ) . the emergence of lccs has attracted different types of air travellers (leisure and business travellers) to visit other destinations with lower airfares, more frequent flights, loyalty programmes, and short turnaround times (e.g. budd, francis, humphreys, & ison, ; chang & hung, ; dresner, ; mason, ) . there seems little doubt that the rapid development of lccs worldwide has had a significant impact on the tourism sector in terms of the transportation of air travellers and the promotion of tourist destinations, as well as the generation of tourists to emerging and mature destinations (clav e, saladi e, cort es-jim enez, young, & young, ) . new zealand is an island country but is one of the popular international tourist destinations for visits, adventure, and sightseeing, thanks to this country's varied natural resources and heritage (e.g. maori culture) (e.g. cloke & perkins, ; pearce, ; ryan, ) . it is evident that most tourism research of new zealand has focussed on international tourism, as inbound and outbound international travel is strong. for and , the total international visitor arrivals to new zealand increased from approximately . to . million (statistics new zealand, a) . in addition, the total number of new zealand residents travelling overseas grew to approximately . million from . million during the same period (statistics new zealand, b) . in contrast, domestic tourism in new zealand has generally been less researched, considering its lesser importance in generating foreign exchange and earnings from the increasing number of international visitor arrivals (pearce, (pearce, , . arguably, international tourists to new zealand cannot always sustain the new zealand tourism industry, especially in the years of economic turmoil (e.g. the global financial crisis of / ) and other exogenous shocks (e.g. the us / terrorist attacks in and the severe acute respiratory syndrome (sars) outbreak in ) (becken & gnoth, ; yeoman et al., ) . although these events have had negative impacts on international tourism in the short term, new zealand's tourism industry still looks promising in the long term, especially when domestic tourism is taken into consideration. in this light, a vibrant domestic tourism can bolster new zealand's tourism industry from the fluctuations of international visitor arrivals, and also generates stability and predictability for its tourism sector (okello, kenana, & kieti, ) . in , the first lcc entered in new zealand's aviation market and had a minimal market share (francis et al., ) . however, jetstar (the subsidiary of qantas) was the first lcc to start scheduled domestic flight services in new zealand since june . to the best of our knowledge, only a few studies have investigated the lcc's impact on new zealand's domestic tourism demand, although this rapidly growing low-cost air transport market deserves a thorough examination. importantly, new zealand's domestic tourism industry exhibited strong growth recently, and there were more than . million domestic guest nights across new zealand's regions and cities in (statistics new zealand, c) . this active and strong domestic tourism demand in new zealand again prompted this study to empirically explore the impact of the lcc (i.e. jetstar) on domestic tourism demand and growth in new zealand. our contribution to the literature and strategic planning and decision-marking for policy makers (e.g. regional/local tourism authorities and tourism operators, airline management, and airports) has emerged from a thorough investigation of the relationship between domestic tourism development and the lcc's operations in new zealand. again, it is generally accepted that the lcc is playing an increasingly important role in new zealand's domestic tourism sector, and there are only a few empirical studies and reports in the area of new zealand's domestic tourism sector. therefore, this study developed the econometric models to investigate the lcc's role in new zealand's domestic tourism development, given that the five key new zealand regions and tourist destinations (i.e. auckland, canterbury/christchurch, dunedin, queenstown, and wellington) are currently served by the lcc (jetstar); these regions took a combined share of . % and . % of the total domestic guest nights in , respectively (statistics new zealand, c . simply, a clear knowledge of the role of the lcc on the tourism demand of new zealand's major regions and tourist destinations can offer a better estimation of domestic tourist flows with further expansion of the lcc's operations to other smaller regions and/or cities. thus the lcc's operations will benefit the future growth of new zealand's domestic tourism demand and local/regional economies. the format of this paper is structured as follows. section provides literature review of the relationship between domestic tourism and lccs, and the determinants that affect domestic tourism. section provides an overview of the lcc serving new zealand's five key regions and tourist destinations (i.e. auckland, canterbury/christchurch, dunedin, queenstown, and wellington) and presents the dataset for analysis. section describes the methodology used to investigate the role of the lcc on new zealand's domestic tourism demand and growth. section presents the empirical findings of the study. section provides a discussion of the key findings and policy implications of this study. the final section summarises the key findings and indicates a direction for future research. two important aspects of domestic tourism and lccs are examined in the following review sections, commencing with the relationship between domestic tourism and the impact of lccs, followed by the determinants affecting domestic tourism. airlines (including lccs) play an important role in linking domestic destinations (prideaux & whyte, ) . air traffic is a strong predictor of tourist arrivals (albalate & fageda, ) . tourism and air transport are explicitly linked, especially in the context of leisure traffic, and demand for air transport services is essentially derived from tourism activities (lei & papatheodorou, ; papatheodorou & lei, ) . most of the demand for lcc operations has been generated by the leisure market, including travellers on vacation and those visiting friends and relatives (vfr) (lawton & solomko, ; mason & alamdari, ) . in tourism and air transport literature, researchers have generally achieved a consensus about the positive impact of lccs on domestic tourism demand and domestic air travel demand. dresner, lin, and windle ( ) suggested that the impact of lccs on communities in the united states associated with the provision of low-cost services, fare reductions, and flight services between specific city-pairs other than neighbouring city pairs. dresner ( ) further mentioned that the growth of lccs has been important to the domestic us market, as lccs transported a higher percentage of leisure passengers. similar situations have been found in australia. whyte and prideaux ( ) suggested that the growth in australian domestic air travel can be attributed to the two lccs (jetstar and virgin blue), and both airlines have benefited the regional tourism of queensland destinations such as cairns. koo, wu, and dwyer ( ) also suggested that lccs in australia have improved air travel access to regions outside the state capital cities in australia by offering discounted tickets and non-stop services from the key domestic origin markets. in addition, recent research by williams and bal a z ( ) pointed out that the low-cost flight activities have had substantial impacts on labour migrants, knowledge, business connectivity/investment, and mobile markets, specifically tourism. in the case of italy, donzelli ( ) also revealed that lccs contribute to job creation and increase tourism revenue, as well as having a significant impact on the local economy of southern italy. moreover, pulina and cort es-jim enez ( ) illustrated how lccs influence the domestic and international tourism demand of the town of alghero (italy). this section reviews the possible determinants that affect domestic tourism. there are relatively few prior studies on domestic tourism demand, and therefore, the literature on both international statistics new zealand records monthly domestic guest nights that domestic tourists spent accommodation at hotels, motels, backpackers, and holiday parks (statistics new zealand, d). and domestic tourism is used to form a framework for this study to examine new zealand's domestic tourism demand and growth empirically. in the tourism literature, habit persistence or repeat visits to key tourist destinations is important for explaining tourism demand (balli, balli, & louis, ; garín-muñoz & montero-martín, ; habibi, ; pearce, ) . air accessibility (koo et al., ; tan, koo, duval, & forsyth, ; whyte & prideaux, ) and the availability of lower airfare services (e.g. low-cost airlines have had a strong impact on domestic air travel) (dresner, ; dresner et al., ) has promoted the growth of domestic tourism in different countries. seasonality and calendar patterns of tourism demand are generally believed to constitute important issues for tourist destinations and tourism operators (chung, ; lim & mcaleer, ) . it is also notable that economic demand-driven variables, such as tourism price variables, affected the number of international and domestic tourists travelling to a destination. these tourism price variables include destination prices or living costs such as accommodation (e.g. cracolici & nijkamp, ; eugenio-martin, ; narayan, ; witt & martin, ) , food and beverage prices (narayan, ; wen, ) , and transportation costs (e.g. divisekera, ; kozak, ; lim, ; prideaux, ) . it has also been suggested that accommodation and food and beverage are the two major sources of tourism revenue (wang, hung, & shang, ) . relating to transportation costs, in the context of tourism demand and air transport demand, distance has been widely applied to estimate domestic and international tourism demand for a destination and/or a city-pair's air traffic volumes based on the gravity model: distances discourage travel between destinations (e.g. hazledine, ; khadaroo & seetanah, ; massidda & etzo, ; morley, rossell o, & santana-gallego, ). in addition, prideaux ( ) claimed transport access cost represents a significant factor in total holiday costs. transportation costs can be grouped into air transport cost and land transport cost (efthymiou & papatheodorou, ; syriopoulos & thea sinclair, ; witt & martin, ) . in particular, witt and martin ( ) suggested that two points relating to transport cost to a destination need to be aware: (i) the substitutability of air transport for surface transport or land transport; and (ii) the increased and decreased attractiveness of near destinations, which are easily accessible by surface transport as compared with more distant destinations for which airfares increase or decrease relative to surface travel costs. income variables (e.g. gross domestic product (gdp) per capita or real income) can also explain domestic tourism demand (athanasopoulos & hyndman, ; garín-muñoz, ; seddighi & shearing, ) . in particular, athanasopoulos and hyndman ( ) found a negative impact of real gdp per capital on domestic tourism (i.e. the number of nights spent for holiday purposes) in australia, and they also argued that australians preferred to travel to foreign destinations than domestic destinations when australia's economy activities improve. in this context, domestic and international destinations behave as substitute goods (massidda & etzo, ) . furthermore, the exchange rate (another important economic factor used to analyse international tourism demand) between the origin country and a foreign country has been consistently used in modelling international tourism demand (song & li, ; because it has significant effect upon inbound and outbound tourism demand and can be treated as the pull and push factors of tourism demand (e.g. hanqin & lam, ; prideaux, ; schiff & becken, ; webber, ) . in addition, martin and witt ( ) noted that the cost of travel to a substitute destination could be expected to be a factor in destination selection. exogenous shocks and crisis events (e.g. the us / terrorist attacks in , the sars outbreaks in , the global financial crisis in / , the christchurch earthquakes in ) are believed to have negative effects upon tourism demand (tsui, gilbey, & balli, ; voltes-dorta, jim enez, & su arez-alem an, ; wang, ; yeoman et al., ) . regarding the impact of terrorism, voltes-dorta et al. ( ) suggested that the ceasefire from the terrorist organisation in spain has a significant positive impact on the number of visitors. in new zealand, tsui, gilbey and balli ( ) found that the christchurch earthquakes in had a significant adverse effect on passenger numbers via the christchurch international airport. similarly, mazzocchi and montini ( ) found that local tourist arrivals in assisi (central italy) fell dramatically after the earthquake. the panel dataset of new zealand's five key regions and tourist destinations (i.e. auckland, canterbury/christchurch, dunedin, queenstown, and wellington) from june to july was assembled using a variety of sources (see table ). data for the number of domestic guest nights and the total guest nights of the five regions in new zealand were collected from statistics new zealand. in order to measure the impact of the lcc (jetstar) on new zealand's domestic tourism demand and growth, i also collected information on available seat kilometres (asks) scheduled by the lcc (jetstar) and all the commercial airlines (air new zealand) to the airport located in each region from the official airline guide (oag). it should be noted that there is only one commercial airport per city across new zealand. data on the gdp per capita in new zealand were also collected from statistics new zealand for capturing the level of income of the new zealand population for domestic holidays and travel propensity. in addition, i measured the effect of the exchange rate with regards to the substitution effect of international and domestic vacations; the exchange rate between the new zealand and us dollars was retrieved from the reserve bank of new zealand. furthermore, two main regional tourism indicators (rtis) (the tourism price indices: accommodation, food and beverage) were obtained from the ministry of business innovation & development. transport costs (aviation fuel price and petrol price) for domestic visitors to travel to a destination were collected from the ministry of transport. the two rtis and transport costs aim to grasp the effect of the price levels that domestic tourists and holidaymakers paid for visiting and travelling to the sampled regions and/or cities in this study. as shown in table , i have also created two dummy variables (the global financial crisis / and the christchurch earthquakes ) to capture the perceived negative impacts of these exogenous crises on domestic tourism demand in new zealand. these two dummy variables take the value of when the crises occurred and otherwise. the monthly dummy variables (seasonal the concept behind the push and pull dimension is that people travel because they are pushed by their own internal forces and pulled by the external forces of destination attributes (hanqin & lam, ) . dummies) were also created to capture the fluctuation in seasonal patterns of new zealand's domestic tourism demand. auckland, canterbury/christchurch, queenstown, and wellington regions are always the four most popular domestic tourist destinations in new zealand. fig. shows monthly domestic guest nights and monthly asks scheduled by the lcc for the studied regions and their respective shares for each of the regions for the period of june ejuly . in fig. , the time series of the monthly domestic guest nights and the monthly lcc's asks for the five new zealand regions exhibited different patterns, alongside the possibility of seasonal patterns. note that new zealand's domestic tourism has the characteristics of shorter stays and a strong visiting friends and family sector (ministry of business, innovation & employment, ). the auckland region leads the group with an average of , domestic guest nights per month, followed by canterbury/christchurch ( , ), wellington ( , ), queenstown ( , ), and dunedin ( , ). accordingly, the lcc's monthly average ask for auckland airport is approximately . million, followed by christchurch airport ( . million), wellington airport ( . million), queenstown airport ( . million), and dunedin airport ( . million). in addition, the shares of domestic guest nights of the total guest nights (domestic and international) for all five regions exceed %, except for queenstown has a share of . %. the lower share of domestic guest nights for the queenstown region indicates that it handled more international tourists than domestic tourists during the study period. however, the shares of the lcc's services for all the studied airports are between . % and . %: queenstown airport ( . %), auckland airport ( . %), christchurch airport ( . %), wellington airport ( . %), and dunedin airport ( . %). these figures suggest that the lcc plays a significant role in new zealand's domestic aviation market in transporting air travellers between the key cities and tourist destinations (official airline guides, ; statistics new zealand, c). detailed explanations of all the variables of interest are shown in table . the descriptive statistics for all variables of interest (in logarithmic form) for the period of june ejuly are shown in table . two dependent variables, ln(domestic guest nights) it and (%) of domestic guest nights it are the number of domestic guest nights and the share of domestic guest nights of the total guest nights (domestic and international) of a region, respectively. the variables ln(domestic guest nights) it- , ln(lcc's ask) it , (%) of lcc's ask it , ln(gdp per capita) t , ln(rti-accommodation, food & beverage) it , ln(aviation fuel price) t , ln(petrol price) t , and exchange rate (nzd vs. usd) t are used as the explanatory variables in the panel data regression models, together with three dummy variables (global financial crisis / , christchurch earthquakes , and seasonal dummies) to capture their impacts on new zealand's domestic tourism. the descriptive statistics in table shows that the distribution of eight time series variables, ln(domestic guest nights) it , (%) of domestic guest nights it , ln(lcc's ask) it , (%) of lcc's ask it , ln(rti-accommodation) it , ln(aviation fuel price) t , ln(petrol price) t , and exchange rate (nzd vs. usd) t are skewed to the left. the remaining variables in this study are skewed to the right and peaked with respect to their respective skewness and kurtosis values. in addition, the multicollinearity among all the variables of interest was verified by the correlation matrix of variables; the test results show no significant correlations among the explanatory variables in the dataset. to estimate the panel data regression models, all the variables of interest need to be stationary in order to avoid the problem of spurious correlation (alba & papell, ; balli et al., ) . therefore, the panel unit root tests were performed to test the stationarity of all the variables of interest investigated in this study. the results of panel unit root tests show that all the variables of interest are stationary, except the variables ln(gdp per capita) t , ln(rti-accommodation) it , ln(rti-food & beverage) it , ln(aviation fuel price) t , ln(aviation fuel price) t , and exchange rate (nzd vs. usd) t . therefore, first-order differencing was applied to these six nonstationary variables to make them become stationary. prior literature shows that lccs can have a significant impact on the tourism demand and tourism growth of a county or city. as the case for other destinations, new zealand's domestic tourism demand and growth may be affected by the factors and variables discussed in section . therefore, this study developed econometric models to investigate new zealand's domestic tourism demand and growth. following the demand function of chi, koo, and lim ( ) , this study specified new zealand's domestic tourism demand and growth as a function of the lcc's seat capacity (asks), gdp per capita, two rtis (accommodation, food and beverage), transport costs (aviation fuel price and petrol price), the exchange rate, other exogenous variables (the global financial crisis of / and the christchurch earthquakes of ), and seasonal dummies. importantly, the rapid development and expansion of the lcc's operations (jetstar) within new zealand's domestic aviation market and its impact on domestic tourism have been less studied than international tourism. this study aimed to fill this gap and used the lcc's seat capacity/per region panel dataset to investigate its impact on new zealand's domestic tourism demand and growth, as well as identifying the variables that influenced tourism demand for the five key new zealand regions and tourist destinations (i.e. auckland, canterbury/christchurch, dunedin, queenstown, and wellington) for the period of june ejuly . two panel data regression models were used to investigate the impact of lcc's services on new zealand's domestic tourism demand and growth as specified as below: model : model : where i and t denote region i and month t, respectively; ln denotes the logarithm; b s indicates the coefficients to be estimated; ε it is the disturbance term. the statistical program of eviews was used for the estimation. it should be noted that the variable ln(domestic guest nights) it in model represents the number of domestic guest nights (a proxy for the number of domestic tourists and holidaymakers) of region i at month t, and the variable (%) of domestic guest nights it in model represents the share of domestic guest nights of the total guest nights of region i at month t. in addition, the variable (%) of lcc's ask it in model indicates the share of the lcc's seat capacity (jetstar) provided at an airport; this variable is a measure of dominance which is a percentage of the total lcc's ask in a particular region (vowles, ) , and also it indicates the lcc's position against the incumbent airline (air new zealand) in transporting domestic tourists and holidaymakers between new zealand's regions and cities. table presents the estimation results of the panel data regression models and the two-stage least-square ( sls) models: model ( ) -ln(domestic guest nights) it and model ( ) -(%) of domestic guest nights it . during the panel data regression analysis, the problem of endogeneity in model a may provide inconsistent estimators or biased estimation results. note that the endogeneity effect violates the assumptions of ordinary least squares (ols), and thus the ols estimator is biased, inconsistent and no longer the best linear unbiased estimator (blue) (chi et al., ) . in this study, the variable ln(lcc's ask) it in model a can be endogenous, as an increase in airline seat capacity for an airport increases the number of tourists and holidaymakers using airline services to travel to the region where the airport is located, which, in turn, influences the total seat capacity scheduled by airlines. thus this study used the instrumental variable (iv) technique to correct the problem of endogeneity (e.g. borenstein, ; hsiao, ; tsui, tan, & shi, ; wooldridge, ) . the iv technique used to correct the problem of endogeneity is shown below: as mentioned above, the variable ln(lcc's ask) it is likely to be an endogenous variable in model a. herfindahlehirschman index (hhi index), which is an instrumental variable to measure airline market competition (it is calculated on the basis of the total asks an airline scheduled for an airport as a share of the whole) in new zealand's domestic aviation market: the lcc (jetstar) vs the incumbent airline (air new zealand). the predicted variable ln(lcc's ask) it was also obtained. as expected, the hhi index is to have a negative coefficient during the first-stage regression analysis. as a region becomes more competitive, competition increases and lcc's ask decreases (fageda, jim enez, & perdiguero, ) . the endogenous variable ln(lcc's ask) it is replaced with its predicted value during the second-stage regression analysis. because the predicted values are uncorrelated with the error terms in the regression models, this iv technique can produce an unbiased coefficient from which the causality between ln(domestic guest nights) it and ln(lcc's ask) it can be inferred. it should be noted that model a contains the endogenous variable ln(lcc's ask) it , and the ols estimators in the model are biased and inconsistent. therefore, the subsequent interpretation and further analyses of the empirical results in this study were based on the sls models ( b and c). the estimates obtained from these two sls models are quite consistent and perform satisfactorily, as the magnitude and the signs of the coefficients seem to be theoretically reasonable and significant. in addition, the estimators can be interpreted, as elasticities as the model specification of model is in double-logarithmic form. in examining the effect of total seat capacity scheduled by the lcc on new zealand's domestic tourism demand and growth, the variable ln(lcc's ask) it is reported to be a highly significant factor in all models affecting the variable ln(domestic guest nights) it in all the regions. for example, models b and c suggest that a % increase in the total seat capacity scheduled by the lcc (jetstar) to the sampled regions is associated with a . e . % increase in the number of domestic guest nights (meaning more domestic tourists visited and stayed at the studied regions). the elasticities of the variables ln(lcc's ask) it and ln(domestic guest nights) it reported in both models ( b and c) are in line with the study of vowles ( ) , claiming that a lcc provides low-cost service will have a strong effect in airfare price of a destination. similarly, the study of ryan and birks ( ) claimed that airfare of a lcc is significant below that charged by full-service carriers in trans-transman route, and their finding supported australasian experience and the european experience. considering the effect of repeat visits to the sampled regions in this study, the variable ln(domestic guest nights) it- (the one-period lag of the dependent variable) is added to model c as another explanatory variable. this variable aims to capture the dynamic information of the tourist numbers dataset, and the result shows that repeat visits or habit persistence is important in explaining the number of domestic guest nights of new zealand's domestic tourism. the income level variable ln(gdp per capita) t was also found to boost new zealand's domestic tourism demand and growth, with a statistically significant parameter in model b. this result is consistent with our expectation and indicates that a % increase in the income per capita of the new zealand population stimulates a . % increase in domestic guest nights of the sampled regions; this also implies that the growth in the income level of the new zealand population will increase domestic tourism demand. in contrast to other studies of domestic tourism demand, the estimation results show that two regional tourism indicator variables ln(rti-accommodation) it and ln(rti-food & beverage) it for domestic tourists and holidaymakers to stay and visit the sample regions are reported to have positive significant estimators in models b and c. these elasticities suggest that a % increase in accommodation prices and food and beverage prices still produce a . e . % and . e . % increase in the number of domestic guest nights for the sampled regions, respectively. this may be because new zealand's domestic tourists and holidaymakers are not particularly concerned with increasing tourism-related costs and expenditure during their domestic trips even after the improvement in income per capital and higher spending power. it should be noted that new zealand's gdp per capita grew from approximately nz$ , in to nz$ , in , equalling a . % increase (new zealand government treasury, ) . furthermore, two transport costs paid by domestic tourists to travel to a destination: air transport cost variable ln(aviation fuel price) t could not be found to be a significant variable affecting new zealand's domestic tourism demand in all the models. land transport cost variable ln(petrol price) t was found to have a significant impact on new zealand's domestic tourism demand in model b only but not in other models. this interesting empirical finding of ln(petrol price) t is logical and expected by considering driving is the most common form of transport among new zealand residents and domestic tourists to travel to their holiday destinations. in addition, the estimation results for all models show that the variable exchange rate (nzd vs. usd) t is not an important factor for explaining new zealand's domestic tourism demand and growth. it should be noted that this variable is used as the proxy for the "substitute goods" of international vacations over domestic vacations by considering the strength of the new zealand currency against the us dollar (one of the most commonly used currencies worldwide). this result is consistent with our expectation that the fluctuation (stronger or weaker) in new zealand currency would not affect domestic tourism demand and growth, as the number of domestic tourist guest nights for the five sampled regions maintained their growth trends at different magnitudes from the exchange rate's trend (see fig. ). the dummy variables global financial crisis / and christchurch earthquakes have been included to capture their negative impacts on new zealand's domestic tourism. their expected significant negative impacts on domestic guest nights are not reported in the models. in addition, the seasonal dummies variables are included for controlling the fluctuation in domestic tourism patterns and demand in new zealand but found mixed results across the models due to different explanatory variables included in the models. importantly, looking at the position of lcc (jetstar) in new zealand's domestic aviation market to serve and support domestic tourism in model a, the variable % of ln(lcc's ask) it is reported to be statistically significant and positive. this positive significant estimator further support the findings of the two sls models ( b and c), in which the variable ln(lcc's ask) it has a significant impact on the variable ln(domestic guest nights) it or the lcc positively affected new zealand's domestic tourism demand and growth. as a robustness check, this study also applied the differencein-difference (did) approach to identify and verify the lcc's impact (the treatment) on new zealand's domestic tourism demand and growth (i.e. domestic guest nights). the basic intuition of the did approach is that to study the impact of the 'treatment', one compares the performance of the treatment group during the pre-and post-lcc periods relative to the performance of control group during the per-and post-lcc periods (albalate & fageda, ; slaughter, ; wooldridge, ) . however, for this assumption to be valid it is necessary to demonstrate that both treatment and control groups are similar (or is the same) in the absence of treatment (the entry of lcc). note that jetstar started its low-cost services (the treatment) in new zealand since june . to perform the did analysis, ten new zealand regions/airports were selected and divided into two groups: ( ) treatment regions/airports have lcc's services (auckland, canterbury/ christchurch, dunedin, queenstown, and wellington); and ( ) control regions/airports have no lcc's services (hamilton, palmerston north, rotorua, taupo, and whangarei). the analysis period of the did estimation covers january to july . that is, the difference between domestic guest nights for treatment regions and control regions during the pre-and postperiods of lcc's services. the did model was used to investigate the impact of lcc on new zealand's domestic tourism demand and growth as specified table difference-in-difference (did) estimation and panel data regression model of the impact of low-cost carrier on new zealand's domestic tourism (january ejuly ). did estimation panel data regression model remarks: ** and *** indicate that the explanatory variable is significant at the . and . significance level, respectively. t-statistics are printed in parentheses. the difference-in-difference estimation is based on the ols estimation. the results of hausman test verified that the panel data regression model favoured using the random-effect model. considering new zealand's small geographic areas and its unique airport operating environment (only one commercial airport per city across new zealand), it is difficult to find the similarity between the treatment regions and the control regions prior to the entry of lcc for assessing the plausibility of the fundamental identifying assumption. the main reasons are that the five key regions (auckland, canterbury/christchurch, dunedin, queenstown, and wellington) with lcc's services have higher income levels, larger population size, and more tourism flows compared with other smaller regions. as below: model : where i and t denote region i and month t, respectively; b s indicates the coefficients to be estimated; the variable trend denotes the time trend that is common to the treatment and control regions or it tries to control the general changes (a trend) across the treatment and control regions over time; the dummy variable d(treat_region) it denotes the treatment regions have lcc's services (treatment regions with lcc's services equals to and control regions without lcc's services equals to ); d(post_lcc) it is the dummy variable for the post-lcc period (the post-lcc period equals to and otherwise); the b is the parameter of interest (i.e. the did estimator), which is the interaction term d(treat_region) it * d(post_lcc) it , providing the difference in domestic guest nights between the treatment and control regions before and after receiving lcc's services; ε it is the disturbance term. the did estimator is reported to be a statistically significant and positive coefficient in table , which suggest that there is a positive impact of lcc's services on the number of domestic guest nights in new zealand. importantly, the significant did estimator obtained from the did approach is consistent with the empirical findings of panel data regression analysis reported in table (models b and c). to take advantage of the larger dataset established for the did analysis above, this study also applied the similar model specification used in model in section (model specifications and econometric method) and incorporated the variable lcc dummy it into model below. note that this variable lcc dummy it replaces the variable ln(lcc's ask) it in model in section , and it is a binary variable to capture the impact of lcc's services upon new zealand's domestic tourism demand and growth (auckland, canterbury/ christchurch, dunedin, hamilton, palmerston north, queenstown, rotorua, taupo, wellington, and whangarei) for the period of january ejuly . model : where i and t denote region i and month t, respectively; b s indicates the coefficients to be estimated; the variable lcc dummy it is a binary variable that takes after the entrance of lcc's services for the airport of region i at time t and otherwise. in table , most significant coefficients reported in the panel data regression model are largely consistent with those of the did estimation, particularly the key variable lcc dummy it was reported to be a statistically significant and positive coefficient in the panel data regression model. coupled with the empirical findings of the did analysis, the results of the panel data regression model in table also provide strong evidence regarding the lcc (jetstar) has a significant impact on zealand's domestic tourism demand and growth. this study reported that the low-cost air transport services provided by the lcc (jetstar) in new zealand's domestic aviation market had a significant effect on domestic tourism demand and growth. importantly, the evidence of the lcc's significance for domestic tourism demand and growth in this study is consistent with the findings of other recent literature that investigated the relationship between lccs' expansion and tourism and economic growth in different countries (e.g. donzelli, ; koo et al., ; pulina & cort es-jim enez, ; whyte & prideaux, ; williams & bal a z, ) . considering the key findings of this study, special consideration must be given to the recent rapid development of jetstar and its future potential role in new zealand's domestic tourism and aviation sectors with new connectivity to more regional destinations. it is recognised that jetstar adopted aggressive marketing strategies to launch its scheduled budget air travel services for air travellers to fly to four more domestic cities in new zealand, namely napier, nelson, new plymouth, and palmerston north, starting from late and early (australian aviation, ) . this rapid expansion of lcc's services in new zealand's domestic aviation market is likely to stimulate and boost air travel demand with discounted tickets; this will continuously develop and benefit new zealand's regional economies as well as the tourism and aviation sectors, particularly considering the significant domestic tourism expenditure and the significant number of staff employed in the tourismand aviation-related sectors. for the amount of domestic tourism expenditure generated, there was approximately nz$ , million and nz$ , million in domestic tourism expenditure recorded in and , respectively, equalling the growth of . % over the years (statistics new zealand, e) . this situation is echoed by the increasing growth trends for the total guest nights (domestic and international guest nights) and the number of guest arrivals for all of the five key regions and tourist destinations in new zealand that are connected by jetstar's networks between and (see fig. ). in comparison with international tourism expenditure, domestic tourism expenditure plays an even more significant role in contributing towards new zealand's lnðdomestic guest nightsÞ it ¼ b þ b trend þ b dðtreat regionÞ it þ b dðpost lccÞ it þ b d À treat regionÞ it *dðpost lccÞ it þ b lnðgdp per capitaÞ t þ b lnðrti À accommodationÞ it þ b lnðrti À food & beverageÞ it þ b lnðaviation fuel priceÞ t þ b lnðpetrol priceÞ t þ b exchange rateðnzd vs: usdÞ t þ b global financial crisis = þ b christchurch earthquakes þ b lnðhhi indexÞ it þ ε it lnðdomestic guest nightsÞ it ¼ b þ b ðlcc dummyÞ it þ b lnðgdp per capitaÞ t þ b lnðrti À accommodationÞ it þ b lnðrti À food & beverageÞ it þ b lnðaviation fuel priceÞ t þ b lnðpetrol priceÞ t þ b exchange rateðnzd vs: usdÞ t þ b global financial crisis = þ b christchurch earthquakes þ b lnðhhi indexÞ it þ b seasonal dummies t þ ε it economy during the same period: domestic and international tourism expenditure contributed a total of , million ( . %) and , million ( . %) to new zealand's total tourism expenditure in , respectively (see fig. ). as indicated in section (introduction), the empirical findings of this study have important implications for strategic planning and policy-setting by the local/regional tourism authorities and tourism operators, airline management, and airports regarding the best strategies and/or best approaches for attracting and transporting more tourists for visitation purposes. first, this study shows the existence of a strong relationship between the lcc's services (or the proliferation of air travel) and new zealand's domestic tourism demand and growth, and this will help provide a more accurate and robust assessment of the impact of the lcc's operations and the necessary resources for advertising and promotion campaigns by the local/regional tourism authorities and tourism operators to promote their regions as attractive tourist destinations for domestic and international tourists. second, in light of the substantial growth in domestic and international tourists and holidaymakers travelling within new zealand, fierce competition between the incumbent carrier (air new zealand) and the lcc (jetstar) will become apparent to capture the market share using different approaches (e.g. fare levels, destinations served, and frequency improvement, etc). it is expected that airline competition between air new zealand and jetstar is likely to benefit and boost new zealand's domestic tourism demand. given the nature of domestic tourism in new zealand and its unique geographical landscape with two separate islands, it is also likely that the future growth of jetstar's operations and networks will further affect air new zealand's operations in terms of its schedule planning and fare levels for the trunk and regional routes. it is evident that air new zealand is now planning a significant shakeup to its domestic networks involving additional capacity being added onto the main trunk routes (e.g. auckland, christchurch, and wellington) and some regional routes against its domestic rival jetstar (australian aviation, ). similarly, the rapid growth of lcc's operations in new zealand's domestic aviation market will also impact other travel modes (e.g. land transport) to transport travellers and tourists across regions and cities. research into the impact of lcc's services on other choices of transport (or intermodal competition) is not within the scope of this study. third, for the airports in other smaller regions in new zealand, significant investment in the redesign and upgrade of terminal spaces and the purchase of other equipment is required to facilitate the entry of the lcc (jetstar), as its ability to transport more tourist arrivals (particularly budget travellers) who pass through the airports is vital. lccs worldwide have achieved substantial growth in recent years, bringing significant impacts and benefits to local/regional tourism and economies. the panel data regression model and the panel data sls model (which aims to control for the endogeneity effects) were used to empirically investigate the impact of lcc's services and the key determinants affecting new zealand's domestic tourism demand and growth using five key new zealand regions and tourist destinations (auckland, canterbury/christchurch, dunedin, queenstown, and wellington) for the period of june ejuly . first, the empirical results of this study revealed that the lcc (jetstar) has significantly increased and boosted new zealand's domestic tourism demand. the empirical findings of this study regarding the significant impact of lcc's services on new zealand's domestic tourism are largely consistently with prior literature, regarding regional tourism growth and economy development resulting from the improvement of air access and the provision of discounted tickets for budget travellers. in addition, gdp per capita, the rtis (accommodation, and food and beverage), land transport costs are also found to have affected new zealand's domestic tourism during the study period. the message underlying the key findings of this study is that the local/regional tourism authorities and tourism operators in new zealand should further recognise the significant role of air transport (especially the lcc (jetstar) offers low-cost domestic air travel with discounted tickets as well as the likely impact of intermodal competition between air transport and land transport on tourism demand and growth). this study also allows better assessment of the growth of tourist arrivals (domestic and international) and tourism activity for a region or city with the entry of the lcc, particularly considering the recent rapid expansion of lcc's operations in new zealand's domestic aviation market. for the growth of low-cost air travel and the associated benefits for the local/ regional tourism industry and economy, it is important for the local/regional governments and airport authorities to plan and provide sufficient airport capacity and better equipment to accommodate existing and future lcc's operations, and to handle the increasing amount of tourist numbers and budget travellers. two potential limitations of this study are observed: (i) data of domestic guest nights in this study did not indicate the length of stay (e.g. less than one day) and types of accommodation (e.g. hotels, motels, backpackers, and holiday parks) where domestic tourists have stayed, which may have limited the robustness of the empirical findings of lcc's impact on new zealand's domestic tourism. this is because the length of stay and types of accommodation stayed at a destination can be affected by travel purposes (e.g. vfr, work and business, holiday, and backpacking). however, the current approaches in this study to estimate the lcc's impact on domestic guest nights in new zealand are largely decided by the availability of tourism data from statistics new zealand. as the extension of this study, an in-depth study is recommended to forecast the number of visitor arrivals in different classes (e.g. vfr, business visitors, holiday visitors, and backpacker visitors) for all the regions in new zealand that have and will be served by the lcc. this would further allow insight to the impact of lcc's services (especially the impact of budget fares on different classes of tourists) on new zealand's regional tourism sector and economic growth; and (ii) this study did not investigate the effect of tourism demand spillover upon tourist flows between the regions (i.e. the geographical effect). yang and wong ( ) claimed that the term of spillover effect refers to the indirect and unintentional effects that a region's sector exerts on tourism flows to other regions. for example, if queenstown (the popular tourist destination in new zealand) cannot accommodate the increase in domestic and international tourist arrivals during the peak travel seasons with sufficient star-rated hotel rooms. as the result, many tourists may choose to stay at christchurch and drive to queenstown as the driving time is approximately hours. therefore, a further analysis is recommended to investigate the spillover of tourist flows across new zealand using the similar approach of yang and wong ( ) . this would allow insights to domestic and international tourist spillovers for the popular tourist destinations in new zealand. notably, tourism demand spillover (or passenger demand spillover of new zealand's domestic tourism) will also impact airline operations and revenues while considering the difference between observed demand (bookings) and true demand for a particular flight and/or destination. for example, if air new zealand's scheduled seat capacity cannot meet the true demand of international and domestic tourists to a destination (e.g. queenstown) during the peak travel seasons because of capacity constraints or booking control limits imposed on various fare classes. three common situations can then be observed: revenue losses, the displacement between international and domestic tourists, or the spilling of demand through refusing further reservations from tourists or passenger demand turned away. in particular, spilled tourists may be lost to jetstar or may be accommodated on other flights of air new zealand (belobaba & farkas, ) . the challenges facing an airline (irrespective of air new zealand or jetstar in this study) is to use revenue management to better allocate and sell airline seat inventory while improving passenger revenues; prior literature shows that airlines with revenue management will benefit incremental revenue gains of e % (belobaba, international tourism as % of total tourism expenditure doemstic tourism as % of total tourism expenditure international tourism expenditure domestic tourism expenditure this, air new zealand and jetstar need to know the distribution for the expected high-fare true demand and schedule the popular destinations in new zealand with larger airplanes through fleet assignment during the peak travel seasons (swan, ) . 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zealand's major regions: a panel data approach. urban studies, e the impact of eta's dissolution on domestic tourism in spain the effect of low fare air carriers on airfares in the us the impact of crisis events and macroeconomic activity on taiwan's international inbound tourism demand. tourism management air deregulation in china and its impact on airline competition e measuring the cost efficiency of international tourist hotels in taiwan exchange rate volatility and cointegration in tourism demand china's domestic tourism: impetus, development and trends impacts of low cost carriers on regional tourism low-cost carriers, economics of flows and regional externalities econometric models for forecasting international tourism demand econometric analysis of cross section and panel data a spatial econometric approach to model spillover effects in tourism flows tourism : scenario for new zealand low cost carriers in china and its contribution to passenger traffic flow his research covers different areas, and includes airline and airport demand forecasting, airport productivity and efficiency, and tourism activities and future trends and its relationship with air transport industry key: cord- -ko bdvo authors: vasilakis, nikos; tesh, robert b.; popov, vsevolod l.; widen, steve g.; wood, thomas g.; forrester, naomi l.; gonzalez, jean paul; saluzzo, jean francois; alkhovsky, sergey; lam, sai kit; mackenzie, john s.; walker, peter j. title: exploiting the legacy of the arbovirus hunters date: - - journal: viruses doi: . /v sha: doc_id: cord_uid: ko bdvo in recent years, it has become evident that a generational gap has developed in the community of arbovirus research. this apparent gap is due to the dis-investment of training for the next generation of arbovirologists, which threatens to derail the rich history of virus discovery, field epidemiology, and understanding of the richness of diversity that surrounds us. on the other hand, new technologies have resulted in an explosion of virus discovery that is constantly redefining the virosphere and the evolutionary relationships between viruses. this paradox presents new challenges that may have immediate and disastrous consequences for public health when yet to be discovered arboviruses emerge. in this review we endeavor to bridge this gap by providing a historical context for the work being conducted today and provide continuity between the generations. to this end, we will provide a narrative of the thrill of scientific discovery and excitement and the challenges lying ahead. almost years have passed since walter reed, james carroll, aristides agramonte, and jesse lazear established that yellow fever is caused by a filterable infectious agent which is transmitted by the bite of a mosquito, then known as stegomyia fasciata (aedes aegypti). lazear, who like his colleagues, had been stationed by the us army in cuba to study the disease, died of yellow fever in september after being exposed experimentally to mosquitos that had fed on sick patients. at about the same time in south africa, james spreull and sir arnold theiler demonstrated that bluetongue disease of sheep is caused by an "ultravisible" agent that could be transmitted by the injection of an infected serum. epidemiological evidence suggested that the agent was vector-borne, and it was subsequently shown by r.m. du toit that the disease occurred in sheep inoculated experimentally with suspensions of wild-caught biting midges (culicoides imicola). these and other seminal discoveries precipitated a century of research into vector-borne and zoonotic viral diseases, resulting in the discovery and isolation of many hundreds of novel viruses from insects or vertebrate hosts. some were identified as important human or veterinary pathogens. many other viruses were archived in reference collections, with only basic characterization of their biological or molecular properties. in recent years, the advent of next generation sequencing (ngs) has transformed this situation. complete genome sequences are now available for many of the archived isolates, allowing more accurate taxonomic assignments, analysis of their phylogenetic and evolutionary relationships with other viruses, and evaluation of the potential risks they may present to humans and wild or domestic animal populations. ngs has also opened the door to viral metagenomics, which has greatly increased the pace of new virus discovery from a wide range of hosts, usually with complete or near-complete viral coding sequences, but no virus isolate and minimal biological data. this has presented both opportunities and challenges for virologists and epidemiologists, as well as viral taxonomists, evolutionary biologists, and bioinfomaticians. sadly, this technological revolution has been accompanied by a period of progressive disinvestment in training in classical virology. in this review, we recall the rich history of the discovery of arboviruses and other zoonotic viruses in various settings around the world and the many outstanding scientists who have contributed to the endeavour. we also consider the impacts of ngs and metagenomic analysis, and the implications of these new technologies for the future of this important field of research. the rockefeller foundation (rf) was organized in for "the well-being of mankind throughout the world" [ ] . at the time, yellow fever was still epidemic in many tropical and subtropical regions of africa and the americas, so in , the rf established the yellow fever commission, with the lofty goal of eradicating yellow fever from the world. during the next years, the rf supported an international group of scientists working on yellow fever in new york city in the united states (u.s.); rio de janeiro and salvador in brazil; bogota, colombia; yabba, nigeria; and entebbe, uganda [ , ] . much of the work and accomplishments of rf-funded personnel during this period was described in strode's classic book, entitled "yellow fever" [ ] . the major accomplishments included: confirmation of earlier work by the reed commission in cuba, demonstrating that yellow fever was caused by a filterable agent, yellow fever virus (yfv), that was transmitted by the bite of infected mosquitoes, aedes aegypti; . discovery that the rhesus monkey and the white mouse are susceptible to infection with yfv, providing models for subsequent studies on the pathogenesis, transmission, epidemiology, and control of the disease; . demonstration that convalescent sera of humans and animals infected with yfv neutralize the virus. this discovery led to the development of the mouse neutralization test, which allowed investigators to map the geographic distribution of the virus; . discovery of the forest or sylvan cycle of yfv and the importance of mosquitoes other than ae. aegypti in the transmission and maintenance of the virus; . development of the d vaccine strain of yfv and its first human trials. max theiler, son of south african bluetongue researcher sir arnold theiler, received a nobel prize in for this work. as a by-product of the overseas yellow fever investigations, rf-funded researchers also isolated a number of other previously unknown arboviruses, including west nile, zika, semliki forest, bunyamwera, bwamba, uganda s, ilheus, and anopheles a and b viruses [ ] . the threat and onset of world war ii changed the priorities of the rf, and most of its overseas yf research activities ceased during this period. many of the former american rf staff became involved in studies of diseases of military importance, such as typhus, malaria, sandfly fever, and dengue, some as civilians and others as members of the u.s. armed forces. in , after the end of the war, the rf decided to develop a major new program to study arthropod-borne viruses and to discover "what might be out there", as well as their disease associations, life cycles, and vectors. this led to the development of the rockefeller foundation virus program, a world-wide virus discovery program that was funded from to [ ] . over the next several years, field laboratories staffed by both rf and local scientists were established with foreign governments in pune, india; port of spain, trinidad; belem, brazil; johannesburg, south africa; ibadan, nigeria; cali, colombia; and cairo, egypt [ ] . in egypt, the cairo laboratory was associated with the u.s. naval medical research unit no. . scientists in these field laboratories were involved in the detection and investigation of human diseases in their respective geographic regions, surveying human and animal populations for serologic evidence of past viral infection, and searching for viruses in a wide variety of arthropods, mammals, birds, reptiles, and amphibians [ ] . all virus isolations were done on site, using the classic technique of intracranial inoculation of newborn white mice, but later, as vertebrate cell cultures became available, inoculation of cell cultures was also used. in addition, sentinel animals, such as non-human primates, mice, and hamsters, were also used in the field to detect virus activity. viruses isolated in the overseas laboratories were initially characterized locally, lyophilized for preservation and storage, and then aliquots of each new virus were shipped back to the rf central virus laboratory in new york for further characterization and study. it was during this period that jordi casals, delphine clarke, loring whitman, and others developed the sucrose-acetone method for preparation of viral antigens and began to adapt the hemagglutination inhibition (hi) and complement fixation (cf) tests to identify and group arboviruses [ ] [ ] [ ] . the rf virus program was extremely productive and many novel arboviruses, as well as non-arthropod-borne viruses (i.e., hantaviruses and arenaviruses), were discovered by rf-funded investigators during this period. the productivity of this search strategy in detecting novel viruses affecting humans was recently reviewed by rosenberg et al. [ ] . the virus discovery rate was highest in the period - , which coincided with the rf virus program. a similar approach was also practiced by the institut pasteur and other international groups involved in virus discovery during this period, as described in this article and in other publications [ ] [ ] [ ] [ ] [ ] [ ] , resulting in the detection of a high proportion of pathogenic arboviruses. the second advantage of the strategy was that it yielded actual virus isolates, whose pathogenesis could be studied experimentally in vivo and in vitro in vertebrate and arthropod models. in contrast, current search methods for new viruses, which generally use metagenomics and other sophisticated genetic techniques to detect novel viral agents, do not usually yield live viruses, only their nucleotide sequences. a complete or partial genetic sequence alone rarely provides insight into the epidemiology and ecology, host range, pathogenesis and disease potential, or transmission modes of the new viruses. in , the rf made a decision to phase-out its virus program and to devote more of its efforts and resources to other projects, such as population control and increasing food production ("the green revolution"). over the next years, the rf-funded investigators working in overseas laboratories were withdrawn and the respective laboratories were turned over to local institutions or governments. in , the rf made arrangements with yale university to transfer its arbovirus group to new since the establishment of the institut pasteur in paris in , louis pasteur sent collaborators to various countries, mainly in the french colonies of indochina and africa. in that early time, pasteur wanted to set up rabies centers where the disease was highly and dramatically prevalent; naturally, the research potential of these centers was rapidly extended to tropical infectious diseases [ ] . currently, spread among countries on five continents, there are institutions, of which bear the name of "institut pasteur" (ip). altogether, these institutions constitute a structure long called the "institut pasteur d'outre-mer", which in became the international network of pasteur institutes (réseau international de l'institut pasteur, riip) and associated institutes. from this emerging network, the first african laboratory for microbiology was created in saint louis, senegal in , and then transferred to dakar to become the pasteur institute of dakar (institut pasteur de dakar, ipd yellow fever was to play a key role in the research at ipd. in the s, ipd had developed a vaccine against yellow fever (strain fnv) and produced it commercially. the re-emergence of yellow fever in africa in the s occurred mainly in the savannah zone and revealed the lack of knowledge about the natural maintenance of the virus during the inter-epidemic period. a large study to understand the emergence and re-emergence of sylvatic yellow fever was established between the ipd, institute pasteur abidjan (ipa) in côte d'ivoire, and institute pasteur bangui (ipb) in the central african republic, in order to detect the circulation of the yfv and map its emergence in the different ecozones. permanent research stations were developed in rain forests and savannas to detect virus circulation in vectors and hosts from the tree canopies to the savanna ground. year-round mosquito and monkey sampling over a period of more than years made possible the detection of yfv in various monkey and mosquito species (e.g., aedes africanus, aedes opok, aedes furcifer-taylori, and aedes luteocephalus), thus elucidating the mechanism of yfv maintenance in nature. epidemiological observations during this period allowed max germain to formulate the concept of a "yellow fever zone of emergence" in west and central africa [ ] . these ecological transition zones constitute ecotones adjacent to sylvatic environments, where prevailing ecological conditions, such as vector abundance, presence of non-human primates, and closeness for human contact, enable the cross-species transmission of viruses into humans-a "zone of emergence", which clearly appeared as the main source of epidemics in west africa [ ] . thus, this specific ecosystem constitutes an ideal transition ecotype, where vaccination campaigns for the containment of epizootics and ultimately eradication ought to concentrate [ ] . lastly, virus isolation in male mosquitoes (ae. furcifer-taylori) allowed the documentation of vertical transmission, allowing for virus maintenance in the inter-epidemic periods [ ] . in the early s, research laboratories focusing broadly on arboviruses were established under the umbrella of the collaborating center for reference and research on arboviruses (crora), led by paul brés. crora laboratories were created at various ips throughout africa, including ipd, ipa, and ipb, as well as ip yaoundé (cameroon), and ip tananarive (madagascar). one of the major activities was to establish an inventory of arboviruses circulating in various ecosystems. although virus isolations were made at various ips, virus characterization and identification were carried out at the crora reference center at ipd, followed by confirmation at yaru, with final registration in the international arbovirus catalogue [ ] . at the end of the s, following an outbreak of the ebola epidemic in zaire in , ipb set up a research program on viral hemorrhagic fevers that lasted until [ ] . this research program was the result of an important collaboration between the various pasteur institutes in africa and researchers of orstom. in , orstom extended its field of research and expertise to tropical medical virology, thus supporting teams from the riip. the partnership between riip and ostrom was instrumental in expanding the scope of field research in africa, with seminal studies on the vertical transmission of arboviruses in mosquitoes [ ] or the role of environmental factors, such as climate and latitude, in arbovirus transmission from arthropod to vertebrate hosts, using yfv [ , ] and dengue virus (denv) [ ] [ ] [ ] as models. research at ipb was also critical in elucidating the etiology of exanthematous fevers, coined "congolese red fevers", that have long been attributed to rickettsia. a total of arboviruses (chikungunya, igbo-ora, o'nyong nyong, sindbis, bouboui, yellow fever, wesselsbron, west nile, zika, ilesha, bwamba, dugbe, tataguine, nyando, bangui, and rift valley fever viruses) were associated with these syndromes. symptoms, consisting of fever, diffuse pain, and exanthem, were present in more than % of the cases, with etiology dominated by four viruses-chikungunya, ilesha, bwamba, and tataguine [ , ] . between and , two field research stations were established in the central african republic, one located adjacent to the forest (bouboui) and the other in the wooded savanna (bozo) (figure ). during this period, more than , mosquitoes of identified species in , pools were preserved for virus isolation. the most common anthropophilic mosquitoes caught were aedes (stegomiya) africanus and ae. (st.) opok, inside the forest gallery, aedes vittatus, in the savannah, and anopheles gambiae and an. funestus, in the houses of the village of bozo. a total of viruses were isolated and assigned to different species. these included chikungunya, bagaza, bouboui, bozo, bwamba, ilesha, kamese, kedougou, middleburg, mossuril, m'poko, nyando, orungo, pata, pongola, simbu, sindbis, tataguine, wesselsbron, west nile, yellow fever, and zika viruses. altogether, six arboviruses were found in the forest gallery, including bouboui, bozo, chikungunya, orungo, yellow fever, and zika viruses, vectored primarily by ae. africanus. research at ipd and ipb was also instrumental in demonstrating the expanded range of the crimean-congo hemorrhagic fever virus (cchv) in west and central africa [ ] [ ] [ ] , followed by repeated isolation of the virus. this allowed a clear understanding of its eco-epidemiology in the region, including north-south migration of the infected ticks through the cattle traffic migration patterns in the sahel [ , ] . likewise, active circulation of the rift valley fever virus (rvfv) was also demonstrated in senegal [ ] , mauritania [ ] , upper volta (present day burkina faso) [ , ] , and the central african republic [ ] . support for riip laboratories located in africa was provided by the ipp and ostrom teams, as well as through collaboration with various research centers in the u.s., such as harvard university, supporting the initial study on yellow fever and fnv vaccine; yaru, as a partner for new arbovirus classification; the centers for diseases control (cdc) at fort collins colorado, for the study of arboviruses; the cdc in atlanta and the u.s. army medical research institute of infectious diseases (usamriid), for the initiation of viral hemorrhagic fever research in central and west africa. the era of virus discovery in australia can be traced to the summer of - , when a major epidemic of encephalitis swept through southeastern australia. there were clinical cases reported in victoria, new south wales, and south australia, of which ( %) were fatal [ ] . a similar epidemic of unknown etiology (named australian x disease) had occurred in eastern australia from until , with almost reported cases and an average case/fatality rate of % [ , ] . surprisingly, no further cases were reported in the intervening years. amongst those investigating the - epidemic were john a.r. miles and colleagues at the institute of medical and veterinary science in adelaide, and eric l. french of the walter and elisa hall institute of medical research in melbourne who, almost simultaneously, reported the isolation of a virus from the brain tissue of clinical cases [ , ] . the virus, named murray valley encephalitis virus (mvev), was shown to be closely antigenically related to japanese encephalitis virus (jev), a flavivirus (then designated group b arbovirus) known to cause fatal encephalitis in east and southeast asia [ ] . the subsequent development of arbovirology and the pathway to virus discovery in australia were linked intimately with the establishment of the queensland institute of medical research (now the qimr-berghofer institute) at herston in brisbane ( figure ). ralph l. doherty joined the staff and, in , established a program of virus isolation from mosquitoes, based at a field station at innisfail in the far north queensland. in , doherty isolated the ross river virus (rrv) from aedes vigilax mosquitoes collected in townsville [ ] . he subsequently showed that rrv neutralizing antibodies occurred commonly in human sera in eastern australia [ ] . he also showed that individuals suffering from a severe debilitating syndrome, known as epidemic polyarthritis, had high antibody titres to rrv, suggesting a causal relationship [ , ] . in , doherty and his colleagues isolated the virus from a boy from the edward river mission aboriginal settlement in cape york [ ] . rrv and the related alphavirus, the barmah forest virus (see below), are now recognized as important public health problems in much of australia and the pacific islands, causing arthritis, myalgia, and fatigue for six months or longer. several thousand cases of the disease are notified annually [ ] . , normanton, and cairns in far north queensland. these included four novel flaviviruses (kunjin, kokobera, edge hill, and stratford), three orthobunyaviruses (koongol, wongal, and maputta) and one orbivirus (corriparta) [ ] . the study also identified two alphaviruses previously unknown in australia (sindbis and getah) and the first isolations of mvev from mosquitoes [ ] . with support from the rockefeller foundation, a field station was established at kowanyama and further expeditions were undertaken to collect arthropods and potential mammalian hosts throughout queensland. anopheline mosquitoes and a swamp pheasant (centropus phasianinus) collected at kowanyama from to yielded three novel viruses (kowanyama, trubanaman, and alfuy viruses) [ ] . in - , three novel viruses were isolated at kowanyama (wongorr and mitchell river viruses from mosquitoes and the ngaingan virus from biting midges), three novel viruses were isolated from mosquitoes collected near charleville in western queensland (charleville, warrego, and wallal viruses) and two viruses (belmont and d'aguilar viruses) were isolated from mosquitoes and biting midges, respectively, collected near brisbane [ , ] . further expeditions to charleville to collect mosquitoes resulted in the isolation of two novel viruses in (facey's paddock and murweh viruses) and two novel viruses in (parker's farm and little sussex viruses) [ ] . leanyer virus was also isolated in from mosquitoes collected near darwin in the northern territory [ ] . viruses were also isolated from wildlife hosts; the almpiwar virus was isolated from a skink (cryptoblepharus virgatus) at kowanyama in [ ] and the mossman virus was first isolated from a rodent (rattus leucopus) captured near mossman in [ ] . in collaboration with doherty and his qimr team, expeditions were also conducted to isolate viruses from ticks associated with sea birds. in , harald n. johnson from yaru collected soft ticks (ornithodoros capensis) from sooty tern (onychoprion fuscatus) colonies on the great barrier reef near cairns, from which two viruses (upolu and johnston atoll viruses) were isolated [ ] . the saumarez reef virus was subsequently isolated by toby d. st. george and colleagues from australia's commonwealth scientific and industrial research organization (csiro) in , from the same species of ticks associated with sooty terns on a coral cay in the southern coral sea [ ] . in , m. durno murray from csiro undertook an expedition to the australian territory of macquarie island in the southern ocean to collect hard ticks (ixodes uriae) associated with sea birds, resulting in the isolation of two novel viruses (nugget and taggert viruses) [ ] . a second csiro expedition to macquarie island in yielded two additional novel viruses (gadget's gully and precarious point viruses) from hard ticks collected in royal penguin (eudyptes chrysolophus schlegeli) rookeries [ ] . other research groups in australia also joined the hunt for arboviruses during the late s and early s, including ian d. marshall at the australian national university in canberra and neville f. stanley at the university of western australia. from to , marshall and his colleagues conducted surveys for arbovirus activity, particularly rrv and mvev, in coastal regions of new south wales and in the murray river valley. in addition to these and other known arboviruses, marshall and colleagues isolated several novel arboviruses from mosquitoes, including gan gan, yacaaba, tilligerry and termeil, paroo river, picola, and barmah forest viruses [ , ] and a novel reovirus, nelson bay virus, from a fruit bat (pteropus poliocephalus) [ ] . like the related alphavirus rrv, the barmah forest virus was subsequently shown to be a cause of epidemic polyarthritis in humans [ , ] , with infections occurring commonly throughout australia [ ] . the gan gan virus also infects humans and is suspected of an association with epidemic polyarthritis [ ] . marshall also conducted a number of collecting trips to papua new guinea from to funded by the rockefeller foundation. during an expedition to the sepik river district of papua new guinea in - , he isolated the joinjakaka virus from a mixed pool of culicine mosquitoes and the japanaut virus from both culicine mosquitoes and a fruit bat (syconycteris crassa). in western australia, stanley and colleagues surveyed for arbovirus activity in the ord river valley from to [ , ] . from , mosquitoes of species, virus isolates were recovered, including isolates of mvev and isolates of the kunjin virus from cx. annulirostris, suggesting the region may be an endemic focus in australia [ ] . the study also identified eight novel viruses, including kimberly, parry's creek, ord river, and kunnanurra viruses, as well as four unknown isolates (or , or , or , and or ), which have yet to be characterized [ , ] . continuing surveillance in western australia by others has continued to reveal novel arboviruses, including oak vale, stretch lagoon, parry's lagoon, and fitzroy river viruses [ ] [ ] [ ] [ ] . in , csiro established a new virology laboratory at long pocket in brisbane, headed by toby d. st. george, to investigate endemic diseases of livestock in northern australia. in , doherty and colleagues had isolated bovine ephemeral fever virus (befv) from cattle during a major epizootic in queensland [ ] but, despite epidemiological evidence suggesting vector-borne transmission, the virus had never been isolated from insects. this led st. george and colleagues to attempt virus isolations from a location in northern australia, where serological monitoring of a sentinel herd of cattle indicated that befv was likely to be enzootic. for a continuous period from october until may , insect collections for virus isolation were conducted at beatrice hill southeast of darwin. from the , mosquitoes and , biting midges processed, one isolate of befv was recovered (from a mosquito pool). however, the collection also yielded other virus isolates from different serological groups, including four novel viruses (csiro village, marrakai, beatrice hill, and humpty doo virus) [ ] . most significantly, the collection also yielded a single isolate of a novel serotype of bluetongue virus (btv serotype , btv- ), a major pathogen of sheep and goats that had previously been regarded as exotic to australia [ ] . the isolation of btv- and the consequences for international trade dramatically changed the landscape with respect to virus discovery and characterization in australia. an immediate consequence was the approval of government expenditure for the establishment of the $ million csiro australian animal health laboratory (aahl) in geelong, victoria, providing high-level biosecure containment for laboratory work and live animal studies. the discovery also led to the establishment of a permanent veterinary virology capability at the berrimah veterinary laboratory in darwin under geoff p. gard, and a national program for serological monitoring of sentinel cattle herds and the collection of insect vectors. efforts to isolate viruses from arthropods and livestock intensified. in the northern territory, a second novel serotype of bluetongue virus (btv- ) was isolated from a healthy sentinel cow at victoria river station in [ ] , and four other novel arboviruses (coastal plains, berrimah, adelaide river, and koolpinyah viruses) were isolated from healthy cattle between and [ ] [ ] [ ] [ ] . in queensland, eight novel arboviruses were first isolated between and from biting midges (tibrogargan, tinaroo, peaton, wongabel, and walkabout creek viruses), healthy sentinel cattle (the douglas virus), and soft ticks (argas robertsi) (vinegar hill and lake clarendon viruses) [ , [ ] [ ] [ ] [ ] [ ] . surveillance activities by the berrimah veterinary laboratory have continued to the present, with regular reports of the isolation of novel arboviruses. continuing surveillance by others in northern australia has also resulted in the isolation from mosquitoes of the bamaga virus and new mapoon virus from cape york [ , ] . the s also saw several significant disease emergence events in australia, which drew particular attention to bats as reservoir hosts of highly pathogenic viruses. in september , an outbreak of a severe respiratory disease occurred in horses at a stable in brisbane. of the affected horses were euthanized or died of the disease. one of two severely affected humans who had contact with the horses also died. cooperation between the queensland government, the newly established csiro australian animal health laboratory, and others resulted in rapid isolation of the hendra virus, a novel paramyxovirus [ ] , and the identification of fruit bats as reservoir hosts [ , ] . the hendra virus has since re-emerged regularly in australia, with more than confirmed cases in horses and seven infected humans, four of whom have died. in , an injured female fruit bat (pteropus alecto) was found at ballina in new south wales. tissue homogenates from the euthanized bat were injected into mice, resulting in the isolation of a novel lyssavirus, subsequently named australian bat lyssavirus (ablv) [ ] . three fatal human cases of ablv infection have subsequently been reported [ ] [ ] [ ] . the virus is now known to occur at low prevalence in five of six families of bats endemic to the northern territory, queensland, and western australia [ ] . in april , another novel paramyxovirus, the menangle virus, emerged at a commercial piggery in new south wales, causing stillbirths with abnormalities of the brain, spinal cord, and skeleton [ ] . two humans exposed to the pigs also developed an influenza-like illness [ ] . fruit bats were again implicated as reservoir hosts [ ] . the role of bats in the ecology and emergence of pathogenic viruses has been a major focus of study in australia since that time, primarily involving research teams led by hume e. filed and linfa wang. in all, more than novel rna viruses representing families and genera have been isolated from humans, livestock, wildlife, and arthropods in australia and papua new guinea, and reported in the literature (table s ). many others have been isolated but remain uncharacterized and/or unreported. more complete characterization of these viruses will be facilitated greatly by the use of ngs. south and southeast asia have also been a fertile area for virus discovery, particularly novel mosquito-borne and tick-borne flaviviruses and viruses with reservoirs in bat species. early studies in india, partly funded by the rockefeller foundation, by telford work and his indian colleagues from the virus research centre in pune, including d.p. murthy, p.n. bhatt, h. trapido and k. pavri, led to the discovery of the kyasanur forest disease (kfd) virus [ ] . the virus was isolated from sera and tissues collected from a moribund black-faced langur (presbytis entellus). this followed reports of an epizootic of unknown etiology causing large numbers of deaths in non-human primates and a number of cases of severe febrile illness in villages close to forested areas where dead monkeys had been found. the virus was shown to be closely related to the russian spring-summer encephalitis (rsse) serocomplex of flaviviruses, now known as the tick-borne encephalitis (tbe) serocomplex of flaviviruses. the virus was also isolated from some larvae and nymphs of hemaphysalis spinigera ticks [ ] . kfd in humans followed a biphasic course, not unlike tbe, but with some hemorrhagic manifestations not seen in tbe, and without either meningitis or encephalitis. another tick-borne virus related to the rsse serocomplex, langat virus, had been isolated two years earlier from a pool of hard ticks, ixodes granualtus, collected from forest rats caught near kuala lumpur, malaysia, by c.e. gordon smith, then working at the institute for medical research in kuala lumpur [ ] , but it is not known to be a human pathogen. a number of mosquito-borne flaviviruses were first isolated in southeast asia. the most important with respect to human disease are three of the four dengue serotypes. although dengue serotype had been first isolated independently by hotta in japan in [ ] , and shortly after by sabin in cincinnati in with material collected in hawaii [ ] , the other three serotypes were first isolated from material collected in southeast asia. dengue serotype was also isolated by sabin in from material obtained from new guinea [ ] and dengue serotypes and were first isolated in from human sera and aedes aegypti and culex tritaeniorhynchus mosquitoes collected during a major outbreak of epidemic hemorrhagic fever in manila, philippines, by w.m. hammon, a. rudnick, and colleagues at the university of pittsburgh [ ] . other novel flaviviruses have been isolated in malaysia, thailand, and papua new guinea [ ] . the tembusu (tmuv) virus was isolated in kuala lumpur in from various mosquito species [ ] and was the first of several closely related viruses, including the thcar virus, which was isolated from a pool of cx. tritaeniorhynchus mosquitoes collected in chiang mai, thailand, in [ ] ; the sitiawan virus, from sick broiler chicks in malaysia [ ] ; and the duck tembusu virus, an infection of ducks and geese causing an egg-drop syndrome in china and southeast asia [ , ] . neutralising antibodies were found in humans in malaysia [ ] but the virus has not been implicated in human disease. two other mosquito-borne flaviviruses have been described, jugra virus and sepik virus. little is known about the jugra virus, which was isolated from aedes spp. and uranotaenaia spp. mosquitoes and from the blood of a cynopterus brachyotis fruit bat [ ] . the sepik virus was isolated in by ian d. marshall and colleagues from a pool of mansonia septempunctata mosquitoes collected in the sepik district of papua new guinea [ ] . it was associated with a hospitalized case of febrile illness of unknown origin, with rising neutralising antibody to the virus. the sepik virus is particularly interesting, as its nucleotide sequence analysis shows it to be the closest known flavivirus to yellow fever virus [ ] . a novel lineage of the west nile virus was isolated in sarawak, east malaysia, by d.i.h. simpson, e.t.w. bowen, and colleagues, from cx. pseudovishnui group mosquitoes [ ] . initially called kunjin virus, it was shown to differ significantly in genomic sequence from the australian kunjin viruses, which have been shown to comprise west nile lineage b viruses, and have been described as west nile lineage virus [ ] . two flaviviruses with no known vector have been isolated in southeast asia, both from cy. brachyotis fruit bats: the carey island virus was isolated from a bat in the jugra forest, malaysia, in by a. rudnick and colleagues from the institute of medical research, kuala lumpur and the international center for medical research, university of california [ ] , and the phnom penh virus was isolated by j.j. salaun and colleagues in from the salivary glands and brown of bats [ ] . a closely related virus, the batu cave virus, is considered to be a variant of phnom penh virus. a considerable number of novel bunyaviruses have been isolated from south and southeast asia, particularly by scientists from the national institute of virology (formerly the virus research centre) in pune, including p.n. bhatt, k. pavri, k.r. singh, c.n. dandawate, f.m. rodrigues, d.t. mourya, p.d. yadev, a.c. mishra, and many others. recently reviewed in [ ] , these viruses include the orthobunyaviruses, umbre, kaikalur, thimiri, and sathuperi viruses; a nairovirus, ganjam virus; phleboviruses, bhanja, and malsoor viruses; a hantavirus, thottapalayam virus; and two uncharacterized viruses, kaisodi and wanowrie viruses. additionally, novel bunyaviruses, batai and oya viruses, have been isolated in malaysia, the former from cx. gelidus mosquitoes [ ] and the latter from pigs [ ] , and the kaeng khoi virus was isolated from tadarida plicata bats in thailand. novel orbiviruses from south and southeast asia include the sathuvachari virus, isolated from starlings (brahminy myna) collected in vellore, tamil nadu, india, and most closely related to the mosquito-borne orbiviruses [ ] ; and the japanaut virus, isolated from a mixed pool of culicine mosquitoes from papua new guinea [ ] . new rhabdoviruses first isolated in south asia include the chandipura virus and joinjakaka virus-the former, a major human pathogen in india, was isolated from a human infection in near nagpur city [ ] , whereas the latter, isolated in from a mixed culicine pool in the sepik district of papua new guinea, is not associated with disease in humans or animals. chandipura infection is characterized by fever, chills, arthralgia, myalgia, vomiting, and weakness. two novel alphaviruses were reported in kuala lumpur-bebaru and getah viruses. bebaru was first isolated from cx. (lophoceraomyia) spp. collected in , but although neutralising antibodies have been found in human sera, it has not been associated with human disease [ ] . getah virus was first isolated from cx. gelidus mosquitoes collected in near kuala lumpur [ ] . it causes a mild disease in horses, characterized by pyrexia, edema of the hind limbs, swelling of the submandibular lymph nodes, and urticarial rash. it also causes a mild disease in pigs, with occasional reproductive problems, including abortion and neonatal infections. neutralising antibodies have been found in a number of animals and in humans. the important role of bats as reservoirs of a wide range of viruses was underlined by a number of the viruses described above, and particularly by the discovery of their role as the reservoir of the nipah virus in malaysia in [ ] and subsequently their probable role as the origin of severe acute respiratory syndrome coronavirus (sars-cov) [ , ] . the nipah virus, a virus closely related to the hendra virus in australia, was first isolated k.b. chua and s.k. lam during an outbreak of severe disease of humans and pigs in - in peninsula malaysia [ ] , resulting in human cases with a mortality of %, and the culling of over million pigs. transmission to humans was from infected pigs. the disease in humans was a rapidly progressive encephalitic syndrome, with a significant pulmonary syndrome in some patients [ ] . in pigs, the disease was spread via the respiratory tract, and the symptoms were either neural or pulmonary, or both. subsequent epidemics in bangladesh and india have substantially expanded our knowledge of the nipah virus, and have demonstrated that direct transmission of the virus from bats to humans can occur through the consumption of date palm juice, and possibly by other routes, and that mortality rates may often be significantly greater than in malaysia [ ] . furthermore, evidence of nipah-like and hendra-like viruses have been detected either by isolation or serology from other pteropid bats across the geographic range of the genus, and related viruses may be carried by other bat species on other continents. sars-cov was first isolated by m. peiris and colleagues in hong kong [ ] , and contemporaneously in the u.s. [ ] and europe [ ] . it was shown to be unrelated to other coronaviruses. transmission to humans is believed to have been via an intermediate host, such as the himalayan palm civets (paguna larvata), through wet markets in southern china. continued studies of the nipah virus in malaysia, and subsequently in bangladesh and india, and investigations of sars-cov in bats have resulted in an enormous explosion of knowledge of viruses carried by bats, with many examples from most viral families, although in many cases the information is from genomic fragments [ ] . virus isolations have been made from bats, especially frugivorous bats, from india and malaysia. one of the earliest isolations was a paramyxovirus of the genus rubulavirus, which was isolated from a rousettus leschenaultia bat collected near pune in india [ ] . a novel adenovirus from the genus mastadenovirus was also isolated from the same fruit bat species caught in maharashtra state [ ] . a number of viruses have been isolated from fruit bats in malaysia by k.b. chua, s.k. lam, l.f. wang, and their colleagues-tioman virus, a paramyxovirus in the genus rubulavirusi, isolated from pteropus hypermelanus and related to the australian menangle virus, but not known to cause human disease [ ] ; pulau virus, an orthoreovirus related to the nelson bay virus of australia, and not associated with human or animal disease [ ] ; melaka virus, an orthoreovirus, causing acute respiratory disease in humans [ ] ; and kampar virus, an orthoreovirus related to the melaka virus, and also causing acute respiratory disease [ ] . the importance of orthoreoviruses originating in pteropid bats was assessed in an outpatient clinic, where it was found that pteropine orthoreoviruses are among one of the common causative agents of acute upper respiratory tract infection (urti), with a cough and sore throat as the most common presenting clinical features [ ] . the history of arbovirus research in the ussr began in , when an expedition under the leadership of lev a. zilber (at the time, the head of central virological laboratory of narkomzdrav ussr in moscow) went to the russian far east to study seasonal epidemic encephalitis. this disease with high mortality rates affected forest workers and soldiers stationed in the taiga, mainly those who came from other regions of the ussr. the disease had a pronounced seasonality-the cases started being recorded at the beginning of may, reached the peak in early june, and declined by august. local doctors designated the disease "spring-summer encephalitis" (sse) and assumed that it had been caused by some kind of virus. it has also been suggested that there were some similarities between sse and "summer encephalitis" (japanese b encephalitis and st. louis encephalitis) described at the time, it was also assumed to be a toxic form of influenza [ ] . however, the etiology and transmission routes of sse remained unclear. during summer of , zilber and colleagues isolated at least strains of a new virus from the blood and cerebrospinal fluid of sick people, and from brain tissues of dead patients. the isolated virus had a weak antigenic relationship (in complement fixation tests) with japanese b encephalitis virus [ ] . based on comparative analysis of epidemiologic data and the seasonal abundance of ixodes persulcatus ticks in the taiga, zilber assumed that sse was transmitted by ticks, in contrast to "summer encephalitis", which is transmitted by mosquitoes [ ] . several strains of the virus were isolated from the ix. persulcatus ticks, and their ability to transmit the virus by biting laboratory animals was shown experimentally [ ] . one of the first isolated strains (sofjin) was used for infecting rhesus macaques, which developed the clinical symptoms with signs of central nervous system (cns) impairment, similar to those in sick people [ , ] . so, the etiological agent of sse, which was subsequently given the name tick-borne encephalitis, was discovered and is now known by the name tick-borne encephalitis virus (tbev). in - , subsequent expeditions under the leadership of pavlovsky and smorodintsev studied in detail various aspects of the ecology, epidemiology, and pathogenesis of tbev, as well as the protective properties of the first anti-tbe vaccine, obtained from the brain tissue of mice infected by the tbev strain sofjin [ ] [ ] [ ] . further studies showed that tbev is also prevalent in other regions of the ussr, including the european part, where the main vector of the virus is ix. ricinus ticks. at the same time, it was found that tbev is also an etiological agent of some seasonal encephalitis or febrile illnesses, such as central european encephalitis or biphasic milk fever [ ] [ ] [ ] . the strains of tbev were initially divided into two geographical subtypes ("far eastern" and "central european"). these subtypes differed in severity of the illness and had antigenic differences in virus neutralization tests with serum of convalescents [ ] . a third subtype of tbev ("west siberian") was described by pogodina and her colleagues in [ ] . genetic data that has been accumulating since the late s confirms the existence of three main tbev subtypes (or genotypes). the nucleotide difference between genotypes reaches - % when comparing complete genomes [ ] [ ] [ ] . tbe is the most important arboviral infection in russia. despite significant progress in the development of anti-tbev vaccines, thousands of cases are recorded annually in russia, mainly in siberian and far eastern regions [ ] . in the modern classification, tbev belongs to the species tick-borne encephalitis virus of the genus flavivirus (flaviviridae) [ ] . tbev is widely distributed within the area of its main arthropod vector-ix. persulcatus and ix. ricinus ticks, including russia, eastern and central europe, baltic and scandinavian countries [ , ] . the discovery of tbev as a causative agent of sse gave an impetus to studies of similar diseases throughout the ussr. during subsequent years, the major virological centres were established as parts of the academy of medical science of the ussr (ams ussr), such as the department of neurovirology at the institute of neurology ( ), the institute of virology ( ), the institute of poliomyelitis and viral encephalitis ( ), as well as departments of virology at regional medical institutes in siberia and the far east. scientists from these centres were actively involved in the study of various zoonotic viral infections distributed in the ussr. many participants of the first expeditions subsequently became famous virologists. one of the most notable ones is michael p. chumakov, who later headed the institute of virology ams ussr ( ) ( ) ( ) ( ) ( ) and the institute of poliomyelitis and viral encephalitis ams ussr ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) in moscow. chumakov organized numerous expeditions that aimed to study the etiology of zoonotic human infections. in the s, outbreaks of the disease, designated by local doctors as "atypical tularemia", "anicteric leptospirosis", and "omsk spring-summer fever", were recorded in several rural regions of the omsk district in western siberia. clinicians from the omsk medical institute, under the leadership of ahrem-akhremovich, described the disease in detail and named it omsk hemorrhagic fever (ohf), as the patients often developed hemorrhagic diathesis. they also suggested that ohf was transmitted by dermacentor reticulates ticks, which are highly prevalent in the region [ , ] . in , chumakov and colleagues investigated the blood of patients with ohf and isolated strains of a new virus, which was similar but different from tbev in serologic tests. the virus was named omsk hemorrhagic fever virus (ohfv). several strains of ohfv were also isolated from de. reticulates ticks collected in the natural foci of ohf [ , ] . in subsequent years, the ecology of ohfv was extensively studied by scientists from the omsk medical institute and the institute of poliomyelitis and viral encephalitis ams ussr. the de. reticulatus ticks and their host, a narrow-headed vole (microtus gregalis), are considered an original natural reservoir of ohfv. the european water vole (arvicola amphibius), the tundra vole (microtus oeconomus), and some species of shrews are also involved in the circulation of ohfv [ ] . however, the emergence of ohf outbreaks in the s was presumably a consequence of the introduction by humans of muskrats (ondatra zibethicus) to this region in - [ ] . muskrats are highly susceptible to ohfv and serve as an extremely effective amplifying host. the appearance and growth of the muskrat population in the natural foci of ohf led to an increase in infection rates in other animals and ticks [ , ] . in addition to transmission of ohfv by ticks, humans can get infected while hunting and skinning, by direct contact with blood and excretions of infected animals. such "muskrat outbreaks" among hunters and their family members have been registered in the region at different times of the year, including winter, which is the season of active hunting for muskrats [ , ] . based on antigenic relationships, ohfv was assigned to the tbe antigenic complex [ ] , and later was classified as a separate species, omsk hemorrhagic fever virus of the genus flavivirus (family flaviviridae) [ ] . genome sequence analysis confirmed the close evolutionary relationships of ohfv with tbev [ ] [ ] [ ] . in , virologists led by chumakov studied the etiology of an outbreak of a febrile illness which was accompanied with hemorrhagic manifestations ("acute infectious capillary toxicoses") in a rural area in the northwest part of the crimean peninsula. they designated the disease as crimean hemorrhagic fever (chf) and suggested that is transmitted by hyalomma (plumbeum) marginatum ticks. despite the absence of virus isolates from specimens from chf patients or from ticks, the viral etiology of chf and its zoonotic nature were proven experimentally by infecting volunteers with the blood of chf patients or a filtered suspension of ticks collected from a hare caught in the focus of the disease [ ] . sporadic cases and outbreaks of chf were subsequently recorded almost annually in southern regions of the european ussr and central asian soviet republics. the first strains of the chf virus were isolated by alexander m. butenko from chumakov's team in , from sera of chf patients and from hy. marginatum nymphs isolated in southern russia [ , ] . later, the chf virus was shown to be identical to the congo virus isolated from a patient with hemorrhagic fever in zaire (present day democratic republic of congo) and the virus received its present name, the crimean-congo hemorrhagic fever virus (cchfv) [ ] . cchfv is a one of the prototypic nairoviruses and today is assigned to the species crimean-congo hemorrhagic fever virus, of the genus orthonairovirus (nairoviridae: bunyavirales). during spring and summer , chumakov, together with libíková from the institute of virology in bratislava (former cžechoslovakia), investigated an outbreak of fibrile illness in the kemerovo district in western siberia. initially, it was assumed that the patients were affected by tbe, but the sera of the patients did not react with tbev-specific antigen in serological tests. on the contrary, a new virus, named the kemerovo virus (kemv), was isolated from the blood of patients. several strains of kemv were also isolated from ix. persulcatus ticks collected in the region where the outbreak occurred [ , ] . similar to kemv, the tribeč virus and lipovníc virus were isolated from ix. ricinus ticks in czechoslovakia in [ , ] . based on morphological studies, kemv was classified to the genus orbivirus (family reoviridae) [ ] . the ecology of kemv in russia has not been studied sufficiently, but recent research has shown that its prevalence in ix. persulcatus, ix. ricinus, ix. pavlovsky, and de. reticulatus ticks varies from zero to . % in different regions of the country [ , ] . from the above, it follows that in the period - , arboviruses in the ussr were studied mostly as causative agents of human disease. examinations of arthropods and vertebrates in the natural foci of important human disease often led to exploring some other arboviruses. for example, butenko isolated the west nile virus (wnv) and dhori virus (dhov) from hy. marginatum ticks for the first time in the ussr while studying the natural foci of cchfv in the southern region of russia in [ ] . in the late s, there was an ecological trend in virology developing in the ussr. the founder of the ecological approach to virology in the ussr was dmitry k. lvov, who established the department of the ecology of viruses at the d.i. ivanovsky institute of virology in moscow ( ) , and later headed the institute ( - ). under his leadership, an ecological and virological survey was organized, aimed to identify the arboviral diversity in hematophagous arthropods and wild animals of the entire ussr. the survey included collecting and examining mosquitoes, ticks, and vertebrate animals (mostly rodents and birds), as well as samples from humans, in different types of biocenoses located in different climatic zones of the ussr. lvov and colleagues isolated more than strains of different mosquito-borne viruses, including viruses of the california encephalitis antigenic group (species california encephalitis orthobunyavirus) and batai and batai-like viruses (species bunyamwera orthobunyavirus) in the genus orthobunyavirus, family peribunyaviridae [ ] [ ] [ ] [ ] . the other mosquito-borne viruses whose circulation was discovered and studied extensively, are the sindbis virus (sinv) and getah virus (getv) (genus alphavirus, family togaviridae) [ ] [ ] [ ] . one of the important subjects of d. lvov's research was ix. uriae ticks, which parasitize on colony-nesting sea birds. in - , more than virus strains were isolated from ix. uriae ticks collected in the nests of sea birds on the coasts and islands in the sea of okhotsk, the bering sea, and the barents sea [ ] . the isolated strains were mostly classified as novel bunyaviruses, flaviviruses, and orbiviruses, often based on morphological studies of the virion structure only, because their antigenic relationships with other viruses were not known at the time. among them, the sakhalin virus (sakhv) and paramushir virus (prv) were described as a novel bunyaviruses and later classified to the species sakhalin orthonairovirus (genus orthonairovirus, family nairoviridae) [ ] . several other new viruses (zaliv terpenia, comandory, and rucutama viruses) were discovered and now belong to the species uukuniemi phlebovirus (genus phlebovirus, family phenuiviridae) [ ] . the tyuleniy virus (tyuv) was isolated for the first time, which is one of the prototypic viruses of seabird tick-borne flaviviruses group (genus flavivirus, family flaviviridae) [ ] . the prevalence of the okhotsky virus (okhv) and aniva virus (aniv), two newly described viruses belonging to the species great island virus (genus orbivirus, family reoviridae), have been studied in detail [ , , ] . many new viruses were discovered by lvov and his colleagues while exploring the territories of central asia and transcaucasia. they isolated and studied the issyk-kul virus (iskv), which is associated with bats of the family vespertionidae and their argasid ticks [ , ] . new viruses, tamdy (tamv) and burana (burv), were isolated from hyalomma spp. ticks collected from sheep or cows in pasture lands [ ] . some novel viruses (artashat, chim, and geran viruses) were isolated from argasid ticks collected in rodent burrows [ ] . morphological studies of these viruses by electron microscopy identified them as bunyaviruses. recently, they were classified as different species of the genus orthonairovirus (family nairoviridae) [ ] . in total, during the ecological and virological surveys of the s to s, thousands of strains of different arboviruses were isolated, some of which remain to be classified. based on the studies conducted by soviet and russian virologists, we now know that at least zoonotic viruses, assigned to eight viral families, circulate on the territories of the former ussr [ ] . does this number reflect the true diversity of viruses circulating in the vast territory of northern eurasia? this question can only be answered by additional research aimed at finding new viruses, using new methods and approaches. the concept of viruses developed from the observations of ivanovsky and beijerinck of "filterable agents", with the discovery of the causative agent of tobacco mosaic in the s. yellow fever virus and dengue virus were the first two arboviruses to be isolated early in the th century [ , ] . the pioneering work of alexis carrel on the development of many cell and tissue culture methods in the s at the rockefeller institute, and later refinements by maitland, eagle, and enders, led to the widespread use of various culture systems as indispensable tools for virus studies [ ] [ ] [ ] . although these tools have since been used extensively for the in vitro characterization of viruses, they were inadequate for the identification and classification of a flood of novel viruses collected through the yfv surveillance program supported by the rockefeller foundation. jordi casals, among others, led the use of the complement fixation (cf) test in order to study viruses affecting the central nervous system. the cf test exploits the unique affinity of complement for antigen-antibody complexes. the original assay was developed in the s for the serologic study of yfv, was improved in the s [ , ] , and its sensitivity and specificity improved again in the s [ ] . using cf tests, casals and his colleagues were able to classify viruses into antigenic groups. however, the inherent complexity and labour consuming aspects of the assay (titrations of antigen, complement, and hemolysin for optimal outcomes), technical demands (accurate interpretation of outcomes) and the development of alternative assays (see below), have restricted its applicability in laboratories worldwide. hirst observed in that chicken erythrocytes agglutinated in the presence of the influenza a virus and that virus-specific antibodies inhibited agglutination, forming the foundation for the hemagglutination inhibition (hi) test [ ] . a decade later and on theiler's suggestion, casals showed that many arboviruses also agglutinated erythrocytes, establishing the hi test as a diagnostic tool for arbovirus infection and identification [ ] . the gold standard for arbovirus identification, the plaque reduction neutralization test (prnt), has its origins in the observations of stokes and colleagues, dating back in the s when monkeys could be protected against yfv by the inoculation of convalescent sera from patients who had recovered from the disease [ ] . by the early s, max theiler had adapted the assay for use in mice, in which mixed serum and virus was inoculated intracerebrally [ ] . the cell culture adaptation of the test was first demonstrated by itoh and melnick in for studying the seroconversion of chimpanzees infected with echoviruses [ ] , and a year later by henderson and taylor to detect antibodies to the eastern equine encephalitis virus [ ] . versions of this assay are now widely used, including the microprnt [ ] , the virus reduction neutralization test (vrnt) [ ] , the focus reduction neutralization test (frnt) [ ] , the rapid fluorescent inhibition test (rffit) [ ] , the flow-cytometry neutralization [ , ] , the colorimetric micro-neutralization assay (cmnt) [ ] , and the reporter virus particle-based neutralization assays [ ] [ ] [ ] [ ] . historically, these methods (virus isolation, hi, cf, and neutralization tests) served as the basis of arbovirus diagnosis for many years, augmenting electron microscopy (see section below), which allowed the visualization of viruses in infected tissues and cell cultures. however, an inherent limitation of the serology-based assays has been their inability to determine whether antibodies in the examined serum were the result of a recent or past infection. this conundrum was solved by determining whether antibodies were igm (recent infection) or igg (past infection), using the enzyme-linked immunosorbent assay (elisa) [ ] . the introduction of elisa revolutionized the field by also offering increased specificity and sensitivity for the accurate detection of many viruses. overall, although identification of pathologic agents through serologic assays is quite straightforward, there are instances where accurate identification may not be possible due to cross-reactivity. for example, cross-reactivity among flaviviruses poses a challenge in their identification, even when the "gold standard" of prnt for arbovirus detection is applied, especially in hyper-endemic settings of flavivirus circulation. several diagnostic labs faced this challenge during the recent emergence and explosive spread of the zika virus in the americas. a similar challenge is also common for the serologic diagnosis of bunyavirus infections, which is attributed to their ability to reassort. in this scenario, a novel bunyavirus may be misidentified as a known pathogen due to the presence of the m segment (contributed by the known pathogen), which encodes the immune-reactive envelope proteins (reviewed in [ ] ). since the beginning of modern virology in the s, transmission electron microscopy (tem) has been one of the most important and widely used techniques for the identification and characterization of new viruses. two tem techniques are usually used for this purpose: negative staining on an electron microscopic grid coated with a support film and (ultra) thin section tem of infected cells, fixed, pelleted, dehydrated, and embedded in epoxy plastic. negative staining can be conducted on highly concentrated suspensions of purified virus or cell culture supernatants. for some viruses, tem can be conducted on contents of skin lesions (e.g., poxviruses and herpesviruses) or concentrated stool material (rotaviruses and noroviruses). for successful detection of viruses in ultrathin sections of infected cells, at least % of cells must be infected, and so either high multiplicity of infection (moi) or rapid virus multiplication is required. viruses can be differentiated by their specific morphology (ultrastructure): shape, size, intracellular location or, for some viruses, from the ultrastructural cytopathology and specific structures forming in the host cell during virus replication. usually, ultrastructural characteristics are sufficient for the identification of a virus at the level of a family. in certain cases, confirmation can be obtained by immuno-em performed either on virus suspension before negative staining or on ultrathin sections. this requires virus-specific primary antibodies, which might be not available in the case of a novel virus. for on-section immuno-em, oso post-fixation must be omitted and the partially dehydrated sample must be embedded in a water-miscible acrylic plastic (usually lr white). the ultrastructure of most common viruses is well documented in good atlases and book chapters [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and many classical publications of the s, s, and s. several excellent reviews were recently published on the use of tem in the detection and identification of viruses [ ] [ ] [ ] . the advent of next generation sequencing (ngs) has expanded the tool kit of the virus hunter. for many years, sanger-based sequence analysis has been employed in the identification and characterization of viruses [ ] [ ] [ ] [ ] . however, with the completion of the human genome sequence, the necessity for a high throughput approach that provided a massively-parallel sequencing strategy was fully apparent [ , ] . the automated sanger method was considered a first-generation technology and newer methods are referred to as next generation sequencing (ngs). commercially available technologies from roche/ , illumina, life technologies/apg, oxford nanopore, and pacific biosciences offer unique ngs platforms, and all have been extensively reviewed [ ] [ ] [ ] [ ] [ ] . unlike sanger sequencing, ngs does not require prior knowledge of the viral sequence and thus can be used for viruses of unknown sequence. many viruses cannot be cultured in the cell culture systems currently in use. ngs has shifted the paradigm by removing the need for cell culture and so opening the door to the discovery of many new viruses. the first instruments for ngs were developed in the s and commercialized in the early s, and they were quickly adopted for the identification of novel viruses from a wide range of sources. the number of known viruses increased from about , in to approximately , viruses in [ ] , and that number has since increased dramatically. the technology has also been applied to sequence analysis of many previously known but poorly characterized viruses. this has significantly expanded the known virosphere and assisted in understanding the diversity and evolutionary relationships of viruses. the expansion of the known virosphere has also allowed the taxonomic assignment of an increasing number of viruses, with a total of orders, families, genera, and species of viruses currently approved by the international committee on taxonomy of viruses (ictv) [ ] [ ] [ ] [ ] [ ] [ ] . ngs has also allowed sequence analysis of hundreds or thousands of isolates known pathogenic viruses, facilitating epidemiological studies at scales extending from very local to global. this has generated a trove of new knowledge of significant public health importance. however, without the availability of isolates, ngs has not necessarily increased our understanding of the ecology of novel viruses, their host range, and the risks they may pose to public, veterinary, agricultural, or environmental health. the application of ngs to the unbiased mass sequencing and bioinformatic analysis of total nucleic acids extracted from biological samples obtained from a wide range of sources has led to an explosive increase in the number of complete or near-complete viral genomes. for example, a recent study using ngs to sequence the transcriptomes of arthropods representing species from four classes (insecta, arachnida, chilopoda, and malacostraca) identified novel viruses, many of which are represented by complete or near-complete genomes [ ] . the novel viruses encompass the entire taxonomic diversity of previously known families and/or genera of (-) ssrna viruses and include divergent viruses with entirely novel and unusual genome architecture. similarly, sequence analysis of the transcriptomes of animals of more than species sampled across nine metazoan phyla (arthropoda, annelida, sipuncula, mollusca, nematoda, platyhelminthes, cnidaria, and echinodermata), as well as chordates of the subphylum tunicata (salps and sea squirts), resulted in the discovery of rna viruses, mostly represented by complete or near-complete genomes [ ] . based on phylogenetic analysis of rna polymerase (rdrp) domain sequences, the novel viruses included clades representing many established families of plant and animal rna viruses, as well as at least five clades that are so divergent that they are considered as likely new virus families or orders. also, the sequencing of transcriptomes of gut, liver, and lung or gill tissue of fish, reptiles, amphibians, and birds identified novel vertebrate-associated viruses, representing every family or genus of rna virus associated with vertebrate infection, including those containing important human pathogens (orthomyxoviruses, arenaviruses, and filoviruses) [ ] . these and other similar studies have heralded a new era in virology, revealing new dimensions in viral biodiversity and providing largely unexpected insights into the deep evolutionary history of viruses. however, only a minor subset of newly discovered viruses has been subject to full phenotypic characterization which can provide critical and fundamental insights into their biology and virus-host interactions, ultimately transforming our understanding of the evolutionary forces that shape the virosphere and disease emergence. realistically, as important as these discoveries are to the advancement of science, very few of the viruses will ever cause human disease or influence the global economy. this mass sequencing approach, which has been called viral metagenomics, can also be applied in a more targeted way to identify viruses in clinical cases of diseases of unknown etiology or to survey for potentially novel zoonotic viruses that may represent a significant risk of transmission to humans. indeed, ngs is being used increasingly in conjunction with real-time pcr as a front-line tool in medical and veterinary settings for rapid detection and identification of exotic or unknown emerging viruses. for example, in , an outbreak of acute hemorrhagic fever occurred in mangala, democratic republic of congo (drc), involving three human cases, two of which were fatal. as no positive diagnosis was obtained using real-time pcr for known viral hemorrhagic fevers in africa, ngs was conducted on acute phase serum collected from the surviving patient, revealing the near-complete sequence of a novel rhabdovirus, bas-congo virus (basv; species bas congo tibrovirus) [ ] . although the disease was attributed by the investigators to the novel virus, no isolate was obtained and there was no evidence of neutralising antibodies in serum samples from undiagnosed hemorrhagic fever cases or random serum donors from the drc. subsequently, ngs of blood collected from healthy individuals from nigeria identified two related viruses, ekpoma virus (ekv- ; species ekpoma tibrovirus) and ekpoma virus (ekv- ; species ekpoma tibrovirus), and a serological survey indicated that antibodies to these or similar viruses occur commonly in healthy humans in nigeria [ ] . however, once again, neither virus was isolated. interestingly, several other tibroviruses had previously been isolated from healthy cattle or biting midges (culicoides spp.) in australia and florida [ , , , ] . none have been associated with either disease in livestock or the infection of humans [ , ] . these and other studies raise important issues regarding the significance of ngs data, even when providing complete or near-complete viral genome sequences, when investigating disease etiology. most viruses can cause asymptomatic infections and many newly discovered viruses may be benign in their natural host. therefore, in the absence of a virus isolate which can be used for experimental studies, establishing a causal association with disease based only on detection of the viral genome should be approached cautiously. the availability of a rapidly expanding number of novel viral genomes identified by metagenomic studies has also presented challenges for virus taxonomy-a system for classification of viruses that is administered by the international committee on taxonomy of viruses (ictv). should viruses detected only by their nucleotide sequence be classified and assigned to species and other higher taxa (genus, family order, etc.) alongside viruses for which we have a viable isolate? the ictv (then the international committee on nomenclature of viruses) was established in at the ninth international congress for microbiology in moscow, publishing its first report in [ ] . it operates under the auspices of the international union of microbiological societies (iums), with the authority to develop, refine, and maintain a universal virus taxonomy. historically, the description and classification of a new virus by the ictv required significant information, such as host range, serology, replication cycles, and structure, aspects that could be determined from the study of isolates. on the other hand, sequences alone provide a trove of information, including evolutionary relationships (e.g., phylogeny), genome organization (e.g., the number of genes and their order), presence or absence of distinctive motifs (e.g., protein cleavage sites, terminal sequences, internal ribosome entry sites), as well as genome composition (e.g., codon usage, gc content), which of course could be used to inform classification into species. these concerns framed the contents of a workshop of experts and members of the ictv, resulting in a seminal consensus statement in which viruses identified only from metagenomic data are considered to be bona fide viruses and thus candidates for taxonomic assignment [ ] . the expanding diversity of the known virosphere also presented challenges. a recent analysis of metagenomes of geographically and ecologically diverse samples led to the discovery of , new partial dsdna viral genomes encoding more than . million proteins, % of which had no sequence similarity to proteins from known virus isolates [ ] . other metagenomic studies have revealed similar diversity in ssdna and rna viruses, particularly in marine ecosystems [ ] . this has led ictv to consider a far broader framework for taxonomic assignment of viruses, recently approving the establishment of a taxonomic hierarchy that includes ranks (realm, subrealm, kingdom, subkingdom, phylum, subphylum, class, subclass, order, suborder, family, subfamily, genus, subgenus, and species), thus expanding the range even beyond those currently available for other organisms [ ] . the sheer volume of new virus genomes identified by metagenomic studies has also led to the development of new bioinformatic tools, that are increasingly being applied for automated virus classification of viruses, based almost exclusively on nucleotide sequence data [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . while the classic tools of virus discovery and characterization (e.g., em, serology, and tissue culture) are still widely used, ngs allowed for the rapid identification of an enormous repertoire of viruses, thus exponentially expanding the boundaries of the known virosphere. the resultant genomic sequences allowed for their accurate taxonomic assignments, analysis of their phylogenetic and evolutionary relationships with other viruses, and evaluation of the potential risks they may present to humans and wild or domestic animal populations. below are a few representative examples of how ngs transformed the known relationships of arboviruses within their respective families. rhabdoviruses contain negative-sense (-) single-stranded rna (ssrna) genomes. they are amongst the most numerous and diverse of rna viruses, naturally infecting mammals, birds, fish, reptiles, and amphibians, as well as insects, arachnids, crustaceans, nematodes, and a wide range of plants [ , ] . most (but not all) rhabdoviruses that infect vertebrates are transmitted by hematophagous arthropods. the rhabdoviridae currently comprises genera containing species and one unassigned species [ ] . of these, viruses assigned to seven of the genera (vesiculovirus, ephemerovirus, tibrovirus, hapavirus, ledantevirus, curiovirus, and sripuvirus) are considered to be arboviruses. viruses assigned to the newly characterized genus almendravirus appear to be insect-specific [ ] . viruses assigned to the genus tupavirus have been isolated only from vertebrates but may possibly have arthropod vectors. complete coding sequences are now available for more than other rhabdoviruses, many of which have been isolated from or detected in arthropods, but they have not yet been formally classified. while the classic tools of viral discovery (e.g., em, serology, and tissue culture) are still widely used, ngs has played a central role in recent genome sequencing efforts, revealing diversity, not only in the ecology of rhabdoviruses but also in the structural diversity of genome architecture [ , [ ] [ ] [ ] [ ] [ ] [ ] . in addition to the five canonical rhabdovirus structural protein genes (n, p, m, g, and l), it is now recognized that rhabdoviruses commonly contain multiple long open reading frames encoding putative accessory proteins, mostly of unknown function. ngs has also facilitated studies of the evolution of rhabdovirus genome organization [ ] and revealed the importance of arthropods in the evolutionary history of rhabdoviruses [ ] . according to the current international committee on taxonomy of viruses (ictv), classification of the order bunyavirales encompasses families of segmented (-) ssrna viruses-arenaviridae, hantaviridae, nairoviridae, peribunyaviridae and cruliviridae, mypoviridae, fimoviridae, wupedeviridae, phasmaviridae, and phenuiviridae-a classification based on structural, genetic, and antigenic characteristics [ ] . bunyavirales is a diverse order with a large number of viruses associated with human, veterinary, and plant disease, as well as being vectored by arthropods (mosquitoes, ticks, sandflies, and thrips) and infecting a wide range of other invertebrates. the recent discovery of gouléako (golv) [ ] and cumuto (cumv) [ ] viruses (the latter with ngs) which are evolutionarily related to but distinct from viruses in the genus phlebovirus, family phenuiviridae, suggesting they are to be assigned to the new genus goukovirus. in the past five years, ngs has revolutionized understanding of the vast diversity of this order, by allowing genetic identification of previously uncharacterized and unassigned bunyaviruses, which in turn provided a complimentary approach to the gold standard of classification (structural, genetic, and antigenic characteristics) for a more refined taxonomic classification. combined, these approaches will be instrumental for enhancing our understanding of their ecologic and geographic distribution, as well as public health impact. the family flaviviridae comprises positive-sense (+) ssrna viruses. the family contains several serious human pathogens, including dengue, yellow fever, zika, japanese encephalitis, west nile, and tick-borne encephalitis viruses (all arboviruses in the genus flavivirus) and the hepatitis c virus (a member of the genus hepacivirus). members of the genus flavivirus, like the alphaviruses (see section . ), are a diverse group of arthropod-borne viruses that are found on every continent except antarctica. several flaviviruses have been discovered and characterized recently, mainly through chance or increased surveillance efforts, and facilitated through ngs. newly characterized viruses include the mercadeo virus (mecdv), from pools of culex species mosquitoes in panama [ ] , sabethes flavivirus (sbfv), from sabethes belisarioi in brazil [ ] , the la tina virus (ltnv), from aedes scapularis in peru [ ] , the long pine key virus (lpkv), from anopheles crucians in the florida everglades, and the kampung karu virus (kpkv), from anopheles tesselatus in borneo [ ] , aedes flavivirus (aefv), from aedes albopictus laboratory colony that originated in thailand [ ] , xishuangbanna flavivirus (xfv), from aedes albopictus in china [ ] , and the cuacua virus (cucuv), from mansonia ssp. in mozambique [ ] . one unexpected finding was the discovery of segmented viruses that grouped in the family flaviviridae and were more closely related to flaviviruses than members of other established genera. the jingmen tick virus (jmtv) is unique in the family flaviviridae with a four segment positive-sense genome [ ] . traditional sanger sequencing generated the ns and ns gene sequences but could not connect these within a single genome segment. phylogenies based on either ns -like or ns -like sequences, which are encoded on two of the four segments, showed jmtv falling basal on the flavivirus tree and clearly distinct from the other viruses in this genus. the remaining two segments did not appear to have a flavivirus origin. jmtv has been isolated from cattle, monkeys, and ticks (rhipicephalus and haemaphysalis spp.) [ ] . this prototype virus has lent its name to the newly identified segmented flaviviruses, and other viruses have recently populated the jingmenvirus clade. similarly, the guaico culex virus (gcxv) consists of five segments, and initial studies suggested gcxv is insect-specific, based on its isolation from culex ssp. mosquitoes [ ] . additional potentially insect-specific four-segmented viruses include shuangao insect virus (saiv ), the wuhan flea virus (whfv), wuhan aphid virus (whav ), wuhan aphid virus (whav ), and the wuhan cricket virus (whcv) [ ] . interestingly, sequences that are similar to toxocara canis, a larva roundworm, and tentatively named t. canis larva agent virus (tclav), are distantly related to jmtv and appear to be the first evidence of a flavivirus-line organism in a member of the phylum nematoda [ ] . the discovery and characterization of a segmented genome flavivirus has significant implications, as it reveals that rna virus segmentation is an evolutionary process that has occurred in previously unanticipated circumstances. the alphaviruses are a diverse group of (+) ssrna arthropod-borne viruses that are found on every continent except antarctica [ ] . there were no known mosquito-only alphaviruses until , when analysis by ngs of a mosquito-pool from the negev desert in israel showed the presence of an alphavirus, the eilat virus (eilv) [ ] . further analysis showed that, although eilv could infect mosquito cells, it was unable to replicate in vertebrate cells [ ] . eilv is considered a vaccine candidate, as it can produce immunity without replication in the vertebrate host, illustrating the importance of such discoveries, which can lead to novel platforms for the prevention and/or treatment of disease [ ] . reoviruses are a diverse family of double-stranded rna (dsrna) viruses that infect a wide range of hosts and have a wide range of characteristics. of the genera, there are only three for which novel viruses have been described using ngs, and the majority of these are in the genus orbivirus. interestingly, because of the structure of the genomes of reoviruses and the conserved sequences at the ' and ' ends of the segments [ ] , it is relatively simple to sequence segments of reoviruses using more traditional techniques. this may be why there are so few novel reoviruses determined by ngs. novel viruses identified using ngs have been assigned to four other genera (seadornavirus, orthoreovirus, dinovernavirus, and cypovirus), all of which are shown in table . refers to year of the publication and not of the isolation of the virus. *not yet formally classified. newly recognized viruses containing a (+) ssrna genome have been proposed to form a new genus negevirus, related to genera of mite-infecting plant viruses (blunervirus, cilevirus, and higrevirus) in the new family kitaviridae [ , ] . originally, six viruses with restricted host range in insects (isvs), designated as negev (negv), ngewotan (nwtv), piura (piuv), loreto (lorv), dezidougou (dezv), and santana (sanv), were identified in and isolated from mosquitoes and phlebotomine sandflies, collected in brazil, the ivory coast, israel, indonesia, peru, and the usa, [ ] . their widespread geographic distribution was documented by several other groups, who reported the isolation and characterization of related viruses in the philippines (tanay virus; tanav) [ ] , trinidad and tobago (wallerfield virus; walv) [ ] , côte d'ivoire (goutanap virus; ganv) [ ] , portugal (ochlerotatus caspius negevirus; ocnv and culex univittatus negevirus; cunv) [ ] , brasil (brajeira and wallerfield viruses), colombia, and nepal. collectively, the close relationship of negeviruses with plant viruses of the genera cilevirus, higrevirus, and blunervirus, coupled with their heterogenous genome organization and architecture, provides support for the possibility that negeviruses are plant-like viruses that could eventually anchor a new virus family [ ] . members of the family mesoniviridae, a newly discovered family of (+) ssrna viruses assigned to the order nidovirales [ , ] , appear to have an extensive geographic distribution but a restricted host range within members of the family culicidae (flies) [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the mesoniviridae comprise of a single genus alphamesonivirus with nine recognized species: alphamesonivirus , including nam dinh (ndiv) [ ] , cavally (cavv) [ ] , ndiv a . [ ] , ndiv ngewotan, and ndiv houston [ ] viruses; alphamesonivirus , including the single isolate of the karang sari (ksav) virus, and the four bontag baru (bbav) isolates sampled in the early s in indonesia, but only recently characterized [ ] ; alphamesonivirus , including the dak nong virus (dknv), the three isolates of kamphaeng phet (kphv), sampled in indonesia and thailand in the mid- s [ , ] ; alphamesonivirus , including the casuarina virus (casv), isolated in australia from coquillettidia xanthogaster mosquitoes [ ] ; alphamesonivirus , the african hana virus (hanav) [ ] ; alphamesonivirus and , including ofaie (ofav) and kadiweu (kadv) viruses, isolated in the pantanal of brasil from mansonia sp. mosquitoes, respectively [ ] ; and alphamesonivirus- and , including the african nse (nsev), and meno (menov) viruses [ ] ; and the distinct yet unassigned species, the yichang virus [ ] , isolated from culex sp. mosquitoes in china. across several generations, virus hunters have left a profound legacy, both to science and to the broader global community. in the field, their work has often been conducted in difficult, demanding, and sometimes dangerous circumstances. in the laboratory, they have developed and applied tools and methodologies that led to improved diagnosis, prevention, and treatment of viral disease, and still lie at the center of virology today. others working at more fundamental scientific levels have used their virus isolates as scientific models, opening the door to a revolution in molecular and cellular biology. yet, their work continues. viral disease emergence remains one of the most serious threats to humanity, with potentially devastating social and economic consequences. recent examples, such as sars, mers, henipa-, ebola, and zika viruses, illustrate the threat that unidentified or poorly characterized viruses can, and almost certainly will, continue to present. equally devastating emerging diseases of livestock, fisheries, and crops threaten food production and livelihoods. as history has repeatedly shown us, technological revolutions have been often accompanied by periods of progressive disinvestment in training for the eclipsed technologies of the past, and in our case, classical virology. the recent emergence of the zika virus in the americas has reinforced the notion that traditional methods of virus discovery and new technologies offer a complimentary toolkit, especially in resource-poor settings that can be seamlessly integrated in the service of public health. it is our hope and expectation that new generations of virus hunters will appreciate the legacy of their predecessors and complement the power of ngs, metagenomics, and bioinformatics, not only to advance viral evolutionary biology, but to understand and limit the potential impacts of emerging viral disease. funding: this work was supported in part by nih grants r ai and u ai . the funding agencies had no involvement in the writing of the report or in 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mosquitoes in vietnam a new species of mesonivirus from the northern territory, australia genome sequences of five arboviruses in field-captured mosquitoes in a unique rural environment of south korea isolation and characterization of a novel mesonivirus from culex mosquitoes in china mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range novel viruses isolated from mosquitoes in pantanal, brazil the authors thank ashley rhame and dora salinas for excellent help in preparation of the manuscript. the authors declare no conflict of interest. key: cord- - bjdppvq authors: escursell, sílvia; llorach, pere; roncero, m. blanca title: sustainability in e-commerce packaging: a review date: - - journal: j clean prod doi: . /j.jclepro. . sha: doc_id: cord_uid: bjdppvq online purchasing, and hence e-commerce packaging production and use, have grown steadily in recent years, and so has their environmental impact as a result. this paper reviews the evolution of packaging over the last century through a compilation of scientific literature on e-commerce packaging focusing on its environmental side. the primary aims were to identify research gaps in e-commerce packaging and to propose new research lines aimed at reducing its environmental impact. a systematic search of abstracts was conducted to identify articles dealing with sustainability in e-commerce packaging in order to better understand changes in materials and formats, identify problems such as oversizing and allow prospective readers to become acquainted with the latest innovations in materials, sustainability and logistics. based on existing research, packaging materials and technology evolved rapidly until the s. later, however, it has become increasingly difficult to further reduce their cost and environmental impact. also, some packaging products continue to be made from non-renewable materials and thus restrict growth of e-commerce. further research is needed with a view to producing new packages from renewable sources such as cellulose-containing materials, which are widely available in nature, or from recycled cellulose-based materials such as cartonboard. improving distribution processes with new, more effective tools could additionally help alleviate the environmental impact of packaging. similarly, new production processes such as additive manufacturing and d printing might help optimize package volume and shape, thereby facilitating more sustainable production through, for example, reduced co( ) emissions. currently available technology can be useful to rethink the whole e-commerce packaging paradigm, which has changed very little over the past few decades. e-commerce continues to grow every year in many developed countries. analysts have recently predicted that its market penetration will have increased by up to % by the year (taylor, ) . this prediction is consistent with the fact that the proportion of online purchases rose from % in , where billion packages were shipped, to % in (eurostat, ; monnot et al., ; zhou, ) . as shown by some consumer studies (pålsson, ; rizet et al., ) , this trend has had an adverse impact on the environment in the form of increased co emissions and energy use. although and increasing number of customers now prefer online buying because it is more convenient, the favourable or adverse effects of e-commerce on the environment remain uncertain. thus, the covid- pandemic has boosted online shopping (kim, ) by, for instance, forcing many physical stores to start selling online -a trend that is unlikely to be reversed in the future. there have been substantial changes in the purchasing behaviour of consumers, many of whom have bought something online for their first time during the pandemic. many are expected to continue shopping online -at least until an effective vaccine for sars-cov- is foundthrough fear of being infected at large malls (organization, ) . research into the environmental impact of e-commerce and traditional in-store shopping have revealed that, for example, brick and mortar retailing (i.e., buying at physical stores) can reduce co emissions by up to % (cairns, ; liyi, ; van loon et al., ; wiese, ) or even % in some cases (carling, ) . based on available data, ecommerce is an effective choice for non-urban delivery over long distances (morganti et al., ; moroz, ; wang and zhou, ) as it avoids using private means of transport to reach urban areas, which is where malls are usually located. the main problem as regards delivery in urban cities arises in the 'last mile', where a number of factors including package type, material and size, and consumer behaviours, are all major contributors to carbon emissions (manerba et al., ; van loon et al., ; visser, ; world economic forum, ) . the fact that packaging materials have a direct impact on energy use -and hence on logistics and waste production-is arousing increasing concern (fichter, ; pålsson, pålsson, , shvarts, ; sivaraman, ; wikstrom, ) . as can be seen from fig. , producing the amount of packaging needed for one person's weekly consumption of food (viz., % of the supply chain energy) requires using a large amount of energy (kooijman, ) . package weight and volume are also important because they influence energy use for transport. fig. . amount of energy needed, in mj, for one person's weekly consumption of food. adapted from (kooijman, ) . overall, existing studies highlight the need to develop packaging solutions based on alternative materials to ensure that energy is efficiently used and waste reduced. overpackaging continues to result in overuse of materials and energy, and thus influences the impact of production and transportation processes (lu et al., ; monnot et al., ) . customer satisfaction is the last link in the e-commerce chain (elgaaied-gambier et al., ; yu, ) . according to garcía et al. ( ) , % of e-customers would shop online again if they were awarded premium packaging. companies should therefore improve consumers' experience through functional, aesthetic presentation of packages, and preservation of their brand image. moreover, they should strive to control the direct and indirect environmental impacts of their packages through green messages. for example, tu et al. ( ) found . % of manufacturers to provide incorrect recycling information and choice ( ) found % of labels to be false or the result of greenwashing practices intended to deceive customers. some authors (breugelmans, ; monnot et al., ) have examined changes in online consumer behaviour and attached less importance to the visual graphics of products. marketing mix strategies (particularly communication and advertising approaches) are gaining increasing ground because dealers are increasingly perceiving the needs to provide adequate, accurate product information and to grant prospective buyers access to previous customers' opinions. a shift in focus from information about physical products to information about online products is clearly in order if designers and manufacturers are to reduce the need for packaging materials. this paper is organized as follows: section describes the methodology used. section deals with the evolution and state of the art in packaging by first examining primary sources of literature on its history and economic changes, and then analysing sustainable packaging and how specific materials and new ways of thinking can advantageously replace current choices. section depicts today's e-commerce scenario and e-commerce packaging alternatives. some points are illustrated with specific cases to help readers understand the advantages and disadvantages of existing approaches. section discusses the most salient representative innovations in e-commerce packaging on a global • from each article read, the most relevant data were extracted, critical assessment and saved in a document for easy identification: title, abstract, date, keywords, relevant data and contribution to the study (quality of results, limitations, methods, interpretations of the results, impact of the conclusions for the study) furthermore, the following questions were used to select the publications: • does the publication discuss the problems, obstacles or challenges of e-commerce and sustainability? • does the publication analyse in detail the evolution of packaging, both in terms of materials and form? • does the publication analyse individuals or companies that contribute new developments in materials or packaging? • does the publication discuss if these developments are really positive contributions to the problems of e-commerce? • does the publication analyse new opportunities in logistics and new materials? additionally, the applied methodologies were analysed. all articles with unreliable data were excluded as unsuitable for quality reasons. the core of this paper comprises the following sections: ( ) evolution and state of the art in packaging; ( ) current scenario and packaging in e-commerce and ( ) new paradigms for sustainable packaging in e-commerce. table summarizes the methodological aspects of the investigation including keywords, periods of time and databases used to acquire the information. the table includes the content analysis procedure followed to extract relevant information of the qualitative type (e.g., quartile ranking of the journals) and quantitative type (basically, the topics dealt with in the articles). late th century to xxi century ( , where e-commerce has gained increasing importance. to to illustrate the latest innovations in logistics and materials. google scholar, elsevier scopus and academic database discoveryupc server. october to october january to may the scarcity of articles on referenced logistics journals prompted a search for papers published in non-indexed journals from june to may . table . methodology: key words, period considered, and academic databases of the three core sections in the manuscript. this section examines changes in packaging since with emphasis on the materials used in recent decades, and on their economic and environmental impact. also, it shows how sustainable packaging has improved, not only as regards aesthetics, in the meantime. in addition, it uses several case studies to assess the strengths and weaknesses of sustainable packaging initiatives following circular economy. the timeline in fig. summarizes the history of packaging since the late th century. design historians have deemed the period from to the beginning of modern packaging. this period brought about new concepts such as mass marketing and mass production, which ran in parallel with the opening of the earliest supermarkets with their associated low prices and high volumes, as well as with the notion of strategic advertising in the same pack (twede, ) . according to some authors (piselli, ; schleger, ) , this revolution changed consumption habits, promoted new ways of mechanizing production, facilitated the spread of supermarkets and even brought economic benefits to packaging manufacturers and consumers. the packaging materials largely used in the period - were paperboard folding carton, tin and glass, mechanization of which allowed vast amounts of packages to be produced (piselli, ; twede, ) . the advantages cartonboard boxes provided to customers gradually increased the market share of many industrial sectors. in fact, according to davis ( ) , patents on up to different types of boxes were filed in this early period. the scarcity of materials during the second world war ( ) ( ) ( ) ( ) ( ) ( ) ( ) led to their preferential use for making war-related products that were sent to soldiers in battle. this left the general population lacking in resources. packages were then largely made from steel (shipping containers), tin (cans), glass (bottles), paper (containers), kraft paper (bags), cloth (bags) or wood (boxes) (risch, ; schleger, ; sheldon, ) . in that time of shortage, people preferred to pay few cents more for products held in high-quality, reusable containers such as glass bottles. the s witnessed a boom in marketing and communication through packaging; however, they also started an age of waste-related problems and shorter product life cycles (so-called 'planned obsolescence'; jorgensen, ) . packaging was then almost more important than the products themselves -so much so that james pilditch called it 'the silent salesman' (cheskin, ; maffei and schifferstein, ; opie, ; pilditch, ; piselli, ; vilnai-yavetz, ) . a new age of self-service in supermarkets then began that allowed consumers to stock up products faster and without waiting to be served (quinn, ) . at that point, it was necessary to understand consumers' needs and to apply marketing mix techniques such as market research, merchandising and advertising to better fulfil them (cheskin, ; kotler, ; quinn, ; silayoi and speece, ; vilnai-yavetz, ) . until the s, packaging materials had remained essentially unchanged because marketing departments and designers had focused on shape, colour and size to ensure optimal viewing of products on the shelves (cheskin, ; silayoi and speece, ; vilnai-yavetz, ) . louis cheskin, an innovative marketing person and psychologist, coined the concept 'sensation transference' and provided experimental evidence for the need to arouse people's emotions through the aesthetics of packaging design. this meant that packages should not focus on aesthetic values such as shape, size, colour or graphics to attract customers' attention, but rather on assigning values of the products to their packages so that customers would be able to discriminate between the two (cheskin, ) . the s and s have been deemed the golden age for advances in technology and space travel. the advances included the production of new materials such as vapourand water-proof plastics, aluminium and adhesives to cater for the needs of the packaging industry. although the earliest plastics (e.g., john wesley hyatt's celluloid) were discovered in the th century, they were not used for packaging until the s and s (wudl, ) because of their high combustibility and short lifetime. at the time, plastic was the main material for all types of packaging because it was easily pliable in different shapes, durable, hygienic, flexible and inexpensive. polyethylene and polyethylene terephthalate (pet) were the most widely used materials in water bottles and plastic bags (opie, ; risch, ) . scientific and technological advances fortunately led to a more humanistic approach. thus, materials can now be scrutinized at deeper levels such as those afforded by nanotechnology. in fact, scientists have shown that some nanoscale materials can adapt themselves to many other materials and enhance their properties to unbelievable levels as a result (doordan, ; leydecker, ; watson, ) . the term 'nanotechnology' was coined by the japanese scientist norio taniguchi at a conference of the japanese precision engineering society in . nanotechnology can be very useful to understand the physical, chemical and biological properties of materials at a very small scale (leydecker, ; martín-gago et al., ) . the concept of sustainability emerged in . for humans to continue to enjoy nature, it was deemed essential to be aware that the amount of fossil resources available for manufacturing materials was limited, and also that greenhouse gas (ghg) emissions from transport and other human activities had adverse effects (doordan, ; jorgensen, ; lyla and seevakan, ; manzini, ; rizet et al., ; shvarts, ; watson, ) . in , pira international devised new rules for packaging in the st century. previously, the eu directive on packaging and packaging waste ( / /eu) (european parliament, ) had taken several steps to control packaging waste and foster the recycling concept (sturges, ) . the goal was to recover - % of all packaging waste and recycle - % of all packaging by . this directive was amended in (european parliament, ) to add 'new recycling and recovery targets to be achieved by : % preparing for re-use and recycling of certain waste materials from households and other origins similar to households, and % preparing for re-use, recycling and other recovery of construction and demolition waste' (european commission, ) . based on a survey conducted by cone communications in , % of consumers were being more environmentally conscious and taking action with better choices when shopping at supermarkets. in fact, many consumers were willing to pay an additional % over the usual price for a sustainable container (hitchin and bittermann, ; kotler, ; lindh, ) . on the other hand, customers buying online were unaware of the need for sustainability; rather, they prioritized other, more appealing variables such as price, volume and time of delivery (monnot et al., ; shvarts, ) . in , the european union revised the legislation again under the concept 'circular economy package' and made new proposals that all member countries of the european commission were to adopt by , namely: at least % of municipal waste and % of packaging waste should be recycled, and municipal landfill volume should be reduced by at least %. the packaging sector clearly needs research and production of emerging materials as alternatives to plastic and fossil-based materials. one form of evidence is the presentation of existing choices such as edible and cellulose-based materials on the market. (janjarasskul and krochta, ) classified edible materials as proteins, polysaccharides, lipids and resins. proteins from wheat, soy, milk and corn are used to improve optical and mechanical properties, while polysaccharides such as cellulose derivatives, starch, chitin, pectin and alginate are meant to improve gas-barrier and mechanical properties. lipid materials such as glycerol, wax and resins added to composite materials act as moistureprotective films (janjarasskul and krochta, ) . for instance, notpla's ooho is a seaweedbased material used as edible bubbles of water intended to replace plastic bottles. kombutcha, which is obtained by fermentation of tea sugars, is one other alternative edible material. because it generates no waste, the biodesign company makegrowlab has deemed it very useful for packaging (shvarts, ) . according to carlin ( ) , sustainability in e-commerce can be accomplished by favouring the use of paper and paperboard materials for packaging. in this line, mirjam de bruijn has developed the unconventional package called 'twenty'. this product reduces the water content of home care, beauty and personal care products by %, thereby allowing smaller cardboard packages to be used. in fact, twenty reduces the use of packaging materials and avoids the need for plastic bottles, which decreases transportation costs (solanki, ) to an extent that may cause a shift in consumers' behaviours. packaging materials should not only be environmentally friendly, but also pose little problem over 'the last mile', which is the greatest hindrance to e-commerce expansion at present. companies are struggling to deliver lighter packages as expeditiously as possible, but obviously at a cost. for example, ikea charge a high price for home delivery of its products, but it is their customers' decision to pay it (yu, ) . on the other hand, to keep their customers satisfied the online supermarket ulabox has not levied last-mile charges even though this obviously detracts from the company's turnover (garcía et al., ) . some studies have examined potential solutions to the last mile problem. such solutions include locker-based automated parcel stations (aps), pick-up points (pp) and parcel machines allocated in various areas for customers to collect their purchases (morganti et al., ; moroz, ) . amazon and google are extensively using the parcel locker solution. for other companies, the click-and-collect concept allows consumers to buy products online and collect them at a physical store (roger and batty, ) . one limitation of this concept is that companies still use the same types of packaging for their e-commerce channels (carrillo, ; ruesch et al., ) . as can be seen from fig. , both shapes and folding in cardboard boxes for transportation have remained almost unchanged. this subject is addressed in greater detail in section . through several case studies which show that the same form and divider concept, and similar materials, continue to be used. (davis, ) . (b) contemporary design (brildor, ) when (papanek, ) wrote design for the real world, he demanded that the role of product designer should be played with a more analytical and self-critical attitude. he insisted that products should be efficient and sustainable rather than merely aesthetically pleasing. in contrast, however, concepts such as 'eco-design', 'green design', 'design for environment' and 'sustainable design' have become the norm even though they do not respond to papanek's ideal and remain more akin to the linear model of the 'take-make-usedispose' process (moreno, ; oxman, ) . the earliest notions leading to the concept of circular economy (ce) arose in the s (stahel, ) and, especially, with pearce and turner in (evans and bocken, ; ghisellini, ; gregorio et al., ) . manzini ( ) focused on the environmental consciousness on the manufacturing process of new j o u r n a l p r e -p r o o f products such as packages, and also to consumers' attitudes in the s and s. the emerging political, economic and design awareness led to the development of new products that were intended to be more ethical and positive towards the environment. circular economy (ce) is a business model based on a closed-loop system that uses biological and technical inputs separately (bocken, ; ghisellini, ; macarthur et al., a macarthur et al., , . ce adds value to existing materials and avoids overexploiting natural resources, which helps to reduce waste. the 'butterfly diagram' developed by the ellen macarthur foundation (macarthur et al., b) encourages companies to rethink their manufacturing processes by following ce methodology. a sizeable number of studies on ce for packaging have addressed the role played by business models and stakeholders, existing packaging strategies for materials, logistics, and legislation and policies, among others (gregorio et al., ; meherishi et al., ; moreno, ) . the delft university of technology, where the r strategy was developed (klooster, ) , has conducted extensive research into ce as applied to packaging. table summarizes the r approach, the four rs standing for 'recycle', 'reuse', 'renew' and 'rethink'. in this context, recycling is using materials from packaging waste to produce new materials for making new packages; reusing is harvesting, washing and using packaging products once more; renewing is using biodegradable, compostable or renewable materials for packaging; and rethinking is finding new design methods to improve existing packaging solutions socially and environmentally. the current trend is to recycle and to search for biodegradable, compostable or renewable packaging materials that can be easily disposed of with no waste. rethinking packaging design is being considered to depart from conventional uses. at present, global e-commerce is being led by amazon, ebay and alibaba/aliexpress (fernández, ) . amazon dispatches more than billion packages each year (an estimated packages each day) and have recognized that their carbon footprint in was . million tons (amazon, ; shieber, ) . covid- increased the number of virtual visits to amazon in march to . billion visitors (baltrusaitis, ) . this is a huge amount of material and a massive wastage of energy. for this reason, amazon is considering reducing secondary packaging in all deliveries in the future; however, they will have to rely on manufacturers to achieve this ambitious goal, and not all are willing to spend money and time in innovating and redesigning secondary packaging. this section examines various strategies companies are currently using to reduce co emissions and energy wastage in e-commerce packaging. amazon is currently working on the concept of 'material reduction' with their ffp programme. the secondary packaging they use must protect the product, minimize the amount of material used in each pack and maximize its recyclability in order to reduce waste production (amazon, ). amazon's certification requirements include using rigid hexahedral boxes of the following minimum dimensions: . mm (length) × . mm (width) × . mm (height). amazon makes its boxes with corrugated cardboard and other cellulosic materials -or plastics such as pet, hpde and pp. all must be % recyclable and airtight sealed with a long enough piece of masking tape so that no material will be wasted during shipment. amazon even recommends using technology for measurements. also, packages must be labelled with appropriate information, the volume of each product should not exceed the holding capacity of its container and packages must be easy to open by customers. packages should be made from as little material as possible. 'dematerialization' is a widespread approach to reducing material and energy use, production of solid waste and co emissions. victor papanek illustrated the concept briefly back in in describing a particular anecdote in his book design for a real world (papanek, ) . there, he proposed making toilet paper an inch less wide to reduce the wastage of millions of litres of water each day. based on circular economy principles, the manufacturer of the saica pack (saica, ) uses waste as a secondary raw material to produce eight different cardboard boxes (seven for small items and one big box for shipping deliveries) for amazon spain under the ffp program. although amazon's warehouses can recycle % of their own material and return it to saica, they cannot control the fate of everything they deliver. mondi group ( ) produces recycled paper and sustainable flexible plastic for packaging. as material manufacturers, they are continuously working jointly with recycling companies and sustainable material suppliers to broaden their range of solutions. although they have competitive prizes, they only manufacture packages in standard sizes. pro carton is a cartonboard manufacturer that has grown . % each year over the last decade as a supplier of a sustainable alternative to plastics. cellulose in their cartonboard comes from sustainable forests (fsc) and is mixed with recycled material. one should be aware, however, that some recycled materials such as cardboard do not have the same properties as the pure materials. this is so because recycled materials have shorter fibres and these are less resistant to handling than are long fibres. the greatest advantage of recycled fibres is that they save trees from felling in addition to % of water and % of electricity per ton of paper (piselli, ) . one problem with online purchases is that most products are packaged in the same type of material: corrugated paper (carlin, ; pålsson, ) . by contrast, food ecommerce has introduced more complex variables into packaging that require new, effective developments. packaging regulations have established three different layers of packaging. the person who unwraps a package at any level is deemed the end user of the material. it is therefore important to understand which level of packaging a company is bracketed at in order to determine its total obligation tonnage and total cost. there are three main tiers here, namely: • primary packaging, which encompasses the wrapping or containers handled by the consumer or end user and serves to protect and advertise the product (e.g., foil wrapped around a chocolate bar). • secondary packaging, usually in the form of large cases or boxes that are used to group quantities of primary packaged goods for distribution and for display in shops (e.g., cardboard boxes containing large numbers of foil-wrapped chocolate bars). • tertiary packaging, which comprises the containers used to gather packaging groups into larger loads for transport in order to facilitate loading and unloading of goods (e.g., wooden pallets and plastic wrapping). online grocery retailers typically use corrugated board packages and paper or plastic bags (mostly biodegradable plastics). why are they still using those materials if new alternatives are needed in e-commerce? in fact, a clear demand for new materials exists in this area. standard stores are increasingly using paper bags instead of corrugated board packages for home delivery (carlin, ; pålsson, ) , thereby saving % on energy. the question thus arises as to how e-commerce materials for reducing this impact can be obtained. although e-commerce can reduce co emissions in non-urban areas -and also in urban sectors under aps or pp-, the impact of packaging materials and energy requirements should be the main consideration here. this section is concerned with existing alternatives to standard packaging designs. very little attention has to date been paid to the original flat wine bottle redesigned by garçons wines (garçons wines, ), shown in fig. , which can be delivered in a letterbox. the bottle is manufactured from % recycled pet, so it will not break in freight deliveries; also, it is % recyclable after use. at only g, it is % lighter than a standard glass bottle, so the environmental impact of its transportation is much smaller. however, this new form of packaging can alter consumers' perception and lead them into believing that the wine it contains is of lesser quality. the winepack (total safe pack, ) was developed jointly by itene and cartonajes font to protect wine bottles. this packaging system (fig. ) has a special folding that reduces bottle breakage by %. the outer box consists of a double layer of mm thick corrugated cardboard and the inner piece of a single layer of mm thick corrugated cardboard. the package has a double thickness flange at the top and bottom. the winepack uses a fair amount of material and is thus expensive for e-commerce. because it is single-use, it increases environmental impact and material wastage -consumers tend to have a negative perception when they receive an overpacked product they have purchased online. in fact, according to monnot et al. ( ) , saturation with materials generated once a package is disassembled can be the source of bad experiences for consumers. in any case, the winepack provides improved protection for bottles and reduces product losses as a result. fig. compares a standard package for wine transport with the winepack, which is a corrugated cardboard box with dividers (olivares, ) , in terms of bottle safety, and table shows the final additional cost of packaging bottles. as can be seen, the winepack provides substantial savings in bottle handling. thus, it avoids bottle breakage, which reduces losses and their associated costs; also, it affords transportation of bottles in greater numbers without breaking. as a result, the winepack is a cost-saving, environmentally friendly solution. cost savings do not offset packaging price relative to standard packaging, however. moreover, the actual benefits of using the winepack over a conventional wine package are still to be demonstrated. for example, the winepack uses times more corrugated cardboard, which means increased transport costs and co emissions. one should bear in mind that the environmental tax for cardboard is . €/kg (ecoembes, although not intended for e-commerce food purchases, the scudopack is another choice for diminishing the environmental impact of packaging and reducing the amount of material used. as shown in fig. , scudo systems are typically used to protect furniture, windows, marble and doors, and recommended for all types of electronic products including radiators and photovoltaic panels, because they are easy to apply and highly resistant to impacts. thus, they have been found to decrease breakage by up to % and to reduce packaging volume -and transport costs as a result. their advantages over conventional packages include a substantial reduction in material volume, costs and product breakage -a scudopack can withstand consecutive impacts without damage, so it fulfils ista regulations. metsä board ( ) recently detected a high consumption of bubble wrap and minipolystyrene foams (so-called 'packing peanuts') to secure products in e-commerce packaging. although conventional expanded polystyrene (eps) packing peanuts are light and durable, they are not degradable, so they can be the source of health problems for production workers. alternative biodegradable starch-based peanuts are more expensive than are eps packing peanuts (cheng kwee et al., ) . iiro numminen found cutting a pattern in cardboard packaging to provide a secure package with the same amount of material and less cost (see fig. ). this idea won him metsä board's 'better with less' prize, which is awarded to innovative packaging solutions (metsä board, ). in finland, repack offers a bag for reusable packaging that reduces co emissions by up to %. instead of bio-based material, which is not reusable, repack is made of polypropylene (pp). this polymer is long-lasting, recyclable and lightweight, and has a reasonable impact on cost saving. in any case, the manufacturer is open to using other biomaterials that might be found on the market. repack's proposal is that customers themselves should return their empty bags through a post office (see fig. ). the service, however, is unsuitable for fragile contents such as liquid foods. compares the previous alternative packaging solutions in terms of cost savings, material volume and function. as can be seen, the scudopack is the most costeffective solution, as well as the most functional and best performing, and the one using the least material. on the other hand, the winepack and garçons wines solutions are effective in terms of material volume and functionality, but not in cost, which is high relative to the scudopack. finally, repack and the stretching inner part fall in between the previous two j o u r n a l p r e -p r o o f extremes, with acceptable cost savings, and good material volume and functionality properties. fig. . comparison of the five solutions examined in terms of cost saving, material volume and function on a scale from to . fig. compares the previous solutions in terms of reusability, returnability, recyclability and adaptability to product volume. as can be seen, the garçons wines and repack solutions are the indisputable winners in these respects. repack is reusable, made from recyclable material and returnable, but cannot easily adapt to any type of product because it is only available in a standard shape. garçons wines have focused on adapting their solution to particular products and even specific circumstances of the sector (ecommerce in this case), whereas the winepack, scudopack and stretching inner part have been conceived for product adaptability and recyclability. fig. . comparison of the five solutions examined in terms of the indicators reusable, returnable, recyclable, and adapted to product shape and volume. in summary, the garçons wines and repack solutions are the best choices for ecommerce but are made from non-biodegradable materials obtained from non-renewable sources. the other three solutions are made from cardboard, which is biodegradable and comes from a renewable source (cellulose fibre). this topic is dealt with in greater detail in section . . today, the world is at a very special time in history. in fact, the early st century is witnessing substantial changes through the fourth industrial revolution, also known as 'the digital revolution'. the changes include the development of exponential technologies such as artificial intelligence (ai), autonomous vehicles, d printers, drones, virtual reality, brain-computer interfaces and genetic engineering. d printers, for example, are allowing new materials to be applied with better resolution and in less time. this has enabled dyi printing of products at home instead of buying them (salim et al., ) . in japan, technologies such as internet of things (iot) connectivity, d vision sensors and robots are allowing workers to improve package manufacturing processes (carlin, ) . this is the right time to stop thinking in a linear manner, and to switch to exponential and circular thinking as new paradigms for the human being. the following sections discuss various technological improvements and material enhancements that are expected to lead to a renewed society. by using cost-effective algorithms, us carriers such as ups can save million miles of driving each year (salim et al., ) , thereby considerably reducing co emissions -each day, the company delivers around million shipments. the traditional concept of transportation is being challenged by the advent of autonomous cars and the new information paradigm. autonomous cars avoid having drivers -and the aggressive behaviours of some-on the roads; also, they help reduce fuel consumption. recent studies on transportation strategies for reducing greenhouse gas (ghg) emissions have shown that using appropriate sensors and algorithms can reduce logistic activity and increase the efficiency of autonomous cars. in any case, the fuel market for cars should provide more options such as electricity, hydrogen or biofuels and electrofuels for hybrid cars in order to further reduce carbon dioxide emissions. as suggested by their high environmental impact and the apparent lack of viable alternatives, a thorough life cycle assessment (lca) of electric car batteries is also in order (belvedere, ) . using robots and small drones to deliver packages can reduce emissions on the 'last mile'. this would imply rethinking package shapes and making use of new, light, sustainable materials. to solve this problem, the company matternet (matternet, ) uses a combination of vans and drones to make shipments more efficient in accordance with the size of the package to be delivered, thereby reducing ghg emissions (condliffe, ) . the company itself is revolutionizing transport standards and considering introducing drones as an effective delivery option for developing countries in africa. they intend to use technology to make the leap to new ways of transport in much the same way as the mobile phone improved communication (salim et al., ) . amazon gave the option to send shipments with drones in under the 'prime air' concept (amazon, ) ; the project, however, was abandoned because it was not as effective as predicted (vincent and gartenberg, ) . ups went further in this direction thanks to its being authorized by the federal aviation administration (faa) to use drones for hospital deliveries (ray, ) . this was made possible by the digital and technological revolution leading to increasingly powerful devices at increasingly low prices (ray, ) ; for the moment, however, the system can only be used by commercial airlines and is subject to stringent regulations. in any case, adopting drones should be the concern of citizens, governments and air forces as it might lead to collapsed skies unless their use is strictly regulated. for this reason, alternative technologies are currently being sought one of which involves using pneumatic tube systems invented in the late th century (woodford, ) . such systems are still used by banks, hospitals, supermarkets and logistics centres, among others, in the united states. elon musk's hyperloop relies on this concept, and the situation is highly likely to improve in the long term and allow new methods of fast, efficient transport to be developed (dudnikov, ) . in any case, progress towards reducing the impact of the last mile could be furthered by a change in consumers' attitude. for instance, if most customers collected their orders at specific places, a number of transport problems could be solved and packaging wastage reduced. as stated above, amazon is already installing automated parcel machines and establishing pick-up points for personal collection in urban areas. in fact, they have established several supermarkets in the usa where artificial intelligence is used to avoid the need for staff and to allow customers to purchase their products easily and conveniently (favors, ) . as shown by existing literature, cellulose-based materials have a very low environmental impact relative to other choices (suhas et al., ) . cellulose is one of the most naturally abundant materials (abitbol et al., ; bharimalla, ; klemm, ; li, ; nechyporchuk et al., ; osong et al., ; perepelkin, ; rajinipriya, ; tayeb, ; vilarinho et al., ; yang et al., ) and one of the most important renewable materials (brinchi et al., ; cusola, ; hischier et al., ; osong et al., ; piselli, ) . cellulose can be found in woody and non-woody plants (grass, algae), and bacteria, as well as in waste from forestry and timber industries, agricultural practices and industries, and even from pulp and paper industries (li, ; rajinipriya, ; ramesh, ) . plant cells are the main raw material for paper and cardboard production. the interesting properties of cellulose as a macro structure could be explored for use in disposable packages, but has some limitations as regards barrier properties. by virtue of its exceptional mechanical, physical, thermal, optical and even barrier properties, nanocellulose (nc) appears to have a high potential for a wide variety of uses. recent studies suggest that the food packaging industry is searching for efficient ways to produce this strong, lightweight bio-based material. because it has antimicrobial properties, and is transparent and water-and oxygen-permeable, nc is highly suitable for packaging to be in contact with food (itzela et al., ; li, ; nechyporchuk et al., ; osong et al., ; rajinipriya, ; vilarinho et al., ) . a young generation of design students at aalto university in finland has worked collaboratively with chemists to explore biomaterials from cellulose and develop new approaches for the future. there are some indications that the properties of nc can be further improved. thus, although the crystal structure of cellulose confers it strength, three students (arto salminen, steven spoljaric and jukka seppäla) have found a way to enhance it before spinning (fig. ) in order to increase its water stability and expand its range of uses (kääriaäinen et al., ) . another student (martha yessen) has developed an interesting reaction for converting dissolved cellulose acetate into solid cellulose (lindberg et al., ) . the high versatility of cellulose has enabled the production of new biodegradable materials through a combination of chemistry and technology that expands the scope of cardboard and paper in e-commerce packaging. fig. . cellulose-based filaments from hydrogel suspensions (kääriaäinen et al., ) . iso - : (iso, defines the principles behind material extrusion for additive manufacturing. however, d printing in one of its seven forms can be used to produce packages by material extrusion, vat photopolymerization, powder bed fusion, material and binder jetting, sheet lamination and directed energy deposition. these processes can be applied to various materials but are especially suitable for plastics, bioplastics, other polymers, metals, ceramics, glass or even edible viscoelastic ink for food (braslavsky et al., ; jordan, ; keating, ) . the finnish initiative known as 'design driven value chains in the world of cellulose' (dwoc) uses direct ink writing (diw) and fused deposition modelling (fdm) to print solid and liquid cellulose-based materials (kääriaäinen et al., ; kataja and kääriäinen, ) . in the netherlands, d printing has allowed the industrial designer beer holthuis to print objects with recycled paper in order to reuse material that would otherwise have been wasted. according to holthuis (holthuis, ), each person generates about kg of paper waste each year. d printing enables customized, more sustainable package production and facilitates circular economy. its actual potential, however, should be assessed by comparing life cycles with those of existing conventional choices. tomorrow machine is a swedish packaging studio, product and food concept that has worked on a series of proposals with innventia, a research company, for ekoportal . ekoportal is a futuristic project of the swedish forest industries federation seeking new outputs for cellulose in the near future. one of the proposals, presented in , was a plastic made with cellulose and printed with d technology. this solution has gained ground as a tool for producing flexible objects that can even self-manufacture and self-destruct (billqvist and glansén, ; innventia, ; the swedish forest industries federation, ) . neri oxman, the renowned architect and founder of the mediated matter group at the massachusetts institute of technology (mit), has been searching for several years new biopolymers from renewable sources and considering their return to nature as waste (pangburn, ) . this is what oxman calls 'material ecology'. new ways of manufacturing biopolymers have also been devised. the concept of 'designing for decay', inspired by nature, has been used to obtain organic materials such as cellulose, chitosan and pectinthe most abundant natural polymer-and transform them into objects that will break down over time (lipps et al., ) . once the materials have been obtained, they are used to feed a d printer operated by a water-based robot for additive manufacturing of extruded hydrogel composites (mogas-soldevila et al., ) . according to oxman, the industrial revolution abandoned nature and led to mass production, repetition and practical design, but handicapped imagination (latza et al., ; lipps et al., ) ; however, emerging technologies and new materials are opening up new horizons for creativity. the packaging industry has scarcely changed the structure of folding boxes since the th century even though the recent growth of e-commerce has considerably increased packaging usage and raised the need for effective solutions to the ensuing environmental problems. this paper reviews the state of art of packaging in e-commerce with the aim of depicting the current scenario, identifying gaps in past research and proposing new lines to revitalize the evolution of packaging, which has been stuck since the s. the current scenario for the packaging sector can be easily understood if one considers the following facts: • packaging evolved substantially by effect of the production of new materials until the s. at present, however, it has reached a standstill owing to the need for effective ways of reducing costs and environmental impacts. unlocking this situation will call for new design paradigms to be built. • overpackaging is increasingly common and should be among the concerns of policy makers. • although packaging made from non-renewable materials such as plastics continues to be widely used on the grounds of its recyclability, too strong a dependence on these sources should be avoided at any rate. • package distribution remains one of the main contributors to the environmental impact of packaging and is hence in need of more effective solutions. based on the foregoing, work aimed at reducing the environmental impact of packaging should somehow be guided by the following considerations: • the abundant waste generated by e-commerce -usually in the form of cardboardcan end up being degraded and returned to nature. also, such a widely abundant natural biopolymer as cellulose can be obtained from renewable sources and biodegraded or upcycled after use. • effective guidelines and policies to avoid overpackaging are very much needed. • circular packaging should be promoted by developing sound specific design guides. • production with new technologies such as additive manufacturing and d printing should be further explored to devise new packaging solutions (e.g., packages more closely fitting the shape and volume of the products they are to hold and made from lesser amounts of material). high-performance d printers afford cleaner manufacturing and can alleviate co emissions. the new production technologies are being increasingly used at the industrial scale on account of their low production costs and high throughput. • new logistic strategies such as those based on drones, electric cars or pick-up points should be evaluated in order to identify the best performers as regards environmental impact reduction and ways of using them in different scenarios should be found. • life cycle assessment (lca) studies should be fostered to ensure that the previous research lines will improve on previous choices (e.g., to confirm that a new solution reduces carbon footprint relative to the existing packaging product it is intended to replace). package design should also be subjected to lca in order to ensure that the ensuing solutions are more environmentally friendly than the original ones. nanocellulose, a tiny fiber with huge applications gourds [www document amazon frustration-free packaging program certification guidelines. amazon, . first prime air deliver apeel sciences 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based material reuse rethinking packaging towards a circular economy : accelerating the scale-up across global supply chains towards a circular economy : opportunities for the consumer goods sector towards a circular economy : economic and business rationale for an accelerated transition perspectives on food packaging design attended home delivery: reducing last-mile environmental impact by changing customer habits el nanomundo en tus manos : las claves de la nanociencia y la nanotecnología vans and drones [www document sustainable packaging for supply chain management in the circular economy: a review metsä board [www document water-based robotic fabrication: large-scale additive manufacturing of functionally graded hydrogel composites via multichamber extrusion. d print mondi group url www.mondigroup.com (accessed . . ) thinking outside the packaging box": should brands consider store shelf context when eliminating overpackaging? ari jónsson uses algae to create biodegradable water bottles a conceptual framework for circular design final deliveries for online shopping: the deployment of pickup point networks in urban and suburban areas the last mile issue and urban logistics: choosing parcel machines in the context of the ecological attitudes of the y generation consumers purchasing online production of cellulose nanofibrils: a review of recent advances context perspective on university-industry collaboration processes: a systematic review of literature david gorgues, fundador de totalsafepack [www document packaging source book. a visual guide to a century of packaging design e-commerce, trade and the covid- pandemic processing of wood-based microfibrillated cellulose and nanofibrillated cellulose, and applications relating to papermaking: a review design at the intersection of technology and biology energy consumption in e-commerce versus conventional trade channels -insights into packaging, the last mile, unsold products and product returns selection of packaging systems in supply chains from a sustainability perspective: the case of volvo decay by design: these d-printed organic plastics naturally decompose design for the real world renewable plant resources and processed products in chemical fibre production el vendedor silencioso. cómo realizar envases que venden designing sustainable scenarios: natural-based coatings as a barrier to oil and grease in food paper packaging crowning the customer. how to become customer driven importance of agricultural and industrial waste in the field of nanocellulose and recent industrial developments of wood based nanocellulose: a review plant fibre based bio-composites: sustainable and renewable green materials feel the peel [www document meal kits have a packaging problem revolv [www document ghg emissions of supply chains from different retail systems in europe the future of e-commerce in fmcg freight transport with vans: developments and measures package and print. the development of container and label design alec davis containers go to war amazon's "climate pledge" commits to net zero carbon emissions by and % renewables by [www document eco-friendly packaging materials of the future: brands must focus on infusing new, sustainable packaging materials in order to stay relevant. brand packag. , comparative energy, environmental, and economic analysis of traditional and ecommerce dvd rental networks policy for material efficiency -sustainable taxation as a departure from the throwaway society environmental legislation for packaging in the next millennium -comment cellulose: a review as natural, modified and activated carbon adsorbent cellulose nanomaterials-binding properties and applications: a review the retail apocalypse is far from over as analysts predict , more store closures [www document the swedish forest industries federation total safe pack towards a methodology for developing evidence-informed management knowledge by means of systematic review an investigation of the effects of infographics and green messages on the environmental attitudes of taiwanese online shoppers. sustainability the birth of modern packaging: cartons, cans and bottles diana twede a comparative analysis of carbon emissions from online retailing of fast moving consumer goods nanocellulose in green food packaging cutting through the clutter: purchase intentions as a function of packaging instrumentality, aesthetics, and symbolism here's amazon's new transforming prime air delivery drone home delivery and the impacts on urban freight transport: a review reconstructing the giant: on the importance of rigour in documenting the literature search process deliveries to residential units: a rising form of freight transportation in the u a terrible beauty. a history of the people and ideas that shaped the modern mind transport-related co effects of online and brick-and-mortar shopping: a comparison and sensitivity analysis of clothing retailing potential environmental gains from reducing food losses through development of new packaging -a life-cycle model puma and mit design lab envision a future of self-adapting, performanceenhancing sportswear pneumatic tube transport [www document shaping the future of retail for consumer industries the bright future of fabulous materials based on carbon nanobiopolymers fabrication and their life cycle assessments e-commerce logistics in supply chain management: practice perspective location-routing problem with simultaneous home delivery and customer's pickup for city distribution of online shopping purchases the authors would like to acknowledge funding by spain's ministry of economy and competitiveness: filmbiocel project (ctq - -r, funding also from feder) and microbiocel project (ctq - -c - -r). they are also grateful to the members of the consolidated research group agaur sgr . finally, they thank dr. nicolas maffei, of the norwich university of arts, for sharing his knowledge of packaging history and amy straker for her hospitality. key: cord- -lvcp imi authors: fenichel, eli p; berry, kevin; bayham, jude; gonsalves, gregg title: a cell phone data driven time use analysis of the covid- epidemic date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: lvcp imi transmission of the sar-cov- virus that causes covid- is largely driven by human behavior and person-to-person contact. by staying home, people reduce the probability of contacting an infectious individual, becoming infected, and passing on the virus. one of the most promising sources of data on time use is smartphone location data. we develop a time use driven proportional mixing seir model that naturally incorporates time spent at home measured using smartphone location data and allows people of different health statuses to behave differently. we simulate epidemics in almost every county in the united states. the model suggests that americans' behavioral shifts have reduced cases in %- % of counties and for %- % of the population, depending on modeling assumptions. resuming pre-epidemic behavior would lead to a rapid rise in cases in most counties. spatial patterns of bending and flattening the curve are robust to modeling assumptions. depending on epidemic history, county demographics, and behavior within a county, returning those with acquired immunity (assuming it exists) to regular schedules generally helps reduce cumulative covid- cases. the model robustly identifies which counties would experience the greatest share of case reduction relative to continued distancing behavior. the model occasionally mischaracterizes epidemic patterns in counties tightly connected to larger counties that are experiencing large epidemics. understanding these patterns is critical for prioritizing testing resources and back-to-work planning for the united states. physical (social) distancing in the form of "staying home" is a critical tool to prevent covid- mortality, and will remain so until pharmaceutical therapies or vaccines are widely available. the modeling consensus is that some version of distancing will need to persist for months, not weeks (anderson et al., ; ferguson et al., ) . however, strong distancing can ultimately give way to isolating infectious individuals and targeted distancing measures with sufficient contact tracing capacity (kissler et al., ) . a new tool in the epidemiological modeling of distancing is time use data from smartphone devices. time use provides a measuring contact risk with a recognizable unit that has metric properties unlike arbitrary distancing indexes. here we build on prior epidemiological time use modeling (bayham and fenichel, ; bayham et al., ; berry et al., ) to adapt the common seir framework to a dynamic time use structure that enables differential behavior by health status in order to incorporate smartphone tracking data into a model of the covid- epidemic for every county in the united states. we use these results to characterize the variation in the epidemic and suggest prioritization for testing and targeting for a "back to work" strategy across the united states. the standard seir compartmental epidemiological model does not have a structure for incorporating dynamic behavior that responds to the state of the epidemic (fenichel et al., ) . however, behavior is changing rapidly, and there appear to be strong feedbacks between the covid- epidemic and people's behavior (malik et al., ; villas-boas et al., ) . in prior research, we developed an economic-epidemiological model based on a time-varying conditional proportional mixing structure (fenichel, ; fenichel et al., ) that enables physical distancing behavior to vary based on health state and respond to the state of the epidemic. this structure can readily be adapted to time use with heterogeneous mixing models using empirical time allocation-based contact structures that can be updated within a simulation (bayham et al., ) . these structures can be calibrated using time allocation of americans as measured by their smartphones' locations. the model, which treats all counties independently, suggests substantial heterogeneity in the covid- epidemic across the united states. the model suggests that some counties are likely still experiencing near exponential growth while in other counties cases have likely peaked. in some cases the peak is due to the county's demographic structure. in others it is due to behavior. in case where the peak is causes by behavioral change, reverting to pre-epidemic behavior will lead to a rapid rise in cases -the case in most urban and suburban counties. we find the cell phone data likely provides unreliable measures in many rural counties. we also find that behavior is unable to explain the epidemic in some counties, however these counties appear to be near highly populated counties with large numbers of cases, suggesting substantial county to county spillover. this suggest county-by-county modeling is likely insufficient for some locations. finally, isolating infectious individuals is of first order importance. however, allowing recovered individuals, who are assumed immune in the model, to return to a baseline schedules has modest effects on the epidemiological dynamics in most counties, but a strong case reduction effect in a few places. this has implications for how scarce pcr and serological tests are deployed to help plan for reopening the united states. analysis is the number of the cases the index case would cause in a naïve population. it is measured at the moment an epidemic starts and is a function of behavior. so, varies as baseline time use varies. after fixing , the biological transmissibility parameter (see methods), we plot the variation in the that would occur as a function of time allocated to public prior to the epidemic (mean time from january through february ) (fig ) . this illustrates the importance of the behavior in estimates. the two counties with the lowest are suburban, forsyth county, georgia ( . ) and rockwall county, texas ( . ), followed by the rural arthur county, nebraska ( . ). however, the right tail is inflated by rural counties where people may be spending more time alone (e.g., driving), but away from their homes and that have low device counts (see methods) and likely poor cell phone coverage. historical driving time patterns are not useful to check this assumption because of congestion in urban areas during non-epidemic times. the right tail is dominated by counties like loving county, texas, lake and peninsula borough, alaska, and north slope borough alaska. many of these places are not reporting cases. the distribution in figure , which has a mean . and median . aligns with other estimates of for the united states, e.g., a national mean of . , which was calculated early in the epidemic after some behavioral adjustment (gunzler and sehgal, ) . the match is especially good considering that the right tail in figure is likely inflated. the results seem most credible for suburban, followed by urban counties. outside of rural counties, generally increases with density and urbanization. the local can be quite variable. for example, the five boroughs of new york city are new york county (manhattan) . , bronx county . , kings county (brooklyn) . , queens county . , and richmond county (staten island) . . our results for rural counties based on cell phone data should be viewed with a high level of caution as being out of the house might not equate to mixing and transmission. cell phone tracking data is likely less useful for understanding the epidemic in very low population density counties, at least without a substantial recalibration because how time spent out of the house translates into transmission contacts is likely substantially different. many, but not all, counties are "bending the curve", as defined by having few cases over the last five days conditional on revealed behavior relative a simulation based on average baseline behavior, see methods (fig , fig ) . however, there are some counties where cell phone data suggests that behavior has hardly changed, e.g., new york county, new york (fig panel a) and rockwall, texas (fig , panel e) . indeed, rockwall, texas suggests that the baseline behavior may be too conservative if the correct counterfactual scenario is that people would have increased time outside the home because of seasonal changes. other counties are bending the curve enough to have experienced a peak in cases conditional on current behavior e.g., queens county new york (figure panel b) and forsyth county, georgia (figure panel f). these counties have "flattened the curve," as measured by declining active infectious individuals over the last five days. some counties can have flattened curves or are past the epidemiological peak, but without behavioral change that flattened the curve, e.g., custer county, nebraska and union county, new mexico (fig ) . we note, however, many of these counties have not actually experience epidemics, and the results stem from assuming an epidemic starts in every county once covid- is reported in the state (see sensitivity analysis). there is a third category of county, where behavior is reducing the growth of infectious individuals, but infections are still growing, e.g., new haven county, connecticut ( these counties have "bent the curve," but not flattened it. in all counties it is too early to resume "business as usual." even the counties with low values, e.g., forsyth county, georgia need to maintain distancing for at least a month ( figure , panel f). moreover, forsyth county, georgia illustrates the danger of stopping distancing too early (yellow curve). an important caveat is that the model does not account for interconnections among counties. therefore, while queens county and forsyth county are on a trajectory for a near end of the epidemic, if behavior reverts to baseline and new infectious individuals are introduced into the county, then the epidemic will start again. this is why our model suggests some tightly connected counties, e.g., queens county, are on a better trajectory than experience suggests. overall there are , counties ( . %) accounting for . % of the us population that have bent the curve (fig ) . there are counties ( . %) accounting for . % of the us population that appear over the epidemiological hump. there are counties ( . %) accounting for . % of the us population where behavior has flattened the curve. there are , counties where behavior has not shifted and may have exacerbated the epidemic. for the remaining of counties the differential equation solver does not converge because of changes in behavior and small population sizes. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . the effect of immunity and testing priorities testing is critical. there are two kinds of tests, pcr tests that can detect infectious individuals early for isolation and serological tests that determine who has antibodies. a subset of the serological tests coming online is aims to determine who likely has immunity. we focus on this later type of serological test. our model helps identify where which kind of test should be prioritized. pcr tests are a priority in areas where the curve has not bent or has not bent substantially, e.g., bannock county, idaho and new york county, new york. in these places, it is critical to begin identifying and isolating infectious individuals in order to more rapidly bring the covid- epidemic under control. it is likely also important to maintain pcr testing in counties where the curve has not flattened. serological tests capable of identifying recovered and immune individuals (which are not yet available) are important, and the greatest benefits are in counties where getting recovered individuals back to baseline schedules reduces the greatest share of cases ( figure ) coupled with those counties likely to experience the greatest hardships from infection (maher et al., ) . our analysis suggests where the greatest percent and share of cases are avoided is correlated. the reason is that these counties are most likely to be bending, but not flattening the curve, and where there is a substantial number of recovered individuals that can make a difference, e.g., williamson county, texas ( figure , panel d). the model also shows that allowing susceptible and recovered individuals to baseline behavior (cyan curves in figure ) can lead to slightly more cases than maintaining recent behavioral shifts (green curves in figure ), in some cases, e.g., williamson county, texas. however, it leads to substantially few cases than returning the entire population to baseline (yellow curves in figure ). this suggests relatively low risk of a track, trace, and isolate program. we test the sensitivity of the results to the infection recovery rate and the simulation start date. we reduce the recovery rate from . to days. this reduces the national average to . and median to . but does not change the shape of the distribution. this parameterization produces far fewer cases than observed in most counties. the patterns across the united states remains similar (fig ) to our primary calibration. however, more counties are near the peak of the epidemic, and therefore there is greater value in returning those with acquired immunity to baseline schedules. we find that counties ( . %) are bending their curves accounting for . % of the population. counties have flattened curves ( . % of counties and . % of the population) with counties behaviorally flattening the curve ( . % of counties and . % of population). second, we start every county's epidemic days before the first report in each county. for counties not reporting epidemics we use the date that the last county in the state first reported a first case. this leads to many counties where the epidemic does not happen because of changes in behavior that appear to respond to state wide or national case data. we find that counties ( . %) are bending their curves accounting for . % of the population. counties have flattened curves ( . % of counties and . % of the population) with counties behaviorally flattening the curve ( . % of counties and . % of population). this illustrates the simulations results depend heavily on the assumed start of the epidemic. most counties are simpler earlier in their epidemics under this assumption, but this requires . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . assuming a more disconnected country. flattening the curve appears to require some saturation of susceptible individuals and sufficient time. nevertheless, the overall pattern is robust, particularly with respect to the where returning recovered individuals to baseline behavior helps reduce cases. the ability to couple near real time behavioral data with demographic data to understand how behavior is shaping the covid- epidemic is critical for analyzing public health measures prioritizing testing, and developing back-to-work plans. by adapting the common seir framework to a dynamic time use structure that enables differential behavior by health we characterize the heterogeneity of covid- epidemic across the united states. the model is sensitive to initial conditions and parameterization, but still produces robust patterns. furthermore, the more the model is easily adjusted for local planning, and the analysis still provides an overview of the current situation. a substantial share of the behavior in us counties is sufficient to have flattened the curve (fig ) or is on a trajectory do so. flatten is a function of how long the epidemic has been going, behavior, the share of single person households, and population. indeed, some counties experience flatten curves without behavioral shifts. not all counties modeled as flattening the curve are actually experiencing flat curves. for example, fairfield county connecticut has experienced far more cases than the model predicts, but this county is tightly connected to new york county, new york, which has experienced a largely number of covid- cases. this shows how large well-connected counties can swamp the local behavior of surrounding areas. it will be important to account for these connections when considering back to work planning. nevertheless, a consistent pattern for most counties is that reverting to baseline behavioral will lead to a rapid rise in cases. there are a number of remote rural counties where if the epidemic took hold at the same time as the rest of their states, then irrespective of behavior the cases may already be on a decline. however, the model is likely less reliable for rural counties because the measure of time in public is likely not equivalent to that in suburban and rural counties. time in high risk locations, maybe a better measure than time at home. these are more likely to be complements (in the probabilistic sense) in suburban and rural areas, but less so in rural areas. results from rural counties should be treated with extreme caution. for counties still experiencing increasing numbers of infectious individuals (red and purple in fig ) , it is important to enhance the isolation of infectious individuals to reduce new cases. pcr testing should be prioritized in these counties. moreover, distancing measures will likely have to be maintained longer in these counties. indeed, counties that are bending the curve, but not flattening it will experience the longest epidemics. these will be the most difficult counties to get back to work, but these counties will likely experience less mortality (perhaps because of the arrival of therapeutic medicines) than if they reverted to baseline behavior. getting america back to work is important to reduce economic hardships but must be approached with caution to prevent excess mortality. there are hopes that serological testing will enable those with acquired immunity to return to work. however, once a credible serological test is available, it will likely be in short supply. maher et al. ( ) provide information on which counties are likely to suffer the . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . greatest hardships conditional on covid- epidemics. we show that an added benefit of disproportionally increasing the share of those with acquired immunity in public is that it also helps reduce cases -a double benefit. reducing the cases in large connected counties likely has spillover benefits to surrounding and connected counties. these counties should be prioritized for serological tests capable of identifying immunity, once such tests become available. we have focused on the first-order concern of targeting by health status. models that make use of timeuse data can be further refined by including other risk factors such as age, household size, and occupation. such models are under construction. nevertheless, two important caveats to smartphone driven time use models are that they likely perform best is suburban areas, then urban areas and worst in rural areas. furthermore, time-use data for children is very important but exceedingly hard to gather. this should be considered as the evidence mounts that schools for young children may be one of the safest locations to open first (viner et al., ) . we modify the standard seir (susceptible, exposed, infectious, and recovered) compartmental modelling structure in two ways to model social distancing. first, the model needs to account for inhome transmission, we do so by simplifying the age-and-household-structured model of (bayham and fenichel, ) . second, we modify the contact structure to allow for time varying time allocation and conditional proportional mixing (fenichel, ; fenichel et al., ) . additionally, we modify the disease induced mortality so that it is a function of prevalence or active cases in order to reflect exceedance of hospital capacity. the general model structure for population at time is we suppress time when doing so does not cause confusion. the specification of other parameters primarily come from wu et al. ( ) and are explained in table , but we conduct sensitivity analysis. the function in an index function adjusts the mortality fraction as a function when the number of active cases exceeds the hospital capacity. the first transmission term, ⋅ , models transmission outside the home. it is the standard transmission function where ⋅ is the conditional proportional mixing transmission function. lower case letters index their associated epidemiological compartments, and is the amount of time an individual case spends outside the home. in this formulation is the . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . probability that a susceptible individual becomes infected per minute contact with an infectious individual. when people avoid public spaces, they reallocate time to home. the second transmission term ⋅ models infections within the home. is the expected number of households that have infectious and susceptible individuals. assuming infectious status is independent of household size, the product of the first two factors on the right-hand side is the joint probability of a house having a susceptible and an infectious individual. this likely overestimates household transmission, which means that measures of distancing effectiveness are a lower bound. the third factor is the number of households. this makes home relatively safe when prevalence, ( / ), is low. ultimately, it is easier to think of and ℎ ℎ , where and ℎ are the preepidemic allocation to time outside and inside the home, with the shift from outside the home to inside the home. we do not attempt to provide realistic models of mortality. without an age structure it is unreasonable to accurately model deaths in a representative agent model when deaths are heavily skewed toward the elderly. this is left for future work. is often called a fundamental epidemiological parameter (chowell and brauer, ; cohen and enserink, ), but it is well known that, confounds the biological features of pathogen with human behaviors that lead to transmission (auld, ; fenichel et al., ; mossong et al., ; springborn et al., ; towers and chowell, ; zagheni et al., ) . therefore, is the more fundamental parameter that we expect to be approximately constant irrespective of local behavior. the derivation of involves taking the limit as → (chowell and brauer, ). the household transmission term goes to zero much faster than the public transmission term and has limited impact on the calculation of . therefore, / . bayham et al. ( ) calibrate time use with the american time use survey (atus) (hofferth et al., ) . using the atus data we find that the average american spent minutes outside the home per day in the years prior to the covid- epidemic, i.e., , with ℎ as the residual of the , minutes in a day (counting time spent in one's private car as time in the home), figure (s ). however, the atus data are not updated regularly enough to be useful in the rapidly evolving covid- epidemic. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . safe graph provides near real time (three day lag) estimates of time spent in home based on anonymized cell phone location data (safe graph, , www.safegraph.com) . these data provide the median time that cell phones are recorded in the phone's home location aggregated to census block group ( to , people). the data appear more reliable when aggregated to the county level. for the average county, safe graph tracks an average of , devices (fig s ) . according to the safe graph data, the average american (population weight by county average) spends . minutes at home per day. to calculate time in public, first we remove six hours of time as sleep that is unlikely to lead to new contacts (bayham et al., ) . this leaves minutes per day in public, which is similar to the atus data after accounting for the minutes the average american spends in a private car per day (fig ) . we use bilinski et al.'s ( ) mean estimate of (which they call ) for alameda, contra costa, marin, san francisco, san mateo, and santa clara counties in california, and divide by the population weighted for those counties of . minutes to determine . . is interpreted as the probability of infection per minute contact with an infectious individual. county level hospital capacity is available from homeland infrastructure foundation-level data (https://hifld-geoplatform.opendata.arcgis.com/. in our analysis we assume that % of cases will require hospital care. it is likely the far fewer cases are actually hospitalize, however disease induced mortality is not affecting the qualitative results of the model. we consider five epidemiological scenarios for every county in the united states. we assume the epidemic begins in every county days prior to the first reported case in the state with infectious individuals. first, we build a baseline scenario that is based on the average time use between january , and february , . this does not account for seasonal changes in behavior. if people are more likely to spend time out of the home as the weather warms, then our baseline is underestimating the counterfactual epidemic. second, we use the baseline behavior until the first case is reported in the state, and then impose the time series of actual time use in each county, but allowing individuals to revert to baseline behavior when the data end (currently april th ). by imposing the actual behavior we account for any public policy and compliance with that policy. third, we take the mean of the last five days of time use and continue that behavior. fourth, we mimic the third scenario but allow those recovered with immunity to return to baseline when the behavioral data end. fifth, we allow susceptible individuals and recovered individuals to return to baseline behavior, which is equivalent to reducing the time in public of exposed and infectious individuals, though not complete isolation. we classify counties into four groups: non-behaviorally responsive, curve benders, those with a flat curve, and curve flatteners. curve benders are counties where the number of infectious individuals over the last five days of observed safe graph time use data is less than using the baseline counterfactual scenario, whereas for non-behaviorally responsive counties this condition does not hold. a county has a flat curve if the slope of the infectious individuals curve over time is less than or equal to zero over the last five days of safe graph time use data. it is possible that counties have a flat curve, but have not adapted behavior. this happens in small counties. therefore, counties classified as curve flatteners satisfy the flat curve condition and the curve bender condition. we compute the number of avoided cases over the remainder of the epidemic by allowing recovered individuals to revert to baseline behavior relative to the case were current behavior is maintained for all. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . reliably calibrating a model of covid- is challenging given the large number share of undetected cases (bendavid et al., ; stock et al., ) and the detection rate varies through time. furthermore, the united states data does not provide a reliable record for calibration. the distribution of reported cases days after the first case in a county does follow a reasonable pattern (fig s ) . we perform two sensitivity analysis. first, we reduce the recovery rate from . to days. second, we start every counties epidemic days before the first report in each county. for counties not reporting epidemics we use the date that last county in the state first reported a case. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . however, values for rural counties in general are likely unreliable -this is a caution for using cell phone data. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . figure . illustrating three types of epidemiological trajectory, blue continued baseline behavior, yellow is based on cell phone data then reverting to baseline, green is continuing the current behavioral pattern, purple dots show what happens if recovered are allowed to revert to baseline behavior, and cyan is if both recovered and susceptible revert to baseline behavior. panel a is new york county, new york where if anything people are spending more time in public. panel b is queens county, new york, which has already created a hump. panel c is new haven county, connecticut, where behavioral shifts are reducing spread but not "flattening the curve." panel d is williamson county, texas. panel e is rockwall county, texas. panel f is forsyth county, georgia. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . figure . map of the status of different counties with respect to the behavioral effects on the covid- epidemic, bend means that behavioral shifts are reducing cases, but cases are still growing; bent.flat means that the behavioral shift is great enough such that new infections are declining; flat means new infections are declining but not because of behavioral shifts, no.change means that there is not a behavioral shift sufficient to reduce cases. figure s . the distribution of cases reported in a county days after the first case in that county is reported based on data from the new york times. the right tail is truncated, but we would have expected a mode much greater than . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . https://doi.org/ . how will country-based mitigation measures influence the course of the covid- epidemic? the lancet choice, beliefs, and infectious disease dynamics mathematical and statistical modeling for emerging and re-emerging infectious diseases measured voluntary avoidance behaviour during the a/h n epidemic covid- antibody seroprevalence the allocation of time and risk of lyme: a case of ecosystem service income and substitution effects defining high-value information for covid- decision-making the basic reproduction number of infectious diseases: computation and estimation using compartmental epidemic models as swine flu circles globe, scientists grapple with basic questions economic considerations for social distancing and behavioral based policies during an epidemic adaptive human behavior in epidemiological models time-varying covid- reproduction number in the united states american time use survey data extract builder: version . [dataset a covid- risk assessment for the us labor force covid- related social distancing measures and reduction in city mobility international comparisons of intensive care: informing outcomes and improving standards accounting for behavioral responses during a flu epidemic using home television viewing impact of week day social contact patterns on the modeling of influenza transmission, and determination of the influenza latent period are we# stayinghome to flatten the curve? school closure and management practices during coronavirus outbreaks including covid- : a rapid systematic review. the lancet child & adolescent health nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study using time-use data to parameterize models of the spread of close-contact infectious diseases key: cord- -xj ruz authors: jones, rodney p title: would the united states have had too few beds for universal emergency care in the event of a more widespread covid- epidemic? date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: xj ruz ( ) background: to evaluate the level of hospital bed numbers in u.s. states relative to other countries using a new method for evaluating bed numbers, and to determine if this is sufficient for universal health care during a major covid- epidemic in all states ( ) methods: hospital bed numbers in each state were compared using a new international comparison methodology. covid- deaths per hospital beds were used as a proxy for bed capacity pressures. ( ) results: hospital bed numbers show large variation between u.s. states and half of the states have equivalent beds to those in developing countries. relatively low population density in over half of us states appeared to have limited the spread of covid- thus averting a potential major hospital capacity crisis. ( ) conclusions: many u.s. states had too few beds to cope with a major covid- epidemic, but this was averted by low population density in many states, which seemed to limit the spread of the virus. the covid- pandemic has caught health systems around the world by surprise. covid- places a special burden on acute medical and intensive care beds [ ] [ ] [ ] . the world's largest economy, the usa, was also struggling to find the necessary resources to battle the virus. as with many countries, supplies of protective equipment and ventilators were initially in short supply [ ] . new york experienced an exceptionally large number of covid- deaths [ ] . are there any lessons to be learned from the outbreak so far within the context of a healthcare system in which both primary and secondary care are mainly resourced to deal with just insured patients [ ] ? this study will seek to evaluate if u.s. states had enough hospital beds to cope with a large epidemic across all parts of the country and will use a new method for comparing inter-and intra-national bed numbers to do so. for more than four decades economists have known that health care costs and resource usage escalate toward the end of life, more so than from age per se [ ] [ ] [ ] . this is especially so for hospital inpatient care with numerous studies demonstrating increased admissions and bed occupancy toward the end of life, which is moderately independent of the age at death [ ] [ ] [ ] [ ] . this has collectively been called the nearness to death (ntd) effect or the time to death (ttd) effect. one study indicated that while % of lifetime admissions occurred in the last year of life some % of bed occupancy occurred in this period [ ] . unfortunately, these relationships have never been incorporated into methods for forecasting healthcare demand and capacity planning. such methods almost exclusively rely on time series analysis or variants of demographic or age-based forecasting [ ] [ ] [ ] [ ] [ ] [ ] . the limitations of these methods are discussed elsewhere [ , [ ] [ ] [ ] [ ] [ ] [ ] . research into better methods for comparing hospital bed numbers between countries and regions has culminated in a new method which relies on the operation of the ntd effect [ , ] . based on this observation, bed numbers in different countries can be plotted on a graph showing beds per deaths (y-axis) versus the log of deaths per population (x-axis), also called the crude death rate. the deaths per population serve as a measure of age structure while beds per deaths reflects the role of nearness to death. this method avoids the limitations of simplistic international comparisons based on beds per population [ ] , which contains no adjustment for age structure or nearness to death. regarding the use of deaths per thousand population it should be noted that as far back as a relationship between bronchitis and emphysema (men aged [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] admissions per population and deaths per population had been demonstrated [ ] . in this new method a set of parallel lines (by changing the intercept) can be drawn which intersect the bed provision in different countries. the average for developed countries has the equation [ ] : beds per deaths = − . × ln(deaths per population), the country with the highest intercept is japan; however, this arises from ambiguity in the definition of a hospital bed where japan counts the equivalent to nursing home care in its definition of a hospital bed [ ] . the lowest bed availability in the developed world, where comprehensive health care is provided for the entire population, can be found in singapore and new zealand. this has been achieved by over years of government policy and policy implementation in integrated care [ , ] . for these two countries the intercept in the above equation is rather than for the international average. the method was validated at sub-national level using beds in the states of australia where a long-standing deficit in bed numbers in the state of tasmania was correctly quantified [ ] . the method has subsequently been confirmed to apply at local level using data for the populations covered by clinical commissioning groups in england (submitted). total hospital bed numbers have been used in this study because they are routinely available [ ] . the number of medical beds is not generally available except for several european countries and only up to the year [ ] . the health insurance system and population distribution in the u.s. places a set of constraints on physician and bed availability as resources follow a mix of population density and wealth, and not necessarily need [ ] [ ] [ ] . these issues are addressed further in the discussion section. in this analysis confirmed covid- deaths were from bing.com [ ] , total hospital bed numbers include adult and pediatric acute care, plus maternity and mental health. international total hospital beds were from the world bank [ ] , total hospital beds by us state was from the kaiser family foundation [ ] , while the number of acute beds by us state was from the american hospital directory [ ] . available beds are beds staffed to receive patients. state population and median household income was from united states census bureau [ , ] . proportion rural population and rural poverty were from the us department of agriculture [ ] . land use was from the national park service [ ] . deaths in u.s. states was from the centers for diseases control and prevention (cdc) wonder database [ ] . weighted population density was from decision science news [ ] . all data is publicly available but can be obtained on request from the author. all data was manipulated, and charts prepared using microsoft excel. covid- deaths per bed was calculated by dividing deaths (at the th of june) by total hospital bed number as in the data sources. adjusted bed number by state was calculated as the higher of two methods as follows. total hospital bed numbers [ ] were compared to acute bed numbers [ ] . the former is from a non-mandatory survey while the latter are mandatory for medicare. the ratio of one to the other was calculated for each state. the median value of this ratio was % higher for total hospital beds. in states, total hospital beds were lower than acute beds and in those states the higher of total hospital beds or acute beds times . was used in this study. beds in some mental health hospitals or smaller community hospitals may have been missing from the count of total beds. all other numbers are derived by simple division of one parameter by the other, i.e., covid- deaths per total hospital beds. international data in figure was from previous studies on this topic [ , ] while the parameter adjusted beds per deaths is detailed in previous studies [ , ] . all data was manipulated, and charts prepared using microsoft excel. covid- deaths per bed was calculated by dividing deaths (at the th of june) by total hospital bed number as in the data sources. adjusted bed number by state was calculated as the higher of two methods as follows. total hospital bed numbers [ ] were compared to acute bed numbers [ ] . the former is from a nonmandatory survey while the latter are mandatory for medicare. the ratio of one to the other was calculated for each state. the median value of this ratio was % higher for total hospital beds. in states, total hospital beds were lower than acute beds and in those states the higher of total hospital beds or acute beds times . was used in this study. beds in some mental health hospitals or smaller community hospitals may have been missing from the count of total beds. all other numbers are derived by simple division of one parameter by the other, i.e., covid- deaths per total hospital beds. international data in figure was from previous studies on this topic [ , ] while the parameter adjusted beds per deaths is detailed in previous studies [ , ] . beds per population has been used to compare international bed numbers for many years and hence it is useful to see how this compares with beds per deaths. such a comparison is given for us states in figure where it can be seen that, as expected, there is a degree of relationship between the two, such that, beds per deaths is approximately equal to × beds per population. typically, younger populations lie above the trend line while older ones lie below. applying the same approach to international data [ ] gives a trend line with a slope of as the international average (data not shown). however, a series of lines describe the international data with a slope ranging from (mainly russia and former soviet countries and also west virginia in figure ) to (encompassing most countries), through to (kuwait, bahrain which have the youngest populations and the least deaths per population). beds per population has been used to compare international bed numbers for many years and hence it is useful to see how this compares with beds per deaths. such a comparison is given for us states in figure where it can be seen that, as expected, there is a degree of relationship between the two, such that, beds per deaths is approximately equal to × beds per population. typically, younger populations lie above the trend line while older ones lie below. applying the same approach to international data [ ] gives a trend line with a slope of as the international average (data not shown). however, a series of lines describe the international data with a slope ranging from (mainly russia and former soviet countries and also west virginia in figure ) to (encompassing most countries), through to (kuwait, bahrain which have the youngest populations and the least deaths per population). while beds per deaths is a useful comparator the new method has the advantage that it uses both deaths and population to compare bed provision (next section). figure shows a plot using data for u.s. states in using the new method which also includes lines for the international average for developed countries, and for new zealand and singapore. data for canada (red diamond) and the uk (purple triangle) are also shown for comparison as examples of low bed number countries offering universal health care. canada and the uk lie on a line parallel to but above that for new zealand and singapore. the data point for the entire usa is the red square. all us states, except for the federal district of washington d.c. (district of columbia) and to a less extent south and north dakota, have far fewer hospital beds that the average for developed countries, while several states (washington, oregon) have less beds than the average for the less developed countries. around half of u.s. states are below the most bed efficient line for universal care in singapore and new zealand. while beds per deaths is a useful comparator the new method has the advantage that it uses both deaths and population to compare bed provision (next section). figure shows a plot using data for u.s. states in using the new method which also includes lines for the international average for developed countries, and for new zealand and singapore. data for canada (red diamond) and the uk (purple triangle) are also shown for comparison as examples of low bed number countries offering universal health care. canada and the uk lie on a line parallel to but above that for new zealand and singapore. the data point for the entire usa is the red square. all us states, except for the federal district of washington d.c. (district of columbia) and to a less extent south and north dakota, have far fewer hospital beds that the average for developed countries, while several states (washington, oregon) have less beds than the average for the less developed countries. around half of u.s. states are below the most bed efficient line for universal care in singapore and new zealand. for comparison, the international range in deaths per population is from around . in the oil rich gulf countries through to in sierra leone. the uk has a ratio of . [ ] . countries near to the less developed countries average are colombia, ecuador, and algeria. around % of us states lie close to this line. despite the lower slope for the line describing the less developed countries (equation ( ) for comparison, the international range in deaths per population is from around . in the oil rich gulf countries through to in sierra leone. the uk has a ratio of . [ ] . countries near to the less developed countries average are colombia, ecuador, and algeria. around % of us states lie close to this line. despite the lower slope for the line describing the less developed countries (equation ( ) above), over the limited range in deaths per population seen in us states ( . in utah to . in west virginia), the two equations are almost parallel and the equation for developed countries can be applied to adjust all countries to the us average of deaths per population (next section). the average line for the least developed countries has the equation (analysis not shown): beds per deaths = − × ln(deaths per population), the line for the least developed countries lies below the scale in figure and includes countries such as sierra leone, madagascar, senegal, niger, etc. by adjusting all u.s. states to the average deaths per population for the u.s., namely . , and adjusting world countries to the same number allows direct comparison between u.s. states and their nearest international equivalent. this comparison is given in table for the states with the least number of beds which are at or below the u.s. average. as can be seen oregon has equivalent beds to burundi, washington (not to be confused with washington d.c.) to costa rica, california has equivalent to albania, and colorado has equivalent to algeria. the average for the usa is equivalent to vanuatu. such low levels of bed provision clearly indicate that large parts of the u.s. may be susceptible to a major epidemic and specific issues relating to covid- will now be investigated. the possibility that covid- transmission may have been reduced in those states with lower population density is investigated in figure . the possibility that covid- transmission may have been reduced in those states with lower population density is investigated in figure . [ ] to adjust for the fact that the surface area of most states is largely devoted to agriculture, forestry, or national parks. for example, there are , km of national parks [ ] which represent . times the size of the united kingdom. most of the population therefore experience a far higher (weighted) population density than the simple division of population by land area. in figure , covid- confirmed cumulative deaths were up to the th june [ ] , while deaths in [ ] (the most recent data available for the u.s.) were taken as the baseline per annum deaths in the absence of covid- . hence excess covid- deaths as a percentage of total deaths. as can be seen in figure low population density is generally associated with lower excess covid- confirmed mortality. mortality generally rises for state weighted population density above persons per mile ( persons per km ). virus transmission in an epidemic always leads to a granular spatial distribution of cases [ ] . the major focus of the covid- epidemic in the u.s. was the heavily populated north east corner, with new york receiving the fifth highest number of international visitors in the u.s. [ ] . in the absence of international hospital admissions due to covid- the cumulative deaths per hospital bed can be used as a measure of potential capacity pressure upon available beds. figure shows the relationship between cumulative deaths per bed and cumulative excess mortality for us states. as can be seen states had less than covid- deaths per beds ( %) over the -day period march to june which reflects the lower covid- cases and deaths in those states with lower populations density. while new york received international attention due to the high number of deaths figure shows that new jersey, massachusetts, and connecticut all % % % % % % % % % % , , , state weighted population density per square mile [ ] to adjust for the fact that the surface area of most states is largely devoted to agriculture, forestry, or national parks. for example, there are , km of national parks [ ] which represent . times the size of the united kingdom. most of the population therefore experience a far higher (weighted) population density than the simple division of population by land area. in figure , covid- confirmed cumulative deaths were up to the th june [ ] , while deaths in [ ] (the most recent data available for the u.s.) were taken as the baseline per annum deaths in the absence of covid- . hence excess covid- deaths as a percentage of total deaths. as can be seen in figure low population density is generally associated with lower excess covid- confirmed mortality. mortality generally rises for state weighted population density above persons per mile ( persons per km ). virus transmission in an epidemic always leads to a granular spatial distribution of cases [ ] . the major focus of the covid- epidemic in the u.s. was the heavily populated north east corner, with new york receiving the fifth highest number of international visitors in the u.s. [ ] . in the absence of international hospital admissions due to covid- the cumulative deaths per hospital bed can be used as a measure of potential capacity pressure upon available beds. figure shows the relationship between cumulative deaths per bed and cumulative excess mortality for us states. as can be seen states had less than covid- deaths per beds ( %) over the -day period march to june which reflects the lower covid- cases and deaths in those states with lower populations density. while new york received international attention due to the high number of deaths figure shows that new jersey, massachusetts, and connecticut all experienced higher potential bed demand while rhode island experienced intermediate potential demand. washington d.c. experienced relatively lower bed demand due to the high number of hospital beds in this federal district. experienced higher potential bed demand while rhode island experienced intermediate potential demand. washington d.c. experienced relatively lower bed demand due to the high number of hospital beds in this federal district. the relatively low population density in most us states seemingly averted a catastrophic covid- bed capacity overload. while many countries seek to develop a coordinated universal healthcare system, healthcare in the us is largely left to market forces [ ] . medicaid and medicare provide some basic care to the poor and elderly, government workers and the military are covered by state and federal government schemes while the rest of the population is covered by private insurance via their employer or themselves, or to remain uninsured. medicaid and medicare recipients can take out additional insurance to complement the basic government scheme. [ , ] . there are over medical insurers offering a complex variety of schemes with different terms and conditions [ ] . hospitals can be either for-profit or not-for-profit and are either independent, state owned or part of larger chains, and are free to make their own planning decisions regarding bed numbers. some % of the us population lives in a rural area (range % washington d.c., new jersey, delaware to % in wyoming), . % of the rural population lives below the poverty threshold (range . % in connecticut to . % in arizona) [ ] . rural populations in the us are known to access hospital services less than their urban counterparts due to distance and poverty [ ] . however, even in the densely-populated uk with free access to healthcare, rural populations have % lower hospital bed occupancy than their urban counterparts [ ] . the rural population is served by a multitude of small community hospitals, such that half of us hospitals have fewer than beds [ ] . in that us average was acute beds per hospital (range in wyoming to in new jersey and connecticut and in new york) [ ] the relatively low population density in most us states seemingly averted a catastrophic covid- bed capacity overload. while many countries seek to develop a coordinated universal healthcare system, healthcare in the us is largely left to market forces [ ] . medicaid and medicare provide some basic care to the poor and elderly, government workers and the military are covered by state and federal government schemes while the rest of the population is covered by private insurance via their employer or themselves, or to remain uninsured. medicaid and medicare recipients can take out additional insurance to complement the basic government scheme. [ , ] . there are over medical insurers offering a complex variety of schemes with different terms and conditions [ ] . hospitals can be either for-profit or not-for-profit and are either independent, state owned or part of larger chains, and are free to make their own planning decisions regarding bed numbers. some % of the us population lives in a rural area (range % washington d.c., new jersey, delaware to % in wyoming), . % of the rural population lives below the poverty threshold (range . % in connecticut to . % in arizona) [ ] . rural populations in the us are known to access hospital services less than their urban counterparts due to distance and poverty [ ] . however, even in the densely-populated uk with free access to healthcare, rural populations have % lower hospital bed occupancy than their urban counterparts [ ] . the rural population is served by a multitude of small community hospitals, such that half of us hospitals have fewer than beds [ ] . in that us average was acute beds per hospital (range in wyoming to in new jersey and connecticut and in new york) [ ] . the us average occupancy rate for acute hospital beds is % (range % in wyoming with % rural population to % in washington d.c. with % rural population) [ ] . the smallest hospitals tend to occur in the states with the lowest average income [ ] . the small size of u.s. hospitals imposes low average occupancy [ ] , and higher unit costs [ ] , leading to hidden barriers to access acute care. hence healthcare in the u.s. is what many may regard as overly complex and with little government intervention to ensure universal health care. generally poorer rural populations seek less acute care, which is then compounded by low population density leading to small hospital size with resulting marginal commercial viability. hence the generally low bed numbers in figures and and table and the difficulty in explaining exactly which factors contribute to low bed numbers in some states. as demonstrated in figure around % of u.s. states fall below the line for new zealand and singapore. states lying below the line for new zealand and singapore has bed availability levels equivalent to the "less developed" countries where universal health care is also not available [ , ] . lowest bed availability occurs in oregon. the netherlands and australia have total beds near the international average. australia has a higher proportion of rural population than the u.s. [ ] , and rurality per se cannot be an explanatory factor for the low number of u.s. hospital beds. washington d.c. which has some of the most prominent hospitals and research institutes, has the highest number of physicians per capita, the highest median household income, and only . % of persons are uninsured [ , ] . washington d.c. is probably the closest approximation to universal healthcare in the u.s. countries like germany and austria which have -times the u.s. average number of beds [ ] can manage a surge event such as covid- with far greater ease [ ] . it is well recognized that the u.s. healthcare industry only represents a proportion of the population and hence comparative international health outcomes are poor [ , ] . this is confirmed by the low levels of hospital bed provision in figures and while data on the number of medical beds in the us and elsewhere is not available it is obvious that the number of these beds must be lower than the total beds. for example, in england available mental health beds account for % of total hospital beds while maternity accounts for a further % [ ] , the medical group of specialties accounts for % of total occupied beds [ ] . research suggests that the demand for medical beds is directly proportional to the number of total deaths and has a far flatter slope than figure [ ] . the average number of available (staffed) medical beds per deaths across europe was [ ] , with a -year average of ± (±standard deviation) occupied medical beds per deaths in england [ ] . in england medical beds operate at over % average occupancy [ ] . some us states have barely enough total beds to accommodate just the medical group of patients under universal health care. as in other countries, the us did shut down routine surgery to create space for covid- patients [ ] ; however, the basic position of too few beds remains an overriding problem. the major impact of covid- has been the high use of critical care beds [ , ] . as with medical beds, research shows that critical care bed requirements are likewise directly proportional to the number of deaths [ ] . the u.s. has the highest number of critical care beds per population in the world [ ] but did need additional critical care beds to service covid- hot spots. under normal circumstances the poorer communities (not covered by medicaid) affected by covid- would not have been able to access hospital care [ , ] , and many with health insurance, especially the elderly, would not seek medical care due to the risk of bankruptcy due to co-payments [ ] [ ] [ ] [ ] . this would have acted to further spread the disease. on the april president trump announced a covid- support package in which the inpatient care of uninsured persons suffering from covid- would be covered by the federal government [ ] . some insurers have also announced that co-payments would be waived. however, it is unclear how effectively this has been communicated and if hidden barriers to access remained such as access to covid- testing and fear of a high bill for attending the emergency department should the illness not be due to covid- . indeed, those recently unemployed appear to fall into a policy gap [ ] . a recent study has used age-specific mortality patterns along with population demographic data to map projected burden of covid- and the associated cumulative burden on the healthcare system (total hospital beds and intensive care beds) at county level in the us for a scenario in which % of the population of each county acquired infection. it was suggested that per capita disease burden and relative healthcare system demand may be highest away from major population centers where there are the fewest hospital and critical care beds [ ] . the states identified in this study roughly align with those identified by miller et al. [ ] simply because too few beds, mainly located in large cities, are an inescapable limitation to treating covid- patients requiring hospitalization. figures and shows the resulting granular distribution of covid- confirmed deaths. states with extremely low bed provision such as oregon were spared from a potential medical disaster by virtue of low incidence of cases relative to available beds. the u.s. has a somewhat unique population distribution. only five cities (including new york at , per square mile) have a weighted population density above , persons per square mile [ , , , ] . by comparison london has a weighted density of , per square mile and some % of the population in england live at greater than , persons per square mile [ ] . much of the remainder of u.s. has low population density. population density is a critical factor in disease and covid- transmission [ , ] . this association for covid- has been observed in english local authorities [ ] , and in england and wales the age-standardized covid- mortality rate in urban major conurbations was -times higher than in rural hamlets [ ] . figure showed the relationship between the ratio of confirmed covid- deaths (at april ) per population versus the weighted population density for each state. weighted population density is the effective population density experienced by the average person in the state [ , ] . weighted population density considers that most people live in cities and towns hence the population density that they experience is much higher than the simple division of population by total land area. hence this is between to times higher than the raw density [ , ] . population density is not the only factor responsible for spread of covid- and factors such as international exposure, household crowding and mass gatherings will also play a role [ , ] . while the extent of covid- testing varies between us states, figure nevertheless establishes an important precedent. as demonstrated the states with lowest weighted population density all experience low death rates. these states tend to have fewer hospitals simply because a hospital needs a high population within a reasonable travel distance to be financially viable. hence low weighted population density in over half the states has acted to avert a medical disaster in the usa. given the complexities of healthcare in the u.s. discussed in section . the issue of exactly why some states have such low bed numbers has no easy answer. one study has demonstrated that the average number of beds per hospital was related to average state income [ ] . average length of stay in each state was related to average number of beds per hospital, being generally lowest in those states with the smallest hospitals, and lowest average income [ ] . another study demonstrated that the number of bed days per death (or occupied beds per deaths) rose with population density [ ] . population density and proportion rural population are interrelated, and it would therefore seem that urban populations seem to make greater use of hospital care at the end of life. in past decades the u.s. was able to claim that lower length of stay (los) was an explanation for fewer beds; however, in recent years los in many countries is now reasonably close to or lower than that in the u.s. [ , ] and this can be dismissed as an explanatory factor. hence the reason why oregon, a mainly agricultural state focusing on horticulture ( % rural, % rural poverty) has so few beds is a complex mix of numerous factors which seem not to have been adequately investigated, and which are largely irrelevant in the context of the u.s. health care industry. the proportion of persons who are insured is probably an overly simplistic indicator since insurance policies issued by insurers can have widely different terms and conditions. a simple overview is that in the u.s. healthcare resources follow "money" rather than "need" and this is then distorted by population density, or more correctly population distribution. due to the absence of numbers of persons admitted to hospital for covid- the total confirmed covid- deaths has been used as a proxy measure. clearly persons die of covid- in nursing homes [ ] and at home; however, this is probably a reasonable proxy for hospital capacity pressure since death is most likely to occur in older people who are most represented in covid- admissions [ , ] . in new york it was recognized that elderly covid- patients were overly rapidly discharged into nursing homes, which led to cross-infection and further compounded the number of deaths [ ] . the same hasty discharge into nursing homes occurred around the world [ ] . covid- deaths are themselves an underestimate due to variable testing capacity between states and the real excess mortality may be % higher [ ] ; however, the available data must be used to make comparisons despite its limitations. the second limitation is the use of total hospital beds to compare between states and countries. once again given the lack of detailed international data covering just acute beds this is a reasonable proxy. the issue of international hospital bed number comparisons is highly topical and the new method for bed comparison is an improvement on the former simplistic beds per population. the new method should be used to delve further into the reasons why different healthcare systems operate with such widely varying bed numbers. factors such as population density, average hospital size, and rurality need to be given greater prominence. a new method for comparing international bed numbers has been used to give greater insight into the variation in bed numbers between u.s. states. decades of focus on providing medical resources to the insured, along with high levels of co-payment imposed by insurers to discourage use of those resources [ ] [ ] [ ] [ ] has left the us with very a very wide range in bed provision between states and generally low levels of hospital beds in relation to other developed countries. some states have numbers of beds equivalent to those in less developed countries. despite extremely low bed numbers in many states the u.s. was spared from a full-scale disaster due to concentration of cases in a few states with relatively high bed numbers. the healthcare "system" in the us is in a seemingly intractable dilemma from which it is difficult to extract itself and which leaves it open to the impact of future pandemics should they occur with a different spatial distribution or mode of transmission to covid- . indeed, statistics indicate that spread of covid- has increased in recent days [ ] . the demand for inpatient and icu beds for covid- in the us: lessons from chinese cities. harvard university. . available online characterization and clinical course of patients with coronavirus disease in new york: retrospective case series forecasting critical care bed requirements for covid- patients in england, cmmid repository covid- : the crisis of personal protective equipment in the us com coronavirus (covid- ) statistics. higher spending, worse outcomes? the commonwealth fund the high cost of dying medical care at the end of life: diseases, treatment patterns, and costs counting backward to health care's future: using time-to-death modelling to identify changes in end-of-life morbidity and the impact of aging on health care expenditures hospital care for the elderly in the final year of life: a populationbased study use of acute hospital beds does not increase as the population ages: results from a seven-year cohort study in germany hospital admissions, age, and death: retrospective cohort study use of health services in the last year of life and cause of death in people with intellectual disability: a retrospective matched cohort study hospital use by an ageing cohort: an investigation into the association between biological, behavioural and social risk markers and subsequent hospital utilization models for forecasting hospital bed requirements in the acute sector a methodology for estimating hospital bed need in manitoba in comparison of different methods to forecast hospital bed needs how many beds? capacity implications of hospital care demand projections in the irish hospital system forecasting hospital bed needs the demography myth-how demographic forecasting underestimates hospital admissions and creates the illusion that fewer hospital beds or community-based bed equivalents will be required in the future growth in nhs admissions and length of stay: a policy-based evidence fiasco condition specific growth in occupied beds in england following a sudden and unexpected increase in deaths have doctors and the public been misled regarding hospital bed requirements? hospital beds per death how does the uk compare globally a pragmatic method to compare hospital bed provision between countries and regions: beds in the states of australia hospital beds (per thousand people) acute care hospital beds, medical group of specialties, world health organisation unequal distribution of the u.s. primary care workforce population density and healthcare costs average length of stay in hospitals in the usa hospital beds per population by ownership type, kaiser family foundation the american hospital directory. hospital statistics by state. ahd. . available online median household income by us state, us census bureau united states department of agriculture. state fact sheets deaths in us states weighted population density, decision science news on the predictability of infectious disease outbreaks the most visited states in the u.s.; world atlas overview of the united states healthcare system largest health insurance companies of understanding shortages of sufficient health care in rural areas demand for hospital beds in english primary care organisations hospital bed occupancy demystified and why hospitals of different size and complexity must operate at different average occupancy a guide to maternity costs-why smaller units have higher costs demography and population us states with the most hospital beds, world atlas too little or too much? missing the goldilocks zone of hospital capacity during covid- us: address impact of covid- on the poor, human rights watch bed availability and occupancy data-overnight how many medical beds does a country need? an international perspective elective surgeries set to resume, with complications and concerns. nbc news trends in critical care bed numbers in england variation in critical care services across north america and western europe medical bankruptcy and the economy, the balance the health of private insurance in the us during covid- understanding a health insurance copayment. ehealth increased ambulatory care co-payments and hospitalizations among the elderly government will pay for uninsured americans' coronavirus treatment: trump, the new york post mapping the burden of covid- in the united states density calculations for u.s. urbanized areas, weighted by census tract, austin contrarian on population-weighted density mapping risk factors for the spread of covid- in africa, africa centre for strategic studies the disconcerting association between overpopulation and the covid- crisis, the times of israel how many extra deaths have really occurred in the uk due to the covid- outbreak? vii. infectious granularity, research gate deaths involving covid- by local area and socioeconomic deprivation: deaths occurring between length of stay in hospital: how countries compare length of hospital stay mortality associated with covid outbreaks in care homes: early international evidence. article in ltccovid.org, international long-term care policy network existing conditions of covid- cases and deaths factors associated with hospital admission and critical illness among people with coronavirus disease health officials ordered coronavirus patients to nursing homes despite empty beds estimation of excess deaths associated with the covid- pandemic in the united states funding: there are no sources of funding. the author declares no conflict of interest. key: cord- -keso oh authors: leroy, suzanne a.g. title: natural hazards, landscapes and civilizations date: - - journal: reference module in earth systems and environmental sciences doi: . /b - - - - . - sha: doc_id: cord_uid: keso oh a series of case studies, derived from holocene palaeoenvironmental investigations, archaeology, and history, are used to analyze ancient natural hazards and their impact on societies. the evolution of societies is inscribed in geomorphology, as a close relationship exists between the landscape and humans. four factors underpin disasters: time, space, type of society, and type of event. in some cases, disasters apparently caused civilization to collapse, but, in other cases, they have spawned innovations and led to more resilient societies. in the face of landscape change, our modern society should not be lured by technology and globalization, as these could become more sources of vulnerability than of prevention and mitigation. changes always have a cost. civilizations have always had difficulties coping with the element of surprise in a hazard; this will remain uncontrollable. if a natural hazard occurs in a restricted area of the planet, its impact may be felt worldwide due to our current great interconnectedness. slow change or a series of disasters . the younger dryas period and the initiation of agriculture . the mid-holocene end of the green sahara past great disasters . the black sea flood and the spread of indo-european people . the first intermediate period in the pharaoh dynasties and the . ka global event . the moche collapse in peru in about ad . the classical maya decline about ad in central america . the norse greenland demise at the beginning of the little ice age . the colonization of pacific islands recent disasters . the volcanic eruption of laki in ad - . the ad krakatau eruption and indonesia independence factors leading to disaster . positive effects of sudden environmental changes . is modern society vulnerable to rapid environmental change? . towards solutions conclusions disasters and catastrophes are considered in this article, but some slower phenomena that have had huge geomorphic and environmental impacts with long-lasting effects on civilization are also addressed. the case studies presented in this article are derived from archaeology, historical data, and recent events and are taken from the past , years. they are spread over north and south america, the north atlantic, southeast europe and southwest asia, north africa, oceania, and the indian ocean (fig. ) . although most of the examples are accepted by the scientific community, some continue to be debated, for example the black sea flood. past natural hazards and their consequences remain nevertheless sources of valuable lessons, even if the fine details cannot be confirmed. in this section, two examples of large-scale environmental changes are examined. they appear to take place over several centuries, but actually are the cumulative effect of small disasters. the two examples illustrate the concept of catastrophe, as no return to the previous state of conditions is possible. plant cultivation was first practiced during the younger dryas, a brief period from , to years before christ (bc), or , - , years ago (brauer et al., ) . this period corresponds to a brief return of the ice ages, i.e., an unexpected global worsening of climatic conditions. global temperature suddenly dropped by several degrees celsius (alley, ) . the changes at the beginning and at the end of the younger dryas took place stepwise over several decades. however recent research suggests that stepped changes in climate happened within years only (brauer et al., ; steffensen et al., ) . drying in the middle east ( fig. ) during the latter part of the younger dryas coincide with the late epipalaeolithic period and the late natufian culture (meadows, ) . the archaeology of the middle east indicates that, prior to the beginning of the younger dryas, dense populations of hunter-gatherers had some year-round settlements (fuller, ) . primitive forms of barley and wheat were gathered and eaten by these people before the advent of cultivation. during the younger dryas, most of the permanent sites were abandoned, but some groups maintained sedentary lifestyles in order to tend cereal crops. this progressively induced a selection towards non-brittle rachis (flower stalk) essential for domestication, which allows easier harvest owing to the absence of the natural and unfavorable property of seed shattering (purugganan and fuller, ) . after the younger dryas, villages reappeared and many of these groups were cultivators. finds of domesticated plants then became generally widespread in the neolithic (purugganan and fuller, ) . plant domestication has been attributed to a decrease of annual yields of wild cereal stands caused by climatic stress, which created the need and the motivation for cultivation. it seems likely that climatic change before and during the younger dryas played greenland, : laki, : sahara, : egypt, : middle east, : black sea, : aceh, : krakatau. an essential role (byrd, ; willcox et al., ; blockley and pinhasi, ) . concomitant cultural and social changes (mithen, ) led to a dramatic change in lifestyles and laid the foundations for the early civilizations of mesopotamia and egypt. many large lakes formed in the sahara at the beginning of the holocene ( , years ago) ( fig. ) (de menocal et al., ; hoelzmann et al., ) . this period of desert greening is referred to as the african humid period (ahp). precipitation was perhaps as much as times higher than today (petit-maire, ; renssen et al., ) . the monsoon summer rain played a key role in the greening of the sahara. more summer radiation at the beginning of the holocene, due to a milankovitch-driven insolation maximum, warmed the continent, producing more monsoon rain (ruddiman, ) . an important megafauna, including giraffes, hippopotami, elephants, zebras, cattle, and horses, lived in what is now a desert (fig. ). they were supported by grassland now typical of the sahel, which at that time extended several hundreds of kilometers farther north. during the early holocene, this region was occupied by pastoral societies that practiced some agriculture (hoelzmann et al., ; kuper and kroepelin, ) . after the mid-holocene, less solar radiation caused the winter monsoon to strengthen, keeping potential rains away from the continent (ruddiman, ) . the modeled mid-holocene transition in the western sahara from wet to dry is highly non-linear, with centennial-scale climatic fluctuations due to the biogeophysical feedback between precipitation and vegetation cover (renssen et al., ) . therefore, climate oscillated sharply at the ahp termination (renssen et al., ) . the saharan-sahelian population around - years ago lived in a rapidly changing environment and experienced a succession of increasingly stressful periods of lower precipitation. as north africa dried, the pastoral lifestyle became too uncertain because of unpredictable summer rainfall. thus pastoral societies of the sahara migrated to refugia such as the nile valley, the sahel, and the saharan highlands, where they made a vital contribution to many subsequent african cultures, including pharaonic egypt (brooks et al., ; kuper and kroepelin, ) . permanent settlements and agriculture in the nile valley were preferably adopted with the support of irrigation (brooks, ) . water deficits and excesses have played a large and often decisive role in the development of ancient civilizations, especially when the crisis lasted longer than the society's resilience capacity. rapid changes in coastline position and in lake levels are the foundation of many ancient myths and religions; examples include the gilgamesh flood and noah flood. droughts have been invoked to explain the collapse of many civilizations such as the ancient egyptian dynasties, the akkadian empire in ancient mesopotamia, and the harappans in northwestern india and pakistan. the americas have seen many native indian societies develop and decline, to be reborn elsewhere in different forms. true collapse did not take place; rather there were expansions and retractions, such as for the ancestral puebloans in the southwestern united states, the central american maya, and the south american moche. delicately balanced nature-human interactions occur when pre-industrial societies settled in pristine environments. these societies modified, and sometimes greatly damaged, these environments with the possibility of negative returns. these environmental disasters may have additionally coincided with climatic changes and contributed, for example, to the abandonment of the norse settlements in greenland and to the cultural and environmental collapse on islands in oceania. at the end of the pleistocene, large amounts of meltwater from the eurasian ice sheet were carried southward into the black sea ( fig. ) by rivers such as the don, dnieper, and volga, and also from the caspian sea and lakes farther east and northeast. this inflow maintained the black sea at a level much higher than the mediterranean sea and produced a strong outflow into the mediterranean sea via the marmara sea. during the early holocene, meltwater discharge into the black sea ceased, and the climate became drier; this phase is recognized in southeastern europe and farther east in central asia (wright et al., ) . the level of the black sea dropped below the bosphorus sill, perhaps by as much as m. ryan et al. ( ) and ryan and pitman ( ) argued that the black sea, which was then a slightly brackish lake, was suddenly flooded by mediterranean waters around years ago. this catastrophic event, which has been called the black sea flood or even noah flood, is marked by a change in sedimentation as well as a faunal turnover in the black sea due to the change of salinity. water levels would have risen by up to cm per day, causing a rapid inundation of low-gradient surfaces. all economic activities around the black sea were directly impacted. people migrated away from the coast and river estuaries, now submerged canyons, where it is thought most of the settlements were located. the impact of this flood on people has been hotly debated; some have suggested that it was the impetus for the expansion of neolithic farming into europe, perhaps even linked to the synchronous spread of the indo-european language (ryan and pitman, ) . however, arguments persist about the date of the flood and the level of the black sea before it was reconnected to the mediterranean sea, and thus the speed of water-level rise (ryan, ; yanko-hombach et al., ) . one interesting scenario that links all aspects of this event is the bursting of glacial lake agassiz in northern north america about - years ago. this outburst flood sent a massive amount of meltwater into the world's oceans, raising sea level by . m (clarke et al., ; turney and brown, ) . as the mediterranean sea rose, it would have breached the bosphorus sill, initiating the flooding of the black sea, and the subsequent spread of neolithic farmers and indo-european culture (turney and brown, ) . within the span of two millennia following the adoption of an agricultural mode of life in egypt (fig. ) , communities began to coalesce in progressively larger social groups (hassan, ) . by years bc, egypt was unified in a single state ruled by kings who launched pyramid-building programs that were indicative of a strongly centralized government and of general prosperity. this period coincided with bountiful nile river floods (hassan, ) and therefore abundant grain harvests. the pharaohs claimed authority based on their supposed ability to intercede with the gods to supply the annual nile river floods (fagan, ) . when harvests failed for several decades, the power of the pharaoh declined and the old kingdom collapsed. the old kingdom, the middle kingdom, the new kingdom, and the late period are separated by intermediate periods of political and social chaos that may have been caused by drought produced by failed rainfall upstream in the nile river watershed. this link is particularly evident for the first intermediate period (c. - years bc). a -year period of drought began around bc as an el-niño drought struck the ethiopian headwaters of the nile. in fact the river flow became so low that people in egypt could walk across it. in the face of grain shortages, the central government of egypt fell apart, local warlords seized control, and people suffered from severe famine. it took years for egypt to reunify and subsequent pharaohs invested massively in irrigation and grain storage to avoid the fate of their improvident predecessors (hassan, ; fagan, ) . hassan ( ) correlated low water levels of lake fayium, a large nile-fed lake southwest of the nile river delta, with this intermediate period. stanley et al. ( ) analyzed sediments obtained from drilling at the center of the nile delta and identified a thin layer of reddish-brown silt dating to between and years bc, coincident with the time of the collapse of the old kingdom. they attributed this layer to weathering of the delta plain during a long period of drought. the crisis in egypt in years bc, or years ago, coincides with other civilization collapses from egypt to china. drought affected the harappan and akkadian civilizations in mesopotamia and the indus river basin, respectively, and exceptionally cold weather affected the longshan culture in china (weiss and bradley, ; gao et al., ) . a regional advance of alpine glaciers in western north america has been observed at . ka (menounos et al., ) . the . ka event is recognized as one of the few global events (staubwasser and weiss, ) ; therefore its impact corresponds well to that of a catastrophe rather than a disaster. pre-columbian coastal and highland peruvian civilizations ( fig. ) offer exceptional insight into past linkages between culture and climate change because they sustained densely populated and complex agrarian cultures in challenging environments (de menocal, ) . the moche civilization developed in valleys draining west to the pacific ocean in northern peru, between about and after christ (anno domini or ad). these valleys had no upstream glaciers; therefore the moche were dependent on local precipitation. the moche had a hierarchical society consisting of warrior priests, doctors, artisans, and the mass of the agricultural population. the leaders sacrificed their prisoners of war in an attempt to control the weather. the moche developed sophisticated irrigation systems linking numerous valleys, metallurgy, urban centers, and monumental adobe brick structures. they controlled the entire northern peruvian coastline south of the sechura desert (chapdelaine, ) . although the western slopes of the andes are among the driest places on earth, the adjacent pacific ocean is a rich fishery. the sea provided sufficient resources to support large sedentary populations. agriculture in the lowlands demanded large irrigation canals to control runoff from the andes. in the highlands, agriculture and pastoralism became increasingly important, in part to supplement the local lowland coastal resources such as salt, fish, and seaweed. the formation and growth of states in both lowlands and highlands may have been fostered by continuous interchange between the coast and interior (mann, ) . moreover the climate strongly linked the lowlands to the highlands. for example, strong el niño events in peru are manifested as teleconnections, for example flooding on the north coast coincident with drought in the southern highlands (moseley, ) . the moche civilization existed at the mercy of droughts, earthquakes, and floods (fagan, ) . it seems that a period of collapse in the valleys, known as the moche iv-v transition, occurred rather abruptly at around ad . the main irrigation channels became covered by sand dunes at the time of abandonment (de menocal, ; moseley et al., ) . the subsequent moche v culture was re-established inland between ad and , near the confluence of highland rivers draining the andean foothills where the water supply was more reliable (de menocal, ) . for earlier periods in the same region, successive earthquakes, el-niño flooding, beach ridge formation nourished by sediment eroded during earthquakes and floods, and sand dune incursion caused a series of natural disasters that contributed to the demise of local coastal settlements (keefer et al., ; sandweiss et al., ) . the collapse of the moche coincided with a megadrought, followed by large el-niño floods, which have been inferred from a study of the annually layered ice cored in the quelccaya ice cap in the cordillera occidental of the southern peruvian highlands (thompson, ) . this area lies in the same zone of seasonal rainfall as the mountains above the moche country. the accumulation rate of ice shows a dry period from ad to , followed by a wet period between ad and . during the three-decade drought, the moche capital was moved inland and northward and people settled at valley necks, where they could have better control on water resources (shimada et al., ) . the data strongly suggest that highland cultures flourished when the mountains were wetter than normal and that coastal cultures flourished when the mountains were drier than normal (de menocal, ) . drought and the moche leaders' inability to alleviate it led to unrest and fighting among communities. the strife, together with limited food and productive agricultural land, led to a slow deterioration and, ultimately, to the destruction of the moche civilization in the following centuries (dillehay et al., ) . the decline was presaged by an earlier -year-long drought that began in ad . in summary, the moche iv-v transition and the shift of their activities from the coast to the highlands resulted from stresses caused by a succession of natural disasters (moseley et al., ) . the maya indian civilization flourished in central america ( fig. ) from ad to , with roots in the preceding millennia (wahl et al., ) . the empire collapsed around ad at the heyday of its intellectual and cultural development. the maya had by then developed a sophisticated hierarchical society with a writing system and astronomical knowledge. they left behind impressive cities dominated by large temples. they, however, lived in a fragile ecosystem that ranged from tropical forest in guatemala and southeastern yucatan to desert in northwestern yucatan. their agriculture was based on slash-and-burn practices, terraced hill slopes, drained fields and irrigation channels. the farmers had many means of intensifying agriculture. however, a relatively large numbers of workers depended on others for food production. productivity was low and a maya peasant could produce only twice the needs of himself and his family (diamond, ) . this type of agriculture caused significant erosion. today many lakes, canals and reservoirs (fig. ) contain what is called the "maya clay," a thick inorganic layer that started to form after about years ago (brenner et al., ) . the deposit reflects severe soil erosion that resulted from widespread, human-mediated deforestation. erosion decreased progressively towards the late classic period due to soil conservation measures (beach et al., ) . the end of this deposition corresponds to the maya collapse and natural reforestation of the landscape (brenner et al., ) . when drought became more common near the end of the first millennium ad, the maya attempted to adapt to the changing environment through spiritual means. they built more temples and held more ceremonies. warfare became chronic, and limited food supply made it impossible for any maya principality to maintain control over the whole region (diamond, ) . population decreased in the late ninth century due to a combination of natural factors, such as erosion and drought, and social ones such as overpopulation, social upheaval, and warfare. no buildings show glyphs with dates after ad , although some construction continued (diamond, ; douglas et al., ) . lake sediments in yucatán provided the first evidence that climatic change may have been implicated in this decline. sediments recovered from closed lake basins reveal the onset of much drier conditions between ad and (hodell et al., ) . oxygen isotope data from cores collected at lake punta laguna, in the yucatán lowlands, show a period of higher evaporation from ad to (curtis et al., ) . the peak in @ o, representing the highest evaporation, is at ad , which coincides with the maya hiatus, an early/late classic boundary in mayan culture. another @ o peak at ad concurs with the time of the collapse of the classic maya civilization between ad and . a third peak at ad may correlate with postclassical abandonment of sites on the northern yucatán peninsula (curtis et al., ) . other lake records have since confirmed this period of greater aridity, with peak periods of droughts at times of major mayan cultural change (e.g., lake salpetén in the petén lowland in northern guatemala; anselmetti et al., ; douglas et al., ) . other proxies corroborating changes in erosion and agriculture, respectively, are sediment accumulation rates and agricultural indicators in pollen assemblages, such as the pollen of corn or zea mays (wahl et al., ) . varved sediments in a core taken in the cariaco basin, off venezuela, have yielded similar high-resolution records. a major drought lasting years has been identified at the time of the collapse of the classic maya civilization (haug et al., ) . the cause of this drought is thought to be a southward displacement of the intertropical convergence zone. likewise, recent work on the greater antilles has shown a period of droughts and societal change (lane et al., ) . however in this case, it led to intensified agricultural practices and population increase. the norse people who lived in greenland ( fig. ) between about ad and were not one ethnic group, but rather a spectrum of peoples with many different languages. the main groups, however, were norwegians and danes. they arrived from iceland, which they had colonized in ad . the causes for moving to greenland are diverse: ideology, climatic change, overpopulation, scarcity of land and floods, technological development, and internal political conflict (diamond, ) . they arrived on cargo ships, the knorrs, using prevailing currents in the ice-free waters of the north atlantic. they found in greenland an uninhabited, virgin landscape, because the inuit of the thule tradition only came later. the norse soon established a herding economy supported by hunting and, initially, barley. at its peak, the norse population was about , with about farms, churches, a cathedral, and a monastery. the economy, however, depended on trade with the homelands. in exchange for whale, walrus and seal skins, whale bones and ivory, they received silver, gold, silk, spices, salt, and wheat. after about ad , the settlers started trading also with the inuit, who were very well adapted to this harsh environment. the inuit used skin kayaks for ocean hunting, sledges, recurved bow with a sinew backing, and the toggle harpoon to hunt through ice year round. they also produced skin clothes. the norse life was precarious, as they relied on a short summer season to produce much of what they needed for the winter, for example hay (barlow et al., ) . they especially feared the exhaustion of stored meat and dairy products before the beginnings of spring sealing. a study of insects found in the floor layers inside collapsed houses has provided information on the final days of the norse settlements (panagiotakopulu et al., ) . the fly fauna in one of the excavated farms changes from species requiring warmth indicating fire in the hearth, to cold-adapted species indicating a lack of burning wood and finally to outdoor species caused by roof collapse. these changes are accompanied by a change from insects that thrive in a relatively clean environment, although one with human parasites such as fleas and lice, to one rich in carrion. it appears from a study of bones in kitchen middens that, in the final years, the norse were reduced to eating their dogs, even though they were essential for hunting (panagiotakopulu et al., ) . greenland ice cores show that climate cooled slowly from ad to a low at about ad (dahl-jensen et al., ) . stock rearing became unreliable toward the end of this period; crops failed often; and the settlements were cut off from the outside world by sea ice for several years at a time. unlike the inuit, the norse settlers were unable to adapt to living off the sea, where fish and seals remained plentiful year round, even as climate changed. the last recorded contact was in ad , although archaeological evidence suggests that one settlement persisted until about ad . the crew of a ship that visited the norse settlement in ad noted only abandoned farms. another factor that contributed to the decline of the settlements is erosion. when the norse arrived, they found a sparse arctic scrub of dwarf birches, willows, heathers, and junipers, which they cleared for agriculture. land clearing, together with grazing, destroyed the soil and limited the economic activities of the norse (edwards et al., ) . diamond ( ) attributes the end of the norse settlements to a combination of five factors: the little ice age reduction in temperatures and increase in sea ice; damage to the environment by overgrazing and land clearance for agriculture; conflict with the inuit; reduction of trade with iceland and europe; and the unwillingness of the norse to learn from the inuit who were considered inferior (mcgovern, ) . polynesians came from melanesia (fig. ) only within the past years at most (hurles et al., ) . maoris arrived in new zealand years ago, and other polynesians reached easter island only about years ago (hunt and lipo, ) . early human activity is easier to identify in remote oceania than in the rest of the world, because of the relatively short time of human occupation. moreover, biodiversity decreases eastward across the pacific; thus human disturbances are more obvious and identifiable on remote islands far from continents. human-associated activities such as burning, hunting, and the introduction of new species are apparent in the archaeological record (hurles et al., ) . the settlers were farmers, who used slash-and-burn methods to clear land. they rapidly destroyed the natural subtropical forests. moreover, they brought rats that suppressed coastal and lowland plants and a variety of animals (towns et al., ) . archaeological sites commonly contain seeds with traces of rat gnawing (prebble and wilmshurst, ) . the recent human colonization of easter, necker and nihoa islands led to massive deforestation and extensive modification of the landscape (rolett and diamond, ) . in the case of easter island, a nearly total destruction of its forest caused the progressive or sudden collapse of a primitive society (cañellas-boltà et al., ) . the collapse coincided with the building of impressive statues to gods who, the residents hoped, would bring a solution to their problems (rolett and diamond, ; diamond, ) . in new zealand, the arrival of europeans in the mid- th century brought renewed deforestation, this time with far stronger erosion, than had occurred during the maori occupation. europeans settled not only the flat plains but also the steep slopes (mcglone, ) , and, more importantly, they introduced millions of sheep that further reduced plant cover. these activities eroded slopes and triggered large landslides (mcglone, ; glade, ) . page and trustrum ( ) studied sediment cores from several new zealand lakes and reported an increase in erosion associated with the arrival of the polynesians, followed by a further, even more dramatic, increase with the arrival of europeans. a similar close relation between forest cover, soil erosion, and the two fluxes of immigrant populations has been noted for the cook islands (kirch, ) . no catastrophes leading to the collapse of a civilization have occurred in the past several centuries. nevertheless, the number of disasters is increasing. today, natural hazards affect a larger number of people, due to population growth and increased settlement of risky environments. the laki eruption (iceland; fig. ) in ad - produced the largest lava flow in recorded history. during the -month-long eruption, a -km-long fissure formed, and huge amounts of sulfur dioxide were released into the atmosphere (jacoby et al., ; thordarson and self, ) . sulfuric acid and volatiles emitted by the eruption damaged vegetation from the arctic ocean to the mediterranean region (grattan, ) . poor weather, acid rain, and fog in iceland led to the death of up to a quarter of the population and three-quarters of the livestock (grattan, ) . the eruption also cooled climate in europe and the middle east for - years (stothers, ) . europe was affected by a dry fog for months; and the fog reached as far as china, northern north america, and brazil (trigo et al., ) . air pollution was so bad that human health was affected: the death rate increased dramatically in both england and france (grattan et al., ; grattan, ) . oman et al. ( ) reconstructed lower low nile floods and suggested that lower rainfalls on the nile headwaters was caused by cooling of the atmosphere that led to a strong weakening of the african and indian monsoon circulations. the fog in france came at a time of famine that possibly was exacerbated by other meteorological factors (thordarson and self, ) . some researchers have seen these events as contributors to social strife that led to the french revolution in ad (grove, ) . grattan et al. ( ) emphasize that populations that suffered most were already fragile before the eruption due to other factors, for example overpopulation in japan and the failed monsoon in india. jacoby et al. ( ) inferred the impact of the laki eruption by studying ring patterns of white spruce (picea glauca) in northern alaska (fig. ) . the maximum latewood density of boreal conifer rings differs from year to year, mainly as a function of summer temperatures. jacoby et al. ( ) found anomalously low maximum-latewood densities for ad , the lowest for a period of over years. they reconstructed a lowering of may-august mean temperatures of more than a c from the mean. the cooling was spatially variable, interior and northern alaska being one of the regions most severely affected. an analysis of the written and oral history of alaska (jacoby et al., ) indicates that the cooling caused famine among the inuit population. the diaries of russian and european explorers in the region speak of deserted villages and a notable decline in the native population (jacoby et al., ) . the impacts of the eruption were also recorded in oral traditions of a normal spring and early summer that turned suddenly frigid, snowy, and barren. a book written by william oquilluk provides a record of the oral history of his people, the kauwerak from northwest alaska. the book describes several great disasters, each one causing the death of most of the people living in northwest alaska. one of them was a very cold summer that caused the death of all but a few people in widely scattered communities on the mainland coast; this event is called "the time summer time did not come" (jacoby et al., ) . before august , krakatau was a volcanic island between sumatra and java in indonesia (fig. ) . a cataclysmic eruption that day destroyed most of the island (whittaker et al., ) and triggered a tsunami that killed more than , people (dörries, ) . giant sea waves reached the height of up to m (fig. ) and propagated through the indian ocean and the south atlantic ocean. the explosion was heard as far away as australia and india, and threw so much ash and gas into the atmosphere that it cooled temperature around the world for years. krakatau's ash led to stunning sunsets in europe and the united states that captivated artists. of the volcanic island itself, only fragments were left surrounding a large underwater caldera. in ad , a new smaller volcanic cone, anak krakatau, emerged from its center. winchester ( ) has suggested that the eruption of krakatau sparked a revolution. in ad , no sound scientific explanations were available for this disaster, thus people turned to religion for an answer, especially so in indonesia. the muslim prelates of java concluded that the eruption was punishment from god for the evil acts of men and women (winchester, ) . allah was irritated because so many people were passively allowing themselves to be ruled by the white infidels, the dutch. to appease allah, the mullahs declared the dutch had to be killed and their influence expunged. this exhortation culminated, years later, in an organized rebellion, i.e., the banten peasant's revolt in ad that killed dozens of dutch and hundreds of indonesians (winchester, ) . kartodirdjo ( ) attributed the banten peasants' revolt to cumulative factors, including a cattle plague in , an epidemic in , the krakatau eruption in , and years of famine following the eruption. volcanic eruptions, especially combined with other disasters, can be catalysts of social change. they provide a "clean break" from which to start anew (dove, ) . the province of aceh is one of the closest places to the epicenter of the giant sumatra earthquake in . the earthquake triggered a tsunami that devastated much of the west coast of the island of sumatra, including part of the capital of aceh, banda aceh (fig. ) . about , people in countries were killed in the disaster. in indonesia , were left homeless; about , of the deaths were in aceh (hyndmann, ) . the coastal geomorphology of aceh was profoundly modified by the earthquake and the tsunami (paris et al., ) . in the area of lhok nga, west of bandah aceh, the erosional imprint extended m on shore and km along riverbeds. beaches lost an average of about m m − of sediment and locally more m m − ; however, more than % of the sediments deposited inland came from offshore. a year after the tsunami, geomorphic processes were still active. comparisons of satellite photos before the tsunami, just after it, and up to years later indicate that the recovery of the beaches along the aceh coast occurs generally within years (liew et al., ) . aceh has substantial natural resources, including oil and gas (world bank, , . islam may have been introduced to southeast asia from saudi arabia through aceh. the province is religiously conservative relative to the rest of the country, which was settled by less conservative muslims from india. aceh has a history of struggle and resistance to control by outsiders, including the former dutch colonists and the indonesian government. in ad , the indonesian government gave aceh a "special territory" status, i.e., a territory that has more autonomy than most other regions of indonesia. for example, the aceh regional government has the power to construct a legal system independent of that of the national government. in spite of these concessions, a rebellion began in aceh in , resurfaced in , and gained strength in , the rebel group, the free aceh movement (gam), began an offensive and a state of emergency was proclaimed in the province (world bank, bank, , . the province was at war when the earthquake and tsunami occurred in . the local population thought that the tsunami was punishment for insufficient piety. as a consequence, religion gained even more importance after the tsunami, reflected in part in further implementation of sharia law (world bank, bank, , . the tsunami drew a lot of international attention to the conflict, wiped out many supplies, and killed many persons from both sides of the conflict. fortunately the earthquake and tsunami helped indonesia and the gam to reach a peace agreement that was signed by both parties in august (hyndmann, ) . earlier efforts to reach an agreement had failed, but the tsunami and other factors brought peace. under the agreement, aceh received further autonomy and government troops were withdrawn from the province in exchange for gam's disarmament. former gam members were freely elected to provincial and many district administrative bodies. this outcome is remarkable and inspiring given that only a few years earlier, the region was at war and cut off from the outside world (world bank, bank, , . beardsley and mcquinn ( ) compared the failure of the rebel movement in sri lanka (the liberation tigers of tamil eelam or ltte) and the contemporaneous relative success of the gam in indonesia, both of which were regions severely impacted by the tsunami. they showed that the difference probably was due to the greater need for the gam to receive support from the local population and therefore a greater desire to reach peace. on the contrary, the ltte was more dependent on the tamil diaspora and external resource support and was therefore less amenable to compromise. new orleans, louisiana, located on the delta of the mississippi river (fig. ) , was founded around ad on a riverbank levee. already from its beginnings, it was subjected to flooding and hurricanes (turner, ) . the area of new orleans is subsiding at a current rate of about mm year − . the geological setting, subsidence, and a variety of human activities are responsible for a spatially complex geomorphic landscape that was impacted by hurricane katrina in . this landscape resulted from holocene sea level rise, lateral changes in depositional environments, development of mississippi river delta lobes, and the distributary channels associated with delta development (dunbar and britsch, ) . in august , hurricane katrina made landfall as a category hurricane between two of the largest cities on the united states. gulf, new orleans to the west and mobile (alabama) to the east. it packed winds up to km h − , a storm surge up to . m high, and rainfall of up to mm. hurricane katrina was one of the most catastrophic hurricanes in united states history; nearly people were killed or went missing, and hundreds of thousands of families were affected (leroy et al., ) . much of the devastation was caused by breaches of new orleans levees and floodwalls, which left about % of the city under several meters of water. storms and hurricanes affect coastlines in a dynamic and complex way (cahoon, ) , with often large areas of land area loss. however, in a study of two subsiding marshlands along in the mississippi river delta, it has been shown that hurricanes katrina and rita introduced sediment and facilitated vegetation recovery (seed and propagule dispersion), thus counteracting sediment loss (mckee and cherry, ) . the flooding of new orleans mainly affected the low-income afro-american population. the loss of houses, reduced employment, and the rising cost of insurance made it impossible for families to return after the disaster. according to a report from the greater new orleans community data center, of new orleans neighborhoods that were flooded during hurricane katrina have less than half the households that were present in june . among these permanently displaced families are musicians, artists, and other groups representing the last vestige of louisiana's cajun/creole french heritage (leroy et al., ) . the failure of many displaced citizens to return to new orleans poses new problems for the future of the city (falk et al., ) . it was a local black population that, in the past, provided much of the semiskilled labor for new orleans' heavily service-driven labor market. questions have arisen as to who will perform the countless menial, but necessary, tasks that are the foundation of a service-based economy. one possibility is that people in southern louisiana and nearby western mississippi whose lives were disrupted by katrina will migrate to new orleans in search of employment opportunities. more likely, hispanics will move from texas to louisiana to help with the rebuilding effort, adding a new ethnoracial element to the historically diverse city. falk et al. ( ) have forecasted that the city will be smaller, more white and hispanic, more affluent, and with an economy based more on tourism and entertainment than was the case prior to hurricane katrina (falk et al., ) . an earlier series of hurricanes in neighboring texas, beginning with the "great storm" of ad , caused the economic decline of galveston and the rise of houston. the latter city is in a more sheltered position inland of the barrier island where galveston is situated (leroy et al., ) . category landfalling hurricane harvey caused in august unprecedented flooding and damage in texas. it poured more than mm of precipitation across the heavily populated houston area (zhang et al., ) . this seems to have been exacerbated by the fast runoff and poor infiltration of the town as well as by the mesoscale convective systems typical of built areas. a study of sediment transport and bathymetry on coastal bays south of houston at port aransas indicates a significant seaward displacement of sand with removal from barrier islands and deposition on the inner shelf (goff et al., ) . this is contrary to the usual concept of storm-driven, landward migration of barrier islands through wave-driven erosion of the shoreface and wash-over deposition on the bay (goff et al., ) . four factors, i.e., time, space, people, and type of hazards, combine in a variety of ways to cause a disaster or even a catastrophe (fig. ; leroy, ; leroy et al., ) . the first factor is the speed of onset and duration of the event. preparation is not possible for a rapid-onset event. a destructive event that lasts several days, for example a flood, quickly exhausts emergency food and water supplies. the second factor is the size of area affected or the proportion of settlement affected. people will not hesitate to move away when no other possibility turns up. in many cases, however, the affected area is so large that there is nowhere to go. the third factor is the type of society that is impacted. a society may be very adaptable, mobile (e.g., nomads), or rigid with a strong hierarchy or a strong attachment to some geographical features. this is what diamond ( ) calls dropping core societal values. for example, moving new orleans farther up the mississippi river would appear to be scientifically sound, but federal and state authorities will not suggest a move, because the present location of the city is perceived to be good for economic reasons, for example a harbor that supports the oil industry. a lack of flexibility is well illustrated by the norse in greenland. they chose not to change their way of life and refused to learn from the inuit. the fourth factor is the type of hazard and its recurrence and the accumulation of diverse types of hazards. repeated hurricanes like hurricane katrina followed by hurricane rita will test the resilience of a society. in other cases, successive hazards of different types will have the same cumulative impact, described as a ratchet effect by chambers ( ) and ford et al. ( ) . the moche collapse illustrates this point because it appeared to be caused, in part, by a succession of droughts, floods, and earthquakes. in the devastating earthquake that struck port-au-prince, the capital of haiti, closely followed the disasters caused by hurricanes gustave and ike in , leaving the country with very little coping capacity. moreover, in this case, the disasters affected a poor country with weak institutions. during the earthquake, government officials essential for the organization of the rescue operation were killed. moreover, aid workers caused a deadly cholera epidemic, bringing the death count from , to , people. a catastrophe tends to develop when many of the negative aspects of the four factors coincide. disaster fig. the four actors leading to disasters and catastrophes. environmental changes commonly are associated with geomorphic changes, which may negatively impact people because adaptation is expensive and time-consuming. changes have clearly led to various types of dark ages in archaeology. examples of negative impacts of environmental changes include the aridification at the end of the eastern roman empire (issar and zohar, ) and the global dust veil of ad that resulted from a comet impact or a cluster of large volcanic eruptions (baillie, (baillie, , büntgen et al., ) . environmental change, however, can also have positive impacts that improve the human condition and increase societal complexity. brooks ( ) has argued that the earliest complex, highly organized, state-level societies emerged throughout the global monsoon belt caused by an orbitally-driven decrease of insolation leading to an increasing aridity. one of his examples is the aridification of the sahara (shrinking of large lakes at the end of the ahp) and development of the pharaonic civilizations. the seemingly deleterious environmental effects of the younger dryas (aridification of the middle east) led to an important innovation that facilitated the subsequent development of civilization, i.e., the domestication of cereals (brooks, ) . rapid landscape changes seem to create conditions from which innovation may emerge. the argument that technological sophistication protects modern society from natural disasters is a grave misconception. our modern technological world remains fragile and vulnerable to disasters. this is well illustrated by covid- that caused a worldwide lockdown in to limit disease propagation and loss of life. this pandemic had long-term economic impacts. modern medicine remained powerless for months on. technology has created a global interconnectedness; metaphorically we are now one island. our interdependence is illustrated by the fact that, of the five largest power failures in the world in terms of number of people affected (anonymous, ) , four have resulted from the cascading effects of localized outages due to poor weather in a rather small area: southern brazil in (> million people affected) due to a lightning strike; brazil-paraguay in ( million people) due to heavy rain and strong winds; italy and southern switzerland in ( million people) due to storms; in northeastern united states and southeastern canada in (> million people) due to a hot day. although those power outages lasted only a few hours, the outage caused by the north american ice storm of left some areas without power for several weeks and millions of trees were damaged or fell from the heavy ice. if such events happened during a period of political upheaval or war, or in combination with another disaster such as an earthquake, power could not be restored so quickly. another illustration of our interconnection is our reliance on meteorological satellites. the satellite network could be disrupted by a large volcanic eruption or an unprecedented magnetic storm. data provided by satellites are critical for daily weather forecasts, and any disruption in the network would reduce the accuracy of forecasts, especially in the southern hemisphere where fewer ground-based observations are available. the mount pinatubo eruption in the philippines in june decreased the quality of the satellite-derived sea surface temperature measurements. negative biases of > c for august and september was observed in the tropics, sufficient to mask an el-niño event that was unfolding (reynolds, ) . another aspect of interconnectedness that is of concern is global food supplies. in order to understand the impact of a global natural hazard such as cometary impact or supereruptions and the ensuing cooling of the weather, the analogy of a nuclear war can be used. such a model shows its impact on weather and food production, especially grain (rampino, ) . it is chilling to note that global food reserves are extremely low. estimates range from slightly less than days and falling (helfand, ) to days (laio et al., ) . any global hazards would immediately lead to a global famine. many countries suffer famine even when surpluses exist in nearby countries. problems of food distribution and differences in wealth hinder relief. guatemala is a country exporting food, yet half of the children suffer from chronic undernutrition (loewenberg, ) . because of population growth, increasingly marginal or hazardous environments become inhabited, for example the flanks of volcanoes (chester et al., ) , landslide-prone areas (e.g., in the caucasus; gracheva and golyeva, ) , floodplains (e.g., the ganges-brahmaputra delta), low-lying or even subsiding coasts (new orleans and parts of the netherlands), and areas of uncertain rainfall (sahel). the concept of "climatic refugee" is a fairly new one, but may soon apply to large numbers of people. refugees move to two types of places. firstly, they may move to unoccupied or sparsely populated environments with fragile ecosystems. for example, people are settling natural areas near the great lakes in eastern africa; these areas are being rapidly deforested causing erosion and ecological damage. secondly, refugees may migrate to cities. for instance, migrants concentrate in the megacity of dhaka, which is itself in danger, as it is only m above sea level, in the path of cyclone, and has no infrastructure to accommodate more poor people. warning systems are one strategy for reducing risk from natural hazards. a complete and effective warning system comprises four inter-related elements: knowledge of hazards and vulnerability, monitoring and warning services, communication, and the capacity to respond (un escap, ). tsunami warning systems were installed in the indian ocean after the tsunami. they range from beach sirens to deep-ocean monitoring systems. the government of indonesia provides information and training courses for evacuation in the event of a tsunami (fig. ) . the september tsunami in sumatra illustrated the progress that has been made, but also highlighted remaining weaknesses (un escap, ) . no warning was issued during the eruption of the anak krakatau and people were taken by surprise, leading to much loss of life (syamsidik et al., ) . understanding natural hazards, disasters, and human responses to them requires a multidisciplinary approach, involving both physical and social sciences. this approach is supported by an increasing number of collaborative and conference programs funded by international organizations such as unesco, the international union of geological sciences (iugs), and the international union for quaternary research (inqua). communication of science is increasingly being recognized as an important part of student training at the university level. iugs and the geological survey of canada, for example, have programs to sensitize earth scientists to the importance of communicating geosciences, with a strong emphasis on the role of rapid landscape changes (liverman, ) . populations, however, may be reticent to learn from scientists, because they may be perceived as distant advisers unaware of the local situation. an example of the successful transfer of relevant geosciences information is the case of the recent rise of many lakes in the argentine pampas. the geologist involved in a study of the problem came from the affected community, mar chiquita, and was able to establish a sense of trust with the residents that facilitated the transfer of knowledge and led to successful mitigation measures (leroy et al., ) . natural parks or limited-use zones should be created in areas of repeated natural disasters (leroy, ) . for example rothaus et al. ( ) has suggested strict rebuilding guidelines and limitations on land use in the area struck by the izmit-düzce earthquake in northwest turkey, instead of the usual rebuilding programs. governments today are unable to move people away from dangerous areas. unemployment and increased insurance premiums are the two modern forces in the western world that can provide impetus for people to relocate. adaptation and mitigation are key to survival, but they should not involve recovery to the same levels that existed before a disaster occurred. rather, adaptation and mitigation should take society to a higher level based on lessons learned from the disaster (leroy, ) . pressure arises after a disaster to rapidly rebuild and usually in the same place. it may be better to reconstruct elsewhere. with rapid sea-level rise such as the th century cases of the caspian sea and the pampean lakes in argentina (leroy et al., ) or faced with the danger of tsunami such as in sri lanka after the tsunami, it is tempting to prevent building along coasts. this strategy, however, is not feasible because of the economic and societal values of the coastal zone. moreover land ownership and space availability are often additional problems. in iran along the caspian coast, the government finds that, in practice, it can only have limited influence, mostly on state constructions and large hotels (leroy et al., ) . the evolution of societies is inscribed in geomorphology: either societies change in response to changing landscapes; or landscapes evolve under human pressure. humans and nature have never been more closely inter-related, although more than half the world population now lives in cities seemingly disconnected from nature. increasingly humans tend to forget that the earth does not belong to them, rather they belong to the earth. disasters and catastrophes typically have an element of surprise. it is impossible to forecast all possible disaster scenarios, thus surprises are unavoidable. whatever technology and education are applied to preparedness, a disaster will rarely be properly forecast and mitigation will never be satisfactory. four factors are involved in a disaster, i.e., time, space, society, and the type of events. recurrence of events causing the ratchet effect and the succession of different hazards in an area can limit long-term recovery and, in extreme cases, lead to societal collapse. the relationships among hazard, disaster, and political and social change are not always clear. hazards must be seen in the context of many other factors when considering the cause of a disaster such as hurricane katrina. considering the many problems that will arise from global warming or population growth, one could argue that a major catastrophe is in the offing. adaptation is the key to the survival of our civilization as our natural world is in constant flux. we have seen in this article that catastrophes have changed our world, both negatively and positively. what will be the future? wally was right: predictive ability of the north atlantic "conveyor belt" hypothesis for abrupt climate change list of power outages quantification of soil erosion rates related to ancient maya deforestation exodus to arthur proposed re-dating of the european ice core chronology by seven years prior to the th century ad interdisciplinary investigations of the end of norse western settlement in greenland geoarchaeology and geomorphology: soils, sediments, and societies (a special issue of geomorphology) a review of human and natural changes in maya lowland wetlands over the holocene rebel groups as predatory organizations, the political effects of the tsunami in indonesia and sri lanka a revised chronology for the adoption of agriculture in the southern levant and the role of lateglacial climatic change an abrupt wind shift in western europe at the onset of the younger dryas cold period cultural responses to aridity in the middle holocene and increased social complexity the climate-environment-society nexus in the sahara from prehistoric times to the present day cooling and societal change during the late antique little ice age from to around ad a review of major storm impacts on coastal wetland elevations vegetation changes and human settlement of easter island during the last millennia: a multiproxy study of the lake raraku sediments chambers r ( ) vulnerability, coping and policy recent advances in moche archaeology the increasing exposure of cities to the effects of volcanic eruptions: a global survey paleohydraulics of the last outburst flood from glacial lake agassiz and the bp cold event climate variability on the yucatan peninsula (mexico) during the past years, and implications for maya cultural evolution past temperatures directly from the greenland ice sheet cultural responses to climate change during the late holocene abrupt onset and termination of the african humid period: rapid climate responses to gradual insolation forcing pre-industrial human and environment interactions in northern peru during the late holocene global science: the eruption of krakatau drought, agricultural adaptation, and socio-political collapse in the maya lowlands impacts of climate change on the collapse of lowland maya civilization perception of volcanic eruption as agent of change on merapi volcano, central java geology of the new orleans area and the canal levee failures high-resolution paleoenvironmental and chronological investigations of norse landnám at tasiusaq, eastern settlement floods, famines and emperors the long summer hurricane katrina and new orleanians' sense of place, return and reconstitution or vulnerability to climate change in the arctic: a case study from arctic bay contrasting patterns in crop domestication and domestication rates: recent archaeobotanical insights from the old world environmental change and cultural response around cal. yr bp in the yishu river basin landslide occurrence as a response to land use change: a review of evidence from new zealand an outflow on the left side of hurricane harvey: erosion of barrier sand and seaward transport through landslides in mountain regions: hazards, resources and information pollution and paradigms: lessons from icelandic volcanism for continental flood basalt studies aspects of armageddon: an exploration of the role of volcanic eruptions in human history and civilization volcanic air pollution and mortality in france - the long shadow: understanding the influence of the laki fissure eruption on human mortality in europe the great el niño of - and its global consequences: reconstructing an extreme climate event in world environmental history holocene lakes and prehistoric settlements of the western faiyum third millennium bc climate change and old world collapse climate and the collapse of maya civilization an assessment of the extent of projected global famine resulting from limited, regional nuclear war possible role of climate in the collapse of classic maya civilization environmental change and archaeology: lake evolution and human occupation in the eastern sahara during the holocene late colonization of easter island untangling oceanic settlement: the edge of the knowable siting conflict and peace in post-tsunami sri lanka and aceh climate change-environment and civilization in the middle east laki eruption of , tree rings, and disaster for northwest alaska inuit the peasants' revolt of banten in : its conditions, course and sequel. verhandelingen van het koninklijk instituut voor taal-, land-en volkenkunde a -year record of floods and debris flows in the ilo region of southern peru and its relation to el niño events and great earthquakes late holocene human-induced modifications to a central polynesian island ecosystem climate-controlled holocene occupation in the sahara: motor of africa's evolution the past and future of food stocks beyond the mayan lowlands: impacts of the terminal classic drought in the caribbean antilles understanding one's place in the watershed: how earth science can inform perceptions about the future of the new orleans region from natural hazard to environmental catastrophe, past and present the role of geosciences in the improvement of mitigation of natural disasters: five case studies recovery from a large tsunami mapped over time: the aceh coast communicating geological hazards: educating, training and assisting geoscientists in communication skills guatemala 's malnutrition crisis oldest civilization in the americas revealed the polynesian settlement of new zealand in relation to environmental and biotic changes climate, correlation, and causation in norse greenland hurricane katrina sediment slowed elevation loss in subsiding brackish marshes of the mississippi river delta the younger dryas episode and the radiocarbon chronologies of the lake huleh and ghab valley pollen diagrams western canadian glaciers advance in concert with climate change circa . ka did farming arise from a misapplication of social intelligence? punctuated equilibrium: searching the ancient record for el niño convergent catastrophe and the demise of dos cabezas high-latitude eruptions cast shadow over the african monsoon and the flow of the nile a late holocene lake sediment record of the erosion response to land use in a steepland catchment fossil insect evidence for the end of the western settlement in norse greenland christopher tsunamis as geomorphic crises: lessons from the december , tsunami in lhok nga sahara, sous les sables . . . des lacs detecting the initial impact of humans and introduced species on island environments in remote oceania using palaeoecology the nature of selection during plant domestication supereruptions as a threat to civilizations on earth-like planets simulation of the holocene climate evolution in northern africa: the termination of the african humid period impact of mount pinatubo aerosols on satellite-derived sea surface temperatures environmental predictors of pre-european deforestation on pacific islands regional considerations of coastline change, tsunami damage and recovery along the southern coast of the bay of izmit (the kocaeli (turkey) earthquake of plows, plagues and petroleum: how humans took control of climate status of the black sea flood hypothesis noah's flood: the new scientific discoveries about the event that changed history an abrupt drowning of the black sea shelf environmental change and economic development in coastal peru between , and , years ago cultural impacts of severe droughts in the prehistoric andes: application of a , -year ice core precipitation record nile flow failure at the end of the old kingdom, egypt: strontium isotopic and petrologic evidence holocene climate and cultural evolution in late prehistoric-early historic west asia high-resolution greenland ice core data show abrupt climate change happens in few years volcanic dry fogs, climate cooling, and plague pandemics in europe and the middle east the december mount anak krakatau volcanogenic tsunami on sunda strait coasts, indonesia: tsunami and damage characteristics reconstructing the paleo enso records from tropical and subtropical ice cores atmospheric and environmental effects of the - laki eruption: a review and reassessment have the harmful effects of introduced rats on islands been exaggerated? witnessing the impact of the - laki eruption in the southern hemisphere geomorphology, geography, and the new orleans after iberville and bienville catastrophic early holocene sea level rise, human migration and the neolithic transition in europe tsunami early warning systems in the indian ocean and southeast asia holocene vegetation change in the northern peten and its implications for maya prehistory what drives societal collapse? plant recolonization and vegetation succession on the krakatau islands late pleistocene and early holocene climate and the beginnings of cultivation in northern syria krakatau: the day the world exploded multi-stakeholder review of post-conflict programming in aceh: identifying the foundations for sustainable peace and development in aceh indonesia: a reconstruction chapter ends eight years after the tsunami lateglacial and early-holocene dry climates from the balkan peninsula to southern siberia controversy over the great flood hypotheses in the black sea in light of geological, paleontological, and archaeological evidence urbanization exacerbated the rainfall and flooding caused by hurricane harvey in houston acknowledgments i am grateful to prof. john clague for inviting me to contribute to this volume. i am indebted to f. baede, for providing access to literature relating to the indonesian independence and to k. arpe, m. turner, m. eglème, and r. gracheva, who commented on the first versions of this article. key: cord- -ztawznod authors: yehya, nadir; venkataramani, atheendar; harhay, michael o title: statewide interventions and covid- mortality in the united states: an observational study date: - - journal: clin infect dis doi: . /cid/ciaa sha: doc_id: cord_uid: ztawznod background: social distancing is encouraged to mitigate viral spreading during outbreaks. however, the association between distancing and patient-centered outcomes in covid- has not been demonstrated. in the united states social distancing orders are implemented at the state level with variable timing of onset. emergency declarations and school closures were two early statewide interventions. methods: to determine whether later distancing interventions were associated with higher mortality, we performed a state-level analysis in , covid- non-survivors. we tested the association between timing of emergency declarations and school closures with -day mortality using multivariable negative binomial regression. day for each state was set to when they recorded ≥ deaths. we performed sensitivity analyses to test model assumptions. results: at time of analysis, of states had ≥ deaths and follow-up days. both later emergency declaration (adjusted mortality rate ratio [amrr] . per day delay, % ci . to . , p= . ) and later school closure (amrr . , % ci . to . , p= . ) were associated with more deaths. when assessing all states and setting day to the day a state recorded its first death, delays in declaring an emergency (amrr . , % ci . to . , p= . ) or closing schools (amrr . , % ci . to . , p< . ) were associated with more deaths. results were unchanged when excluding new york and new jersey. conclusions: later statewide emergency declarations and school closure were associated with higher covid- mortality. each day of delay increased mortality risk to %. nonpharmaceutical interventions, such as social distancing and issuance of emergency public health warnings seeking to modify activity, are recommended to mitigate the spread of viral epidemics and pandemics [ ] [ ] [ ] [ ] [ ] [ ] [ ] , including the current sars-cov- and its associated covid- disease. historical analysis of the - influenza pandemic during the second wave of infections that examined cities in the united states demonstrated an association between earlier school closures and bans on public gatherings with lower mortality [ ] . a recent modeling study supported multilayered nonpharmaceutical interventions, including quarantine, school closures, and workplace distancing, for covid- [ ] . at this stage in the pandemic, the efficacy of social distancing measures on patientcentered outcomes specifically for sars-cov- and covid- have not been demonstrated. in the united states, social distancing measures have been implemented primarily at the local and state levels, with evidence of mistrust for their efficacy or necessity. as these interventions are fundamentally political and decided upon by elected officials, real-time evidence of efficacy would be helpful for informing policy. if social distancing measures were causal for improved outcomes, we reasoned there would be a dose-response, with states implementing distancing measures later experiencing worse outcomes. this rationale is premised on the association retrospectively seen between timing of social distancing measures and mortality during the - influenza pandemic [ ] . therefore, we assessed the association between the timing of emergency declarations and school closures, two specific statewide distancing measures, and subsequent covid- mortality. we hypothesized that states with delayed emergency declarations and school closures would experience higher covid- mortality. a c c e p t e d m a n u s c r i p t this was an ecologic study of publicly available data. the this was a decedent-only analysis of attributed covid- deaths in the hopkins coronavirus resource center between january , and april , (n = , non-survivors). we chose to analyze decedents given the relatively low and variable rates of testing between states [ , ] , making number of cases unreliable. we reasoned that eventual covid- non-survivors were more likely to have experienced severe infection and have undergone testing, thereby making this the most accurate of available metrics to track pandemic spread. our co-primary exposures were the number of days between a state experiencing ≥ covid- deaths (standardized across states as day ) and implementation of a statewide emergency declaration (day of emergency declaration minus day ), and separately school (kindergarten through grade ) closure (day of school closure minus day ). we chose emergency declarations and school closures as a c c e p t e d m a n u s c r i p t the primary exposures because they were unambiguous interventions. other distancing measures, such as bans on public gatherings, closure of non-essential businesses, and shelter-in-place orders were variably implemented between states, using divergent definitions, thresholds for maximum group sizes, and carve-out exemptions. the primary outcome was covid- mortality on day . we chose the timepoint of days because we reasoned that, if a statewide emergency declarations and school closures impacted mortality, then several weeks would be required to allow for a reduction in transmission, hospitalizations, and mortality. potential state-level confounders considered a priori were population, population density, percent of the population < years of age, percent ≥ years of age, percent black, percent hispanic, and percent below census-designated poverty threshold. we included the country-level confounder of census-designated division, which divides the country into nine geographic regions. all analyses were performed in stata se/ . (statacorp, college station, tx, usa) on april , (ny and mh separately). summary data are presented as mean ± standard deviation (sd) or as proportions, and analyzed for monotonic trends using a non-parametric test of trend across tertiles of states ordered based on timing of emergency declarations or school closings. for our primary analyses, we used multivariable negative binomial regression to test the association between earlier emergency to test the dependence of our results on our assumptions, we performed a secondary analysis where we set day to the day when a state recorded its first covid- death. exposures were calculated as before (day of emergency declaration or of school closures minus day ), while the primary outcome was death on april , . the negative binomial model allows for an offset to allow states to have different lengths of follow-up time. these analyses were adjusted for the same confounders as in the primary analyses. second, because deaths per million is a common method to compare localities, we provide an analysis testing the association between deaths per million at the state level after multivariable adjustment relative to timing of emergency declarations or statewide school closures. we set day to equal when a state experienced at least death per million, and followed deaths until april , , allowing different follow-up times between states. finally, to account for the potential impact from the excess of deaths in the new york city metropolitan area, all models above were re-run excluding new york and new jersey. the funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript. the corresponding author had full access to the data and had final responsibility for the decision to submit for publication. at the time of analysis on april , , of states had experienced ≥ deaths by april , , thus ensuring availability of -day mortality. these states comprised the cohort for our primary analyses (tables and ). timing of emergency declarations and school closing were highly correlated (r = . , p < . ). states declared an emergency at a median of - (interquartile range [iqr] - , - ) days relative to experiencing ≥ covid- deaths, with all states declaring an a c c e p t e d m a n u s c r i p t emergency prior to recording at least deaths. states implemented school closures at a median of - (iqr - , - ) days relative to experiencing ≥ covid- deaths, with of states ( %) closing schools before experiencing at least deaths. states declaring emergencies and closing schools earlier had a lower population, but were otherwise comparable to states closing schools later. after adjusting for confounders, later emergency declaration was associated with higher mortality ( figure a ). assigning the day that a particular state had ≥ covid- deaths as day , every day a state delayed declaring an emergency increased -day mortality by % (mrr . , % ci . to . ). when assigning day as the day a state experienced its first covid- death and using data from all states until april , ( figure b) , mortality increased by % (mrr . , % ci . to . ) for every day of delay. results were consistent when excluding new york and new jersey from both analysis ( figures c and d) , with later declaration of emergency associated with higher mortality risk. later implementation of a statewide school closure was similarly associated with higher mortality (figure a ). assigning the day that a particular state had ≥ covid- deaths as day , for every day a state delayed implementing a school closure, -day mortality risk increased by % (mrr . , % ci . to . ). when assigning day as the day that a state experienced its first covid- death and using all available data from all states until april , ( figure b) , for every day a state delayed implementing a school closure, final mortality increased by % (mrr . , % ci . to . ). results were consistent when excluding new york and new jersey from both analysis ( figures c and d ), with later implementation of school closures associated with higher mortality risk. a c c e p t e d m a n u s c r i p t when analyzing deaths per million as the primary outcome (supplementary figure ) , later implementation of emergency declarations was associated with higher mortality (mrr . , % ci . to . ), although this did not reach a traditional threshold for statistical significance (p = . ). later implementation of statewide school closure was similarly associated with higher mortality (mrr . , % ci . to . ), which attained statistical significance (p = . ). results were similar when excluding new york and new jersey (supplementary figure b and d). as different regions of the united states experienced local epidemics, we assessed the cumulative death curves for each census-designated division (supplementary figure ) . curves grew in all divisions, without evidence for plateauing. census divisions and were among the latest of the nine divisions to implement statewide emergency declarations, whereas divisions and , which showed the slowest increase in deaths, were the two earliest. states implementing emergency declarations or school closures later in the course of the pandemic experienced higher covid- mortality, with each day of delay increasing mortality risk to %. this effect size was attenuated when measured as deaths per million, but still consistent with lower mortality with earlier statewide declarations. to our knowledge, this is the first demonstration of an association between statewide social distancing orders and mortality during covid- . our results support early social distancing as a nonpharmaceutical intervention for reducing mortality. our study design and results do not directly implicate timing of either emergency declarations or school closings specifically as causal for reduced mortality, although causality is plausible. emergency a c c e p t e d m a n u s c r i p t declarations, for example, have been shown to reduce social contacts. in a time-series analysis conducted by the national bureau of economic research (nber) during the early weeks of covid- , state-level emergency declarations had the largest reduction in within-state mixing [ ] . thus, early state-level social distancing measures, including declaration of an emergency, may have contributed to reducing the spread of covid- , and by extension lower mortality. the causality of timing of school closures on covid- mortality is even less certain. while sars- cov- appears not to cause as severe a disease in children [ , ] , children are potential asymptomatic carriers. in an analysis of laboratory-confirmed cases in the united states up to april , , % of patients < years of age were completely asymptomatic, compared with % of patients to years of age [ ] . modeling of influenza and a review of nonpharmaceutical interventions for sars suggested that school closings are effective at reducing transmission between children, but only modestly affected transmission in the larger population, particularly if children were not disproportionately affected by the virus [ , ] . however, school closings also prompt additional social distancing measures as caretakers reduce their workplace presence and travel, causing indirect social distancing and improving overall population transmission rates [ ] [ ] [ ] [ ] [ ] . in the aforementioned nber time-series analysis, school closing orders had negligible impact on within-state mixing, but reduced interstate travel by % [ ] . thus, school closings may directly reduce sars-cov- transmission rates by reducing contact among asymptomatic pediatric carriers, and indirectly via changing contact patterns between adults. lastly, as this study is occurring early in covid- , it is possible that the efficacy of both emergency declarations and school closings are not in reducing total eventual covid- mortality, but in reducing peak infection rates and improving hospital surge capacity [ ]. alternatively and equally plausibly, both emergency declarations and the timing of school closures may be a proxy for the degree to which a state began to officially and unofficially implement significant social distancing [ ] . at the time of analysis, all states had declared a statewide emergency, a c c e p t e d m a n u s c r i p t with of declaring prior to their first recorded covid- death. similarly, all had closed schools, and of states had a shelter-in-place order. in all but cases, school closures preceded more restrictive shelter-in-place orders, with these orders occurring simultaneously for states. emergency declarations and school closures were among the first social distancing measures implemented in the united states. thus, our results may reflect how quickly states responded to news about the size and severity of the spreading pandemic, with emergency declarations and school closures being among the first official nonpharmaceutical interventions, rather than protective effects specific to either intervention itself. the majority of states implemented statewide school closures, and all states declared emergencies, prior to experiencing covid- deaths. hence, the time to declaring an emergency or implementing school closure relative to how we defined day could have either a positive or a negative value. earlier implementing states were likely responding to the rapid increase in cases being reported in the early hotspot states. this is consistent with data suggesting that early intervention in an exponentially growing pandemic is more efficacious than later interventions [ ] . our choice of death as an endpoint was due to concerns about inadequate and imprecise testing, thereby making counts of cases imprecise and highly variable between states. however, death is a lagging indicator, and increased time between these early interventions and eventual non-survival can result in imprecise effect estimates. reassuringly, our conclusions remained unchanged in all analyses performed. states which implemented emergency declarations and school closings later were more populous, and included the early hotspots of washington, california, and new york. it is likely that covid- had already attained a foothold in these states, and that subsequent states had the advantage of following their lead after witnessing the exponential increase in cases. this could lead to confounding in our analyses, as there were more deaths in these more populous hotspots. we attempted to control for this in three ways. first, we adjusted for state population, population density, and census-designated geographic division. next, we designated day to start at a fixed number of deaths in order to analyze m a n u s c r i p t states at the same point in the pandemic. finally, given the four-fold higher mortality in the new york city metropolitan area, we performed analyses excluding new york and new jersey. while our analysis using deaths per capita as an outcome, rathe than deaths, provided an attenuated effect size, the direction of the effect was still in favor of earlier nonpharmaceutical intervention orders. our study has limitations. both of our exposures were measured at the state level, while local school districts also closed schools of their own accord prior to state orders. however, this was estimated to only affect ~ % of the population [ ] . death rates were based on publicly available data derived from inconsistent testing using assays with imperfect test characteristics and uneven state-level reporting. thus, both exposure and outcome risk being misclassified. when reliable testing and excess mortality data are available, an analysis using those data may yield more precise estimates of the efficacy of early statewide interventions on covid- mortality. additionally, we restricted analysis to the early weeks of covid- because of concerns regarding accuracy of mortality data after may , , as covid- and social distancing continued to be politicized in the united states. indeed, multiple states started re-opening in the first weeks of may, and in some cases changed the method and timing of publicly reporting cases and deaths. due to data limitations, we were unable to adjust for potentially important confounders such as outbreaks in long-term care facilities, which may have both accelerated the spread of sars-cov- and served as an impetus for physical distancing policies. state-level variation in access to healthcare and availability of hospital and intensive care unit resources were not included, which could also bias the results. our data do not explore the association between duration of school closing orders and outcomes. however, the lesson of the - influenza pandemic is instructive: among cities investigated, no city experienced a second peak of infections while the first set of nonpharmaceutical interventions were in effect, whereas in cities which lifted initial restrictions, death rates increased [ ] . finally, ecologic studies of group-level interventions cannot apply to individuals, and we have no metrics of either state-or individual-level adherence to social distancing in this study. a c c e p t e d m a n u s c r i p t however, our study satisfies several criteria for causality between timing of early interventions and mortality, including mechanistic plausibility, prior knowledge, temporal relationship, a dose-dependent effect (earlier versus later orders), and strength and consistency of the association. these results also confirm the utility and necessity of early nonpharmaceutical intervention to reduce mortality in covid- , and may serve to increase acceptance of social distancing measures by the lay public and by policymakers. we provide evidence of an association between earlier statewide nonpharmaceutical interventions of social distancing and lower mortality in the early weeks of covid- . specifically, each day of delay in a state declaring an emergency or closing schools increased mortality risk by to %. a c c e p t e d m a n u s c r i p t a c c e p t e d m a n u s c r i p t a c c e p t e d m a n u s c r i p t a c c e p t e d m a n u s c r i p t figure strategies for containing an emerging influenza pandemic in southeast asia strategies for mitigating an influenza pandemic mitigation strategies for pandemic influenza in the united states targeted social distancing design for pandemic influenza nonpharmaceutical interventions implemented by us cities during the - influenza pandemic health outcomes and costs of community mitigation strategies for an influenza pandemic in the united states social distancing to slow the u.s. covid- epidemic: an interrupted time-series analysis interventions to mitigate early spread of sars-cov- in singapore: a modelling study an interactive web-based dashboard to track covid- in real time covid- in the usa: a question of time geographic differences in covid- cases, deaths, and incidence -united states tracking public and private responses to the covid- epidemic: evidence from state and local government actions coronavirus infection in pediatric emergency departments research g. children with covid- in pediatric emergency departments in italy sars-cov- infection in children coronavirus disease in children -united states how much would closing schools reduce transmission during an influenza pandemic? evaluation of control measures implemented in the severe acute respiratory syndrome outbreak in beijing estimating the impact of school closure on social mixing behaviour and the transmission of close contact infections in eight european countries the impact of illness and the impact of school closure on social contact patterns transmission dynamics of the influenza a (h n ) pandemic in india: the impact of holiday-related school closure a c c e p t e d m a n u s c r i p t key: cord- -p j kt authors: wiley, lindsay f title: public health law and science in the community mitigation strategy for covid- date: - - journal: j law biosci doi: . /jlb/lsaa sha: doc_id: cord_uid: p j kt in a crisis like the covid- pandemic, the role of judges is first and foremost to adjudicate urgent requests for temporary restraining orders and preliminary injunctions. this means that judges hearing challenges to bans on gatherings, orders to close gun shops, orders to halt abortion care, and detention of civil immigration detainees in crowded and unsanitary conditions are issuing orders based on the parties’ pleadings alone. there is no time—yet—for the discovery, expert testimony, or amicus briefs from professional groups that typically inform assessments of science by judges. this essay examines the role public health science is likely to play in the coming months as judges field challenges to mandatory orders adopted as part of the community mitigation the covid- pandemic. it identifies voluntary guidelines from international and federal health agencies as a resource judges rely on heavily in reviewing emergency communicable disease control orders and argues that transparency of and accountability for guidelines should therefore be held to a higher bar than their voluntary status might otherwise suggest. u n c o r r e c t e d m a n u s c r i p t the bay area orders, which broke the floodgates on mandatory sheltering-in-place as a strategy for mitigating the spread of covid- in the united states, originated in post- / public health preparedness plans and long-standing relationships between public health scientists and lawyers. the powerful combination of public health science and law has prompted more than its fair share of legal and ethical controversy. from compulsory vaccination orders to sanitary cordons, from "big gulp bans" to prohibitions on the sale of tobacco products at pharmacies, public health laws have often put judges in the position of assessing the reasonableness of restrictions on individual and economic liberty. the standards of review judges have developed to guide this task require political leaders to articulate not only the purpose of their actions but also the fit between their ends and the means they have adopted. assessing the means-ends fit usually boils down to a discussion of scientific evidence and guidelines. although the law governing public health emergency orders is surprisingly unsettled, public health law experts widely agree that an assessment of the "necessity, effectiveness, and scientific rationale" for intrusive measures is a key feature of judicial review. in a crisis like the covid- pandemic, the role of judges is first and foremost to adjudicate urgent requests for temporary restraining orders and preliminary injunctions. this means that judges hearing challenges to bans on gatherings, orders to stay at home except for essential work and needs, orders to close gun shops, orders to halt abortion care, and detention of civil immigration detainees in crowded and unsanitary conditions are issuing orders based largely on the parties" pleadings alone. there is little time-yet-for the discovery, expert testimony, or amicus briefs from professional groups that typically inform assessments of science by judges. this essay examines the role of public health scientific guidelines in the adjudication of legal challenges to mandatory orders adopted as part of the community mitigation strategy for the covid- pandemic. this examination of judicial precedents arising out of emergency communicable disease control measures-prior to and during the covid- pandemic-reveals that judges rely heavily on guidelines from the world health organization (who) and the u.s. centers for disease control (cdc). this may be cause for concern, given that federal guidelines for covid- have been slow to respond to the reality of covid- "s rapid spread and rising death toll in the us. the white house has issued guidelines independently of cdc and both sets of guidelines have fallen short of endorsing the orders mandating all residents to stay at home that the majority of states and many local governments have imposed. the essay concludes by arguing that because guidelines issued by international and federal agencies play an important role in adjudication of conflicts between emergency communicable disease control orders and civil liberties, they should be held to a higher standard of transparency and accountability than their voluntary nature might otherwise suggest. to mitigate the spread of covid- , federal, state, and local officials have exercised broad powers available to them under public health statutes and emergency declarations to close businesses and restrict the movement of individuals outside their homes. a widely cited report assumes that multi-layered non-pharmaceutical interventions, also known as community mitigation measures, will be necessary for at least three months to reduce peak impacts on health systems. while we wait for a safe and effective vaccine, some degree of community mitigation may be needed on an intermittent basis-in some places at some times-for the year or longer it takes to develop and widely distribute a safe and effective vaccine. past experience shows that community mitigation-through a combination of government supports, protections, and restrictions-is an important strategy to slow the spread of viral epidemics in addition to efforts to increase access to and the capacity of the health care system and the development and deployment of effective medical countermeasures such as vaccines and antivirals (see figure ). early evidence suggests that spread of the virus by people whose infections are not detected may play a particularly important role in covid- , potentially making more targeted containment strategies-measures to test and isolate individuals known to be infected and trace and quarantine their known contacts-insufficient in the absence of broader community mitigation measures to reduce out-of-household contacts among the general population. due to the unprecedented nature of the covid- crisis, the intrusive measures currently in force across many us jurisdictions are largely untested. benefits are anticipated based on modeling and planning exercises developed in preparation for a novel influenza pandemic, and limited studies of measures implemented in mainland china, hong kong, and parts of europe in ongoing research and surveillance are needed to assess these measures in real time. legal authority to impose restrictions on businesses, individuals, and travel may be inferred from the broad public health powers available to state governments and specific delegations of emergency powers to governors and mayors, but these measures are subject to individual rights constraints. by the end of march , lawsuits challenging gathering bans and stay at home orders were pending in the new hampshire state court system and the eastern district of new york. suits requesting injunctive relief for people in criminal custody and immigrant civil detention were pending in at least three federal jurisdictions. several suits on behalf of legal practices, firearms retailers, abortion service providers were also pending in multiple jurisdictions. more court challenges are likely to come as restrictions remain in place for weeks and months. modeling studies and cdc guidelines for pandemic influenza suggest that closing schools and other places where people gather, as every state has done to some extent in response to covid- , impedes the spread of epidemics. school closures have been deployed on a limited basis by individual districts in the us to control the spread of novel influenza viruses, with encouraging results. particularly when schools and workplaces close, it may be necessary to close other places where people would otherwise congregate. state and local restrictions on business operations under penalty of citations, fines, and loss of licenses have been ordered in nearly every us jurisdiction in response to nearly all states and many local governments have ordered bars, restaurants, theaters, gyms, shopping malls, and other settings where people tend to gather to close or limit on-site occupancy. in a majority of jurisdictions, officials have gone further, closing all non-essential businesses to the public, with specified exceptions for health-care, food and agriculture, home repair, first responders, and a few other sectors deemed essential. many have also prohibited elective medical procedures that are not time-sensitive, with a goal of promoting social distancing and preserving health care capacity. at the furthest end of the spectrum, several kylie e c ainslie, et in late april , several jurisdictions indicated that they would begin to ease restrictions on businesses, but warned that limits may need to be re-tightened in response to disease trends. even in times of low community transmission, officials indicated that restrictions on density (e.g., capping occupancy at % of what is permitted under fire safety codes) and interactions among employees and customers (e.g., limiting nonessential retail to curbside pickup) may be in place for long durations. public health authority to regulate businesses under the banner of public health is vast, but constitutional requirements of due process and equal protection of the law bar these powers from being wielded in an arbitrary or capricious manner. in addition, heightened standards of review may apply to restrictions that implicate fundamental rights, such as the right to bear arms or access family planning services. businesses affected by closures could argue that mandated closure of uncrowded, but non-essential shops where customers and employees may maintain physical distance are arbitrary and not reasonably grounded in evidence about how novel coronavirus is transmitted. though authorities could defend these bans on the ground that enforcing physical distancing requirements within each facility would be too cumbersome. the economic impacts of restrictions on businesses have already been devastating. if maintained for a long duration, the effects could be catastrophic, particularly for low-income families and small businesses. congress, federal agencies, and state and local governments have begun to implement programs to provide financial assistance, direct delivery of food and other necessities, and legal protections from eviction and utility shut-offs. yet more supportive measures will undoubtedly be needed as the crisis continues to unfold. bans on large gatherings are a cornerstone of social distancing plans developed in pandemic preparedness exercises. in the us, these restrictions have been tightened as evidence of novel coronavirus community transmission mounted, from bans on groups of , to , to , to , to groups of any size. at times when community transmission is low in any given area, bans could be eased, raising the limit on attendance while requiring physical distancing to be practiced by attendees. physical distancing, particularly for long durations, can severely disrupt access to social and emotional supports. in another early court challenge to state social distancing measures, the plaintiff argued that new hampshire"s ban on large gatherings violates their first amendment rights to assembly and freedom of expression as well as fourteenth amendment right to due process. a suit filed in the eastern district of new york raised a similar challenge to new york"s gathering ban and stay at home order. by the end of march , more than half of states had gone further than banning gatherings by issuing mandates ordering residents to stay at home, with relatively broad exceptions for meeting essential needs and exercising outdoors, enforceable through criminal fines and jail time. while restrictions on gatherings are supported by public health emergency response guidelines, orders confining individuals to their homes are more controversial and have not been assessed as thoroughly in pandemic influenza planning. due to logistical constraints, even mandatory orders to stay at home are dependent on widespread voluntary compliance to be successful. compliance requires public acceptability and trust in government, which may be eroded if restrictions are harshly enforced or maintained for long durations. restrictions on assembly and involuntary confinement of individuals to their homes are typically subjected to the heightened judicial scrutiny, but may be justified by balancing the curtailment of individual liberty against compelling government needs. in the us, limitedduration curfews ordering individuals to stay indoors have occasionally been used by state and local officials to protect the public"s health and safety and prevent civil unrest in the event of natural disasters and other emergencies. courts reviewing challenges to covid- orders might also look to decisions upholding emergency orders restricting access to and movement within specified areas during limited periods of civil unrest. in , for example, a federal appellate court upheld an emergency restricted zone to protect public safety during a meeting of the world trade organization in downtown seattle. but long-term restrictions on activity outside the home by all residents without clear criteria or planning for when mandates might be eased or lifted are deeply problematic and require stronger justification that limited curfews or restricted zones. wholesale restrictions on personal movement do not allow for the individualized risk assessments courts have typically required to quarantine specific individuals infected or exposed to a communicable disease, as discussed below. though some restrictions, such as requirements to maintain a distance of at least six feet from non-household members, might be permissible in theory in light of the best available scientific evidence regarding the spread of novel coronavirus, enforcement on the ground could be highly problematic. even in the absence of prohibited discrimination based on race, ethnicity, or religion, a plaintiff could claim that spotty police enforcement was arbitrary and capricious. given that some local police departments have indicated they will be pursuing more proactive enforcement, threatening large fines and the possibility of jail time, the limits of public health authority to confine individuals could be tested in the courts as the pandemic continues to impact our lives in the months and years to come. some forms of travel restrictions and quarantine of individual travelers may be justified if they are truly necessary to protect people in areas with low community transmission from exposure to people who have recently traveled from areas with high transmission. guarded boundaries between or within us states and territories would raise difficult constitutional questions. bans on interstate travel imposed by state governments would have to navigate constitutional doctrines that constrain states from discriminating against non-residents and interfering with interstate commerce. the federal government has authority to close state borders pursuant to its authority to regulate interstate commerce, subject to individual rights constraints. limited geographic quarantines were established by local governments in some parts of the us more than a century ago to control bubonic plague. at least one lower federal court struck down a quarantine around a portion of san francisco, partly on the grounds that it discriminated against chinese americans and partly on the grounds that it confined the infected and the uninfected together without preventing the spread of disease within the cordon. reverse cordons with mandatory quarantine for all individuals permitted to enter from outside were established in some (mostly geographically isolated) local areas with low or no community transmission during the flu pandemic, and ad-hoc "shotgun quarantines" were adopted by some localities during yellow fever outbreaks in the south beginning in the s, but these measures do not appear to have been challenged in court. completely barring people from exiting an area severely affected by a disease outbreak, absent an assessment of the risks posed by individual travelers, would violate constitutional prohibitions against the deprivation of life and liberty without due process of law under almost every conceivable scenario. barring entry into an area where community transmission is low would implicate individual rights to travel. imposing a travelers" quarantine, as more than a dozen states have ordered for covid- , requiring individuals entering the area to be separated from others for a reasonable incubation period, would provide a less restrictive alternative to completely closed borders. mandatory restrictions in the absence of social supports to minimize secondary harms are deeply unjust. moreover, social supports maximize compliance with guidance and help maintain the public"s trust, bolstering the effectiveness of public health measures. upon initiation of school and workplace closures and guidance or orders to stay at home, governments should act immediately to ensure safe, sanitary, and accessible housing conditions for all. governmental responsibility should be exercised immediately to secure the health and safety of people in custody, detention, and foster care. wherever possible, people in custody should be released from crowded conditions and provided with supports for housing and other essential needs. people experiencing homelessness should be exempted from enforcement of mandatory orders to shelter in place (as most, but not all orders currently in effect have provided). moreover, safe, sanitary, and uncrowded shelter that is physically accessible for people with disabilities should be offered to people who are unhoused, experiencing homelessness, or living in communal settings. people who are experiencing domestic abuse should be proactively protected at a time when they may be cut off from outside contact and supports. safe and sanitary housing regulations should be proactively enforced to mitigate increased exposure to lead, mold, pest infestations, and other hazards, particularly for people living in low-income, federally-financed, or rental housing. federal, state, and local governments are acting to provide legal protections to preserve employment, income, housing, and utilities and financial assistance and direct delivery of essential goods and services for those in need. many of these measures are short-term, however. long-term measures may be required as the pandemic and our response to it unfolds in the coming months. over time, as community transmission is assessed to be minimal in some areas at some times, protective measures and accommodations will be particularly crucial for people who are at the highest risk of severe complications and death from covid- , who may need to stay at home even as others are able to return to work. though a relatively small number of vocal protesters have garnered media attention, the reality is that compliance with covid- community mitigation measures has been widespread and willing for the most part so far. due to logistical, legal, and ethical constraints, restrictions that are mandatory in theory rely on widespread voluntary compliance in practice. as levels of community transmission are assessed to be minimal in some places at some times, mandatory restrictions should be lifted and replaced with voluntary guidelines, but restrictions may need to be re-tightened periodically to keep the curve of the epidemic within health care capacity. throughout this crisis, sustained social supports to justify and enable safe compliance with restrictions and recommendations will be absolutely crucial to the success of the public health response to covid- . long-term, state-wide orders to close nearly all business operations and shelter in place were untested in us courts prior to the covid- pandemic. a small number of court precedents reviewing emergency communicable disease control measures and quarantines of individuals suspected of being exposed provide some guidance to courts reviewing challenges to covid- orders. in these pre-covid cases, judges evince a strong desire to defer to the scientific judgments of elected officials. in jew ho v. williamson, for example, judge william morrow assured authorities that he would "give the widest discretion" to actions taken "in the presence of a great calamity." but he also affirmed his grave constitutional responsibility to review government intrusions upon civil liberties. "is the regulation in this case a reasonable one?" he asked. "is it a proper regulation, directed to accomplish the purpose that appears to have been in view? that is a question for this court to determine." quarantines imposed on individuals, homes, and geographic districts were not an uncommon occurrence in the eighteenth and nineteenth centuries. cases adjudicating legal issues arising from quarantine orders were almost exclusively handled by the state courts, however, and federal rights were not widely understood to be implicated. at the turn of the twentieth century, federal courts began to hear challenges based on individual rights protected under the fourteenth amendment"s guarantees of due process and equal protection. in pre-civil rights era communicable disease control cases, judges applied standards of review that were considerably more deferential than the strict scrutiny standard that civil rights era precedents would later adopt for review of infringements upon fundamental rights and suspect classifications (such as those based on race, ethnicity, or religious affiliation). person to person and place to place and public health methods for combatting it. dr. stephen, who appears to have been invoked as an expert by the plaintiffs, averred that no proper or scientific precautions have been taken by [the san francisco board of health] to prevent the spread of … disease. [they] have proceeded from erroneous theories to still more erroneous and unscientific practices and methods of dealing with the same; for, instead of quarantining the supposedly infected rooms or houses in which … deceased persons lived and died, and the persons who had been brought in contact with and been directly exposed to said disease, [the] defendants have quarantined, and are now maintaining a quarantine over, a large area of territory, and indiscriminately confining therein between ten and twenty thousand people, thereby exposing, and they are now exposing, to the infection of the said disease said large number of persons. informed by dr. stephen"s affidavit, judge morrow demonstrated a remarkably nuanced understanding of the distinction between individual quarantines confining individuals "afflicted" with a highly communicable disease "to their own domiciles until they have so far recovered as not to be liable to communicate the disease to others" with "the object … to confine the disease to the smallest possible number of people" and geographic quarantine (also known as cordon sanitaire), whereby officials "place , persons in one territory, and confine them there," at which point "the danger of such spread of disease is increased, sometimes in an alarming degree, because it is the constant communication of people that are so restrained or imprisoned that causes the spread of the disease." morrow also decried the discriminatory character of the sanitary cordon, which operated almost exclusively against people of chinese descent. his order took a measured approach, lifting the general quarantine "thrown around the entire district" while affirming the authority of city officials "to maintain a quarantine around such places as it may have reason to believe are infected by contagious or infectious diseases." jacobson v. massachusetts, the case which the us supreme court upheld a compulsory vaccination mandate adopted during a smallpox outbreak, adopted a far more deferential posture toward the judgement of the massachusetts legislature and cambridge board of health as to matters of science. jacobson was also an emergency powers case, though it has been widely applied in non-emergency contexts, such as challenges to school vaccination mandates. the cambridge board of health adopted an adult smallpox vaccination mandate following its declaration of a local smallpox outbreak. thus, the court framed the case in terms of "authority to determine for all what ought to be done in an emergency." id. at . dr. stephen described himself as having "held various official positions, such as surgeon to the police, medical officer of health, parish medical officer, and public vaccinator," and having, "for the past thirteen years in the state of california," "given much time and study to the literature of the bubonic plague." he also noted that he was "the regularly appointed physician of the chines [sic] empire reform association, which numbers several thousand chinese residents in the state of california." id. at . id. id. at . u.s. ( ). id. at . the jacobson court grappled mightily with how to judge elected officials" adoption of compulsory public health measures in the absence of perfect information about risks and benefits. justice harlan"s opinion quoted a lengthy passage from a new york state court decision upholding a school vaccination mandate to prevent smallpox outbreaks: the appellant claims that vaccination does not tend to prevent smallpox, but tends to bring about other diseases, and that it does much harm, with no good….the common belief, however, is that it has a decided tendency to prevent the spread of this fearful disease, and to render it less dangerous to those who contract it…. the possibility that the belief may be wrong, and that science may yet show it to be wrong, is not conclusive; for the legislature has the right to pass laws which, according to the common belief of the people, are adapted to prevent the spread of contagious diseases…. while we do not decide, and cannot decide, that vaccination is a preventive of smallpox, we take judicial notice of the fact that this is the common belief of the people of the state, and, with this fact as a foundation, we hold that the statute in question is a health law, enacted in a reasonable and proper exercise of the police power. jacobson upheld the compulsory vaccination mandate as consistent "with the liberty which the constitution the united states secures to every person against deprivation by the state." justice harlan recognized that individual liberty is not "an absolute right in each person to be, in all times and in all circumstances, wholly free from restraint." rather, "every wellordered society charged with the duty of conserving the safety of its members the rights of the individual in respect of his liberty may at times, under the pressure of great dangers, be subjected to such restraint, to be enforced by reasonable regulations, as the safety of the general public may demand." harlan upheld the emergency vaccination mandate on the grounds that the board of health reasonably believed "it was necessary for the public health or the public safety." in closing, however, harlan "observe[d]… that the police power of a state … may be exerted in such circumstances, or by regulations so arbitrary and oppressive in particular cases, as to justify the interference of the courts to prevent wrong and oppression." the court declined to "usurp the functions of another branch of government," by "adjudg[ing], as matter of law, that the mode adopted under the sanction of the state, to protect the people at large was arbitrary, and not justified by the necessities of the case." but its decision also recognized that the "acknowledged power of a local community to protect itself against an epidemic threatening the safety of all might be exercised in particular circumstances and in reference to particular persons in such an arbitrary, unreasonable manner, or might go so far beyond what was reasonably required for the safety of the public, as to authorize or compel the courts to interfere for the protection of such persons." surprisingly many courts have continued to employ jacobson"s pre-civil rights era standard of "non-arbitrary and justified by public health necessity" (with "necessity" not being used in the strict sense of the word) to judge routine compulsory public health measures (especially school vaccination mandates) while declining to decide whether strict scrutiny applies. lower federal court decisions on challenges to individual quarantine orders for smallpox and ebola virus disease are also instructive for judges fielding covid- constitutional challenges. although these cases have been decided during and after the civil rights era, in which courts recognized the importance of more searching judicial review to protect fundamental rights to liberty, their approach to scrutinizing emergency communicable disease control orders has been non-strict in ways that mirror jacobson and jew ho (though without necessarily citing them). in , the federal district court for the eastern district of new york declined to release ellen siegel from a federal quarantine facility where she was being held after visiting stockholm, sweden at a time when it was designated a "small pox infected local area" by swedish health authorities. in us ex rel. siegel v. shinnick, judge john francis dooling, jr. carefully reviewed the international sanitary regulations adopted by the world health organization (who), which deferred to the declarations of local health officials as to when a local area is "free of local infection." he also noted who guidelines indicating that declaration of local infection could be safely terminated "twenty-eight days after the last reported case of small pox dies, recovers or is isolated." siegel argued that the designation of stockholm as affected by smallpox at the time of her visit was in error because (as both parties agreed) the most recently reported case had later been determined to be a false positive. dooling could have done the math himself and determined that, following who guidelines, stockholm could have ( - ) . but these orders do not trigger the same degree of deference from courts that emergency orders adopted under conditions that limit the feasibility of rigorous scientific risk assessments and so i do not address them here, given limits on space. been designated safe from smallpox prior to siegel"s arrival. but instead he deferred to swedish health authorities: it does not appear that others are legally competent to (as they would be hopelessly handicapped in seeking to) make a determination on such a question as whether or not stockholm can now be regarded as not an infected local area on the basis that the last reported case went into isolation [more than days prior to siegel"s arrival]; responsibility for applying that standard rests with the territorial health administration and depends on whether, also, all measures of prophylaxis have been taken and maintained to prevent recurrence of the disease. it is idle and dangerous to suggest that private judgment or judicial ipse dixit can, acting on the one datum of the date june as the last identified and reported case, undertake to supercede [sic] the continuing declaration of the interested territorial health administration that stockholm is still a small pox infected local area. although he deferred to swedish health authorities" designation of stockholm as an affected area, judge dooling carefully reviewed the actions of the federal public health service, which ordered siegel"s quarantine upon her return to the us. in upholding the quarantine order, dooling pointed to the importance of an individualized risk assessment, "taking into account previous vaccinations and the possibilities of her exposure to infection." siegel was initially asked to present a certificate of vaccination against smallpox, but she had failed to produce detectable antibodies following a series of vaccination attempts and could not be certified as successfully vaccinated. dooling noted that federal health officials had not detailed siegel"s husband, who apparently had been successfully vaccinated prior to the trip to stockholm. the judge also emphasized the need to adopt less restrictive alternatives, where available. he urged "caution[] against light use of isolation," which "is not to be substituted for surveillance unless the health authority considers the risk of transmission of the infection by the suspect to be exceptionally serious." the order in siegel was, however, highly deferential to federal health officials" scientific risk assessment based on the best available evidence and relying on the precautionary principle. dooling noted that "the judgment required is that of a public health officer and not of a lawyer used to insist[ing] on positive evidence to support action; their task is to measure risk to the public and to seek for what can reassure and, not finding it, to proceed reasonably to make the public health secure. they deal in a terrible context and the consequences of mistaken indulgence can be irretrievably tragic. to supercede [sic] their judgment there must be a reliable showing of error." men" who testified on behalf of the federal defendants as "shar[ing] a concern that was evident and real and reasoned." in a footnote, dooling noted that the procedure followed by health officials was not directly constrained by federal or international regulations, but "remains a function of the gravity of the situation as measured by their expert judgments dispassionately formed." his description of the defendant"s "expert" and "dispassionate[]} determinations as not only reasoned but "evident and real" appears to be consistent with the "non-arbitrary and justified by the necessities of the case" standard applied by the jacobson court. more recently, state and federal courts fielded two lawsuits involving kaci hickox, a nurse who, upon her return from treating ebola patients in sierra leone, was briefly detained by federal health authorities for a health screening at newark international airport, then handed over to new jersey officials who held her under a state quarantine order, then released to her partner"s home state of maine where the governor ordered state troopers to guard her home and follow her movements while health officers from the state"s center for disease control monitored her temperature and symptoms daily. first, a state trial judge in maine was asked to impose a court-ordered home quarantine, which hickox resisted on the grounds that it was not based on a reasonable assessment of the risk she posed to others. hickox later filed a suit for damages in the federal district court in new jersey. in hickox v. mayhew, maine state trial court judge charles laverdiere, followed his predecessors in looking to guidelines from health agencies. in the press, hickox argued that because that she did not have any symptoms and the best available evidence demonstrated that transmission by asymptomatic individuals was not a concern, an involuntary quarantine was inappropriate. judge laverdiere ultimately determined that hickox could properly be subjected to an order mandating direct active monitoring (with direct observation by state health authorities at least once per day to review symptoms and monitor temperature with a second daily follow-up by phone), a less restrictive limitation on her liberty than the home quarantine restrictions the state had requested. in reaching this result, the judge noted that "the only information that the court has before it regarding the dangers of infection posed by" hickox, was from the affidavit of "shiela pinette, d.o., director of the maine center for disease control and prevention, together with the attachments from the u.s. centers for disease control." in particular, both parties agreed that hickox was "asymptomatic (no fever or other symptoms consistent with ebola), as of the last check pursuant to her direct active monitoring." judge laverdiere followed dr. pinette"s conclusion that the imposition of direct active monitoring was functionally dictated by cdc"s (voluntary) guidelines: "therefore the guidance issued by u.s. cdc states that she is subject to direct active monitoring. health care workers in the "some risk" category require direct active monitoring for the -day incubation period." in his concluding "observations," laverdiere noted that he was "fully aware of the misconceptions, misinformation, bad science and bad information being spread from shore to shore … with respect to ebola" and "that people are acting out of fear and that this fear is not entirely rational. however, whether that fear is rational or not, it is present and it is real." the judge chided hickox to ensure that her "actions at this point, as a health care professional, need to demonstrate her full understanding of human nature and the real fear that exists" and "guide herself accordingly." in a subsequent suit arising out of her initial quarantine in new jersey, hickox"s constitutional arguments were rejected, but she eventually reached a settlement on state law grounds that included new protections for people quarantined in new jersey. in hickox v. christie, federal district court judge kevin mcnulty had the benefits of time and hindsight. he fielded the suit for damages several months after the quarantine on hickox had been lifted, when it was clear that she never contracted ebola virus and ebola panic among americans had passed. still, judge mcnulty relied on cdc guidance to justify the state"s quarantine. noting that he did "not need to make any finding as to its accuracy," he "simply note[d] that the authorities could reasonably have relied on it" at the time they detained hickox. unlike laverdiere, mcnulty took a somewhat more skeptical stance toward cdc guidance, which adopted a less cautious approach toward exposed but asymptomatic individuals than new jersey officials applied. mcnulty pointed out that cdc guidance did not automatically dictate how hickox should have been handled, because the guidance "contain[ed] recommendations, and it note[d] the importance of public health officials" exercise of their judgment." mcnulty declined to formally endorse requirements of individualized risk assessments and the least restrictive means, which public health law experts have urged are constitutionally required for mandatory quarantines of individuals believed to pose a risk of transmitting communicable disease. he "assume[d] without deciding that the… "individualized assessment" of the individual"s illness and ability or willingness to abide by treatment can, mutatis mutandis, be adapted to the situation of a temporary detention for observation based on a risk of infection." ultimately, he concluded that "an erroneous application of cdc guidelines does not correspond to a constitutional cause of action." federal guidelines have struggled to keep pace with the restrictions imposed by governments in response to the spread of sars-cov- . with respect to community mitigation and non-pharmaceutical interventions, on march , cdc quietly posted a document titled "implementation of mitigation strategies for communities with local covid- transmission." described as "a framework for actions which local and state health departments can recommend in their community to both prepare for and mitigate community transmission of covid- ," this document recommended that "these actions should be guided by the local characteristics of disease transmission, demographics, and public health and healthcare system capacity." in places with "substantial" community transmission, defined as occurring when there is "[l]arge scale community transmission," with "healthcare staffing significantly impacted, multiple cases within communal settings like healthcare facilities, schools, mass gatherings etc.," the framework recommended that "[a]ll individuals should limit community movement and adapt to disruptions in routine activities (e.g., school and/or work closures) according to guidance from local officials." the framework additionally recommended that in periods of substantial community transmission, organizations should "cancel community and faith-based gatherings of any size." separately, cdc issued guidelines for large community events and mass gatherings recommending cancellation of "gatherings of more than people for organizations that serve higher-risk populations." notably, even as nearly every state issued mandatory orders restricting the operation of commercial businesses, cdc"s only guidance for "keeping commercial establishments safe" recommended disinfection of surfaces, steps to stagger customer flow and frequent hand washing, while the cdc website suggested businesses "[c]onsider establishing policies and practices for social distancing … if recommended by state and local health authorities." in mid-march, cdc also issued a series of specific guidance documents for specific localities and states, including the cities of santa clara, seattle, and new rochelle, and the states of florida and massachusetts. notably the cdc guidance for santa clara recommended "laser focused" and less restrictive interventions that were inconsistent with the county-wide shelter-in- place order the santa clara health officer issued a day earlier. cdc guidance for other locations similarly recommended less stringent measures than state and local authorities had already adopted. the white house issued competing guidance on march . the " days to stop the spread" guidelines, later amended to " days," recommended that certain groups-people who feel ill, people who test positive for coronavirus and their family members, and people who are older or who have serious underlying health conditions that put them at increased risk-should stay at home. it also recommended that everyone should "avoid social gatherings in groups of more than people," "eating or drinking at bars, restaurants, and food courts," and "discretionary travel, shopping trips, and social visits." with respect to closures, the guidelines noted that "[g]overnors in states with evidence of community transmission should close schools in affected and surrounding areas" and "[i]n states with evidence of community transmission, bars, restaurants, food courts, gyms, and other indoor and outdoor venues where groups of people congregate should be closed." this guidance adopted a far less cautious stance toward mitigating the spread of novel coronavirus than the mandatory stay-at-home and non-essential business closure orders in effect in the majority of states at the time the white house guidelines were released. subsequently, on april , the white house released new "guidelines for opening up america again," which set forth a phased approach to resuming social gatherings, resuming elective medical procedures, and reopening schools and the types of businesses that the previous white house guidelines had recommended for closure (including bars, restaurants, gyms, and venues where groups of people gather).. the guidelines established "gating" criteria for reopening "large venues" and gyms after a sustained downward trajectory in the number of syndromic and reported cases for days and at a point when hospitals are able to treat patients without resorting to crisis standards of care and to test health care workers exposed to novel coronavirus. if the same gating criteria are met following the reopening of gathering places in phase one, states were advised to proceed to phase two, in which schools, bars, and other higherrisk settings are reopened. the few courts that have reviewed early covid- civil liberties challenges to date have followed pre-covid precedents in relying on voluntary guidelines from international and federal authorities, but that may prove more challenging as restrictions imposed by state and local governments exceed what cdc has endorsed, particularly given that the white house is offering guidelines that conflict with cdc"s. in binford v. sununu, a new hampshire state trial court upheld the state"s ban on gatherings of or more people (new hampshire later lowered the limit for groups) and prohibition of dine-in service at bars and restaurants, rejecting the plaintiffs" argument that these restrictions impermissibly infringed upon his rights under the first and fourteenth amendments. in an opinion issued on march , nine days after the white house"s " days to stop the spread" guidance went into effect, judge john c. kissinger noted that these restrictions were "clearly supported by the recommendations put forth by the white house and cdc" without specifying which recommendations were applicable. judge kissinger undoubtedly reached the right result in upholding the ban on gatherings of or more people, but he based his holding on troubling reasoning. adopting the position that the governor has "authority to suspend civil liberties" in an emergency, the court applied a "good faith/some factual basis" test to uphold the restrictions. this test, which comes from an th circuit case upholding a nightly curfew in miami-dade county in the aftermath of hurricane andrew, eschews the courts" constitutional responsibility to determine whether the state has adopted "a proper regulation, directed to accomplish the purpose that appears to have been in view?" in the words of judge morrow in jew ho. the lack of clear guidelines from cdc supporting the state"s reasonable measure may have played a role in judge kissinger"s decision to resort to the extreme of adopting a suspension rule. in its objection to the plaintiff"s complaint, the state did not argue for suspension. it cited the th circuit hurricane case, but without specifically referring to or endorsing the suspension rule. the state also cited specific cdc and white house guidelines, which it described as recommending cancellation of planned gatherings of or more people, but (as noted above) the cdc"s guidance was limited to organizations "that serve higher risk populations" and neither guideline specifically endorsed mandatory limits on bar and restaurant service. in a situation where conflicting guidelines have been issued, a court applying a rational basis test or jacobson"s standard should defer to the choice of a political branch to follow the more cautious guidelines. in challenges based on civil liberties, this will typically result in upholding restrictions. but at the time binford was decided, no federal guidelines recommended bans on gatherings for the general population, leaving the state with little cover to defend its ban. in a higher profile case, the fifth circuit upheld application of the texas emergency order prohibiting elective medical care to all abortions, partially on the grounds that cdc had recommended preserving face masks and the centers for medicare and medicaid services had binford v. sununu, supra note . recommended limiting unnecessary medical procedures to reduce opportunities for disease transmission. in re abbott relied on a warped characterization of jacobson as establishing "the controlling standards, established by the supreme court over a century ago, for adjudging the validity of emergency measures." the majority set aside the heightened review typically applied to restrictions on abortion in favor of a rule that "the scope of judicial authority to review rights-claims" during "a public health crisis" is limited to cases where "a statute purporting to have been enacted to protect the public health, the public morals, or the public safety, has no real or substantial relation to those objects, or is, beyond all question, a plain, palpable invasion of rights secured by the fundamental law." moreover, the fifth circuit suggested that in a crisis, this minimal level of scrutiny applies equally to "one"s right to peaceably assemble, to publicly worship, to travel, and even to leave one"s home." although not explicitly endorsing a suspension principle, in re abbott"s manipulation of jacobson achieves essentially the same result: applying an exceedingly low standard of review in times of crisis. as robert gatter argued in his critique of ebola quarantine cases, judges" "responsibility to assure [relevant scientific] facts are discovered and accounted for … is inherent in even the most deferential standard of judicial review. a court asked to address whether a public health agency has acted reasonably and without abusing its discretion need not simply defer to the expertise of the agency without requiring that the agency to identify and explain the logic the agency deployed to reach its conclusion that quarantine was appropriate." the same is true of officials charged with developing emergency communicable disease control guidelines that, while technically voluntary, are likely to be relied on to enforce involuntary-and highly intrusive-measures by state and local governments. clear guidelines developed by cdc through transparent processes that include publication of peer reviewed analyses and literature reviews give states important cover for defending emergency orders in the face of civil liberties challenges. in the absence of an "easy" route to defending state and local restrictions as consistent with evidence-based guidelines, judges who wish to uphold emergency orders may resort to less searching forms of review. though the result-upholding the restrictions-may be the right one in most cases, a knee-jerk approach that endorses a governor"s authority to suspend the civil liberties protected by the federal constitution will not be helpful to developing a sustainable long-term strategy for mitigating the current pandemic or for future public health law preparedness efforts. as the fifth circuit"s coronavirus abortion decisions demonstrate, when courts abandon the ordinary levels of even if conflicting guidelines are released-as has been the case with separate sets of covid- guidelines coming from the white house and the cdc-courts following jacobson"s standard of review should defer to elected officials" choice as to which guidelines they adopt. a cautious set of guidelines may provide adequate cover to states to enforce some forms of community mitigation even if alternative, less cautious guidelines are available. and if a higher standard of review applies, as is the case for abortion restrictions, then the availability of a less restrictive alternative can and should lead courts to question the necessity of harsh limits. governments must earn the public"s trust by acting transparently, fairly, and effectively and communicating their plans and guidance clearly. the way we respond to the covid- crisis-how state and local governments wield authoritarian powers necessary to combat the spread of disease and how we protect the people who are most vulnerable to the disease itself and the secondary harms that will arise out of our efforts to combat it-will shape public health law and the society we live in for generations to come. ) (dismissing suit for damages by class of individuals quarantined under state orders in connecticut nurse says she won't have officials violate 'my civil rights new jersey accepts rights for people in quarantine to end ebola suit for a critical assessment of cdc"s ebola guidance and its effect on related court decisions, see robert gatter, ebola, quarantine, and flawed cdc policy, u. miami bus. l. rev. ( ); see also robert gatter, three lost ebola facts and public health legal preparedness cdc, implementation of mitigation strategies for communities cdc, resources for large community events & mass gatherings what every american and community can do now to decrease the spread of the coronavirus interim guidance for businesses and employers to plan and respond to coronavirus disease s recommendations for day mitigation strategies for days to slow the spread was later revised and replaced with days to slow the spread, the president's coronavirus guidelines for america trump announces guidelines for opening up america again guidelines: opening up american again citing centers for disease control and prevention three lost ebola facts, supra note key: cord- -rxg sjd authors: allcott, hunt; boxell, levi; conway, jacob; gentzkow, matthew; thaler, michael; yang, david title: polarization and public health: partisan differences in social distancing during the coronavirus pandemic date: - - journal: j public econ doi: . /j.jpubeco. . sha: doc_id: cord_uid: rxg sjd abstract we study partisan differences in americans’ response to the covid- pandemic. political leaders and media outlets on the right and left have sent divergent messages about the severity of the crisis, which could impact the extent to which republicans and democrats engage in social distancing and other efforts to reduce disease transmission. we develop a simple model of a pandemic response with heterogeneous agents that clarifies the causes and consequences of heterogeneous responses. we use location data from a large sample of smartphones to show that areas with more republicans engaged in less social distancing, controlling for other factors including public policies, population density, and local covid cases and deaths. we then present new survey evidence of significant gaps at the individual level between republicans and democrats in self-reported social distancing, beliefs about personal covid risk, and beliefs about the future severity of the pandemic. facing the precinct specification (see footnote ). to complement the data showing county-level differences in behavior, we use a nationally-representative survey to show that individual behavior and beliefs about social distancing are partisan. we collect participants' demographics (including party affiliation), beliefs regarding the efficacy of social distancing, self-reported distancing due to , and predictions about future covid- cases. compared to republicans, we find that democrats believe the pandemic is more severe and report a greater reduction in contact with others. in our survey, we also randomly vary whether predictions about future covid- cases are incentivized. we do not find evidence that incentives reduce the partisan gap, suggesting that these predictions are less likely to be due to partisan cheerleading (as in bullock et al. and prior et al. ) and more likely to reflect true differences in beliefs. these partisan gaps in survey responses emerge even when comparing respondents within the same county. a number of contemporaneous studies also measure partisan differences in responses to gadarian et al. ( ) , makridis and rothwell ( ) , and wu and huber ( ) show that partisanship is a primary driver of attitudes about the pandemic and self-reported behaviors in surveys, and druckman et al. ( ) show that affective polarization colors people's evaluations of the u.s. government response to the pandemic. cornelson and miloucheva ( ) , grossman et al. ( ) , and painter and qiu ( ) demonstrate partisan differences in response to state-level stay-at-home orders. barrios and hochberg ( ) show differences between republican and democratic areas in the frequency of covid-related queries on google and in movement patterns as measured in gps data from a different source than the one we use. fan et al. ( ) find differences in risk perceptions and social distancing in gps and survey data across political parties and other demographics. our results are broadly consistent with these other studies, but we believe that our paper contributes to the discussion through a unique combination of observational data analysis, survey work, and a theoretical model that helps understand the economic implications of our results. ash et al. ( ) , bursztyn et al. ( ) and simonov et al. ( ) find that people social distance less if quasi-randomly exposed to news sources that argue that covid- is less risky, suggesting that media exposure is one possible driver for our results. our work contributes to a broader literature on what drives responses to pandemics (e.g., blendon et al. ; vaughan and tinker ; fineberg ) . mobilizing an effective public response to an emerging pandemic requires clear communication and trust (holmes ; taylor et al. ; van der weerd et al. ; vaughan and tinker ) . risk perception, behavior changes, and trust in government information sources change as pandemics progress (ibuka et al. ; bults et al. ) . demographic characteristics, such as gender, income, geography, or social interactions, are important determinants of the adoption of recommended public health behaviors (bish and michie ; ibuka et al. ; bults et al. ; chuang et al. ; shultz et al. ; gamma et al. ) . a related literature focuses on the consequences of political polarization for health behaviors (e.g. finally, our work relates to broader literatures on partisan differences in trust and beliefs (e.g., bartels ; gaines et al. ) and adds to the increasing number of papers using gps or related data to study social interactions (e.g., dubé et al. ; chen and rohla ; athey et al. ) . sections , , , and , respectively, present our theoretical framework, data, gps analysis, and survey results. in this section, we present a stylized model to clarify why it might matter if different types of people choose different amounts of social distancing. we embed an epidemiological model of disease transmission into an economic model with agents who maximize utility considering the expected private cost of disease. we consider how heterogeneity in perceived risks affects aggregate welfare. we use a discrete-time version of the standard sir epidemiological model (kermack and mckendrick ) . in each period t, each person is in one of four states { , , , } s i r d   , representing susceptible, infected, recovered, and deceased. the share of the population in each state at time t is t s , t i , t r , and t d . let  represent disease infectiousness, and let t c denote an individual's amount of risky behavior at time t-for example, the amount of travel, dining out, failing to wash hands, and other activities that increase the risk of becoming infected. all people begin in the susceptible state. a susceptible person becomes infected at time t  with probability tt ci  and stays susceptible with probability ( note that this also implicitly depends on current and future population states t   . being infected reduces utility, so we assume ( ) > ( ) v s v i  for any given current population state. we focus on susceptible people, as they comprise most of the population during the period we study and are the people who face a trade-off between the benefit of consumption and the risk of becoming infected. we can write their maximization problem as a bellman equation, in which people maximize the sum of utility from risky behavior today and expected future utility:   current utility from risky behavior expected future utility ( ) the first-order condition for privately optimal risky behavior is ( ) the first-order condition shows that people choose their risky behavior to equate marginal benefit (more utility today) with private marginal cost (higher risk of infection, which reduces future utility). the equation illustrates that there are three reasons why risky behavior might vary across types. first is the marginal utility of risk (or equivalently, the marginal cost of social distancing): for example, people vary in how much they like travel and dining out, as well as in how easy it is to work from home. second is the marginal infection probability: for example, local infection rate t i differs across geographic areas. third is the private cost of infection: for example, infection is more harmful for people who are older or have underlying health conditions. it is difficult to know for sure whether people take too many or too few steps to reduce disease transmission during our study period. thus, we do not consider the optimal consumption of c. instead, we hold constant the total amount of risky behavior and ask whether the allocation across types is optimal. tangibly, this means that we are not asking, "how much social distancing should people be doing?" instead, we are asking, "holding constant the amount of social distancing people are doing, would some people ideally be doing less, and others ideally be doing more?" social welfare is the sum of utility across all people in all states: let t c denote the total risky behavior at time t across all people. the (constrained) socially optimal outcome results from maximizing t w subject to the constraint that = tt cc . let  be the shadow price on that constraint; this reflects the loss from having too much or too little social distancing overall. consuming c imposes two types of externalities. first, it imposes a positive pecuniary externality, as travel, dining out, and other risky activities help keep firms in business and workers employed. second, it imposes a negative externality by increasing the person's infection probability, which increases the expected stock of infected people in the next period ( t i  ) and then increases other susceptible people's infection risk. let t  denote the net externality per unit of consumption, which may be positive or negative; this becomes more negative as the contagion externality grows. we assume that these externalities are constant across people and that people do not account for the externalities when choosing * t c . j o u r n a l p r e -p r o o f we now allow people to misperceive risks. these misperceptions cause susceptible people to choose too much or too little risky behavior relative to their private optimum, and heterogeneous misperceptions cause transfers across types and efficiency losses. we now add  subscripts to explicitly denote different parameters by type. let intuitively, type a people (democrats) are doing too much social distancing, and type b (republicans) too little, relative to the (constrained) social optimum with homogeneous risk perceptions. since the marginal cost of social distancing is increasing, society could achieve the same amount of social distancing at lower cost if type a did less and type b did more. this model informs the empirical tests in the rest of the paper. in sections and , we ask if democrats and republicans are reducing risk by different amounts. we use proxies to control for differences in actual risks and differences in the marginal costs of risk reduction-both of which could cause differential risk reduction to be socially optimal. in section , we ask if democrats and republicans have different risk perceptions, which would generate the transfers and efficiency costs described above. in these analyses, we control for factors such as population density, health risks, and local coronavirus cases that could generate difference in actual risks across types. we also give a back-of-the-envelope estimate for the efficiency cost of heterogeneous misperceptions. our analysis uses data from safegraph, aggregating gps pings from about million mobile devices and numerous applications to measure foot traffic patterns to a collection of points-of-interest (pois). pois include retail shops, restaurants, movie theaters, hospitals, and many other public locations individuals may choose to go when leaving their house. for each poi, safegraph reports its geographic location, industry, and the total number of visitors in their mobile device panel that have visited each day. our primary analysis uses data from a period of weeks, from january to july , . we aggregate visits across all pois in a given county and week. we also separately aggregate visits by -digit naics code for each county and week. in a placebo analysis, we analyze data over earlier time periods (starting in january ). we also use data from the safegraph social distancing data released as a part of their covid- response. this data is available since january , and updated regularly. we use data over the same week period. this data contains alternative measures of social distancing beyond poi visits, such as the number of devices leaving their assigned geohash- home, the number of other census block groups visited, or the median time spent away from home across devices. we supplement the safegraph data with various other sources of county and census block group data. for demographic information on age, race, education, income, occupation, and poverty status at the county-level, we aggregate census block group data from safegraph open census to the county level. we add weather statistics on temperature and precipitation from gridmet (abatzoglou ) , aggregated to the county-level. for each county, we define county partisanship to be the proportion of total votes received by president donald trump in the election (mit election data and science lab ). we use county-level data on covid- cases and deaths from the new york times ( ). we also add data on county or state stay-at-home policies from a variety of sources (as in allcott et al. ). to supplement these data, we ran an online survey with a sample of american adults to study partisan gaps in beliefs about and responses to covid- at the individual level. the survey was conducted from april - , with prime panels from cloudresearch, a market research firm with access to million participants. we recruited , participants to complete the study. participants are broadly representative of u.s. adults in terms of party affiliation, age, gender, and race. in addition, we weighted observations so that age, gender, and race distributions match census data and party affiliation matches recent gallup polling data (gallup ). participants were asked for their party affiliation on a seven-point scale, ranging from "strongly democratic" to "strongly republican." we transform the seven-point party affiliation scale to range between (strongly democratic) and (strongly republican), with intermediate values equally spaced. the survey asked for demographic information (zip code, age, race, gender, income, education, number of children, and health characteristics). it then asked about news consumption habits and trust before and during covid- . then, there were several questions about social distancing: self-reported social distancing in response to covid- , beliefs about the risk of not distancing, and the appropriate trade-off between going out more to help the economy versus going out less to avoid spreading covid- . we next elicited beliefs about the number of new covid- cases that would be confirmed in the us in april, , with , subjects ( percent) being financially incentivized for predictions that are closer to the correct answer. the remaining ( percent) of subjects were not incentivized. the primary four outcome variables are participants' answers to the three social-distancing questions and the one prediction question. these analyses correspond to the "main analyses" in our pre-analysis plan (aea rct registry ). in the interest of space, we do not discuss the plan's "exploratory analyses" in this paper. the safegraph open census data is derived from the -year acs at the census block group level. we thank jude bayham for sharing aggregated versions of this dataset with the safegraph covid- response community, originally constructed for burkhardt et al. ( ). we combine policy data from: keystone strategy; a crowdsourcing effort from stanford university and the university of virginia; hikma health; and the new york times. participants who made financially incentivized predictions were told that we would randomly select participants who would receive a payment of ($ ), where  is the percentage point difference between their answer and the true value. journal pre-proof figure presents geographic variation in social distancing, partisanship, covid- incidence, and stay-at-home orders. panels a and b illustrate a strong geographic correlation between the counties with weaker social distancing responses during the week of peak social distancing (april - , ) and those with higher republican vote shares. however, partisanship is also strongly correlated with covid- incidence (panel c) and earlier stay-at-home orders (panel d). figure reports trends in social distancing and covid- incidence separately for republican and democratic counties. panel a shows that the overall number of poi visits was relatively constant until covid- cases begin emerging in the united states in march. mobility levels then fell until reaching a minimum during the week of april - , , followed by a gradual recovery that remained below pre-pandemic levels as of july - , . throughout this pandemic period, democratic counties exhibited a larger drop in weekly poi visits than their republican counterparts with this partisan gap generally growing over time. however, as panel b demonstrates, democratic counties also exhibited a larger rise in covid- cases and deaths. appendix figure a shows that, over the same time period in , poi visits displayed a noticeable but smaller partisan gap. our main empirical specification takes the following form  is the county-specific error term. we chose our covariates it x to flexibly control for the four channels of divergent behavior highlighted in equation ( ) . standard errors are clustered at the state-level throughout unless specified otherwise. figure reports our estimates of t  under various sets of covariates chosen to incrementally control for the mechanisms highlighted by our model. in panel a, we only include county and time fixed effects. this measures the extent to which these two groups' behavior diverges with the rise of covid- via any of the aforementioned channels. throughout february, there are no significant partisan differences in poi visits relative to the january week baseline. however, as covid- begins to emerge in the united states, partisan differences arise and grow throughout the weeks of march and persist at least through early july. these results do not control for differences in public policies, which themselves may be a function of the partisan leanings of government officials. in panel b, adding state-time fixed effects to control for state-level policies in response to covid- along with other state-level temporal shocks causes the partisan differences to attenuate only slightly. in panel c, we flexibly control for various health, economic, and weather characteristics of the county. we view the health controls as proxies for the marginal infection probability and the private cost of infection, and we view the economic controls as proxies for the marginal cost of social distancing, though each group of controls could proxy for other factors as well. we include these controls nonparametrically via indicators for decile bins within a week, which we interact with time fixed effects in order to allow the coefficients on these indicators to vary flexibly across time. although these controls attenuate partisan differences, they remain economically and statistically significant. appendix figure a shows that these strong partisan differences do not appear over the same time period in conditional on the same controls. these results are consistent with behavioral differences driven by partisan misperceptions of risks at the group-level. to better understand the magnitudes of this partisan gap, we compare the difference between very republican and very democratic counties to contemporaneous mobility levels and to overall social distancing relative to january. the estimate of our partisan gap coefficient t  is . by the week starting april (the week with the fewest number of visits) and . in the week starting may (the week with the largest partisan gap). these estimates imply that going from a county with the th to the th percentile in republican vote share is associated with . and . percent increases in the number of poi visits during these two weeks respectively. the . percent gap during the week of april corresponds to . percent of the total change in poi visits between the weeks of january and april , and the partisan gap during the week of may is comparable in size to . percent of the total change in poi visits between the weeks of january and may . the partisan gap in social distancing between very republican and very democratic counties is economically meaningful but only accounts for a limited portion of overall social distancing. in appendix figure a , we report sensitivity to various alternative specifications. panels a and b use alternative sets of controls. panel c replaces the measure of partisanship with a discrete indicator for certain quantiles of the republican vote share distribution. panel d drops counties that are very small (less than , people), very large (greater than , people), or are in states with early covid- outbreaks (california, washington, and new york). panel e restricts the sample to counties from certain portions of the republican vote share distribution. panel f weights observations by the county's population, uses standard errors clustered at the county-level, and examines sensitivity to the start date. except when restricting to counties in the top half of the republican vote share, none of the alternative specifications change the central conclusion regarding partisan differences in social distancing in march through at least early july. health controls include: an indicator for whether a county has been under a stay-at-home order; log of one plus the number of confirmed covid- cases in the county; log of one plus the number of covid- deaths in the county; log of one plus the county population density (individuals per square kilometer); and share of the population age +. economic controls include: share of the population with at least a bachelor's degree; share in poverty; share with household income  $ , ; shares white, black, and asian; share commuting by public transportation; share currently enrolled in undergraduate study; and shares of occupations in various categories (management, business, science, and art; services; sales and office occupations; natural resources, construction, and maintenance). weather controls include daily high temperature, daily low temperature, and amount of precipitation averaged across days within a week. the difference between the th and th percentile of republican vote share is . - . = . . between the weeks of january and april (may ), poi visits decreased by . ( . ) percent. we compare the fraction of this overall change equivalent to our th vs. th percentile partisan gap: appendix figure a aggregates the number of poi visits at the electoral precinct level and shows similar partisan gaps, even when including county-time fixed effects. again, these patterns are not present in (appendix figure a ). precinct-level analysis faces several limitations that lead us to prefer our county-level specification. appendix figure a examines heterogeneity across industries by aggregating poi visits to the county level after restricting to certain -digit naics codes. consistent with the narrative around covid- , we see the strongest partisan differences emerge with pois in the accommodations and food, entertainment, and retail industries. the partisan differences in visits to health care pois are generally smaller and are statistically significant in fewer weeks. appendix figure a repeats panel c of figure , but uses poi visits aggregated at the day level. the partisan differences emerge for both weekdays and weekends, suggesting these differences are not driven solely by differences in work-from-home policies. appendix figure a considers alternative measures of social distancing derived from safegraph's social distancing data. statistically significant partisan differences emerge in march through at least early july for the log number of devices leaving home, the log number of stops made in non-home census block groups, the log of the median time away from home (panel a), and the share of devices leaving home (panel b). in panel c, we conduct our alternative social distancing analysis at the precinct level while including county-time fixed effects. for the log number of devices leaving home and the log number of stops made in non-home census block groups, we find an economically and statistically significant partisan gap emerge starting in april and persisting through early july (though see footnote for limitations of the precinct-level analysis). turning to the results of our survey, we first confirm that individuals' beliefs related to covid- are strongly associated with their social distancing behaviors. we find that a one standard deviation (sd) increase in beliefs about the efficacy of social distancing, as described below, is associated with a . sd increase in self-reported social distancing (se . ; p < . ), controlling for demographic characteristics and state fixed effects. similarly, a one sd increase in beliefs about the number of future cases in the us is associated with a . sd increase in self-reported social distancing (se . ; p = . ). next, we show that there exist individual-level partisan differences in (self-reported) social distancing behaviors and attitudes, consistent with the gps analysis presented above. we then show that beliefs about the effectiveness of social distancing and predictions of the spread of covid- follow the same partisan patterns. our main empirical specification regresses normalized responses on party: we note several limitations of our precinct-level analysis. due to the limited availability of precinct-level shapefiles, our precinct-level analysis includes only states (see appendix a. . ). partisanship is measured at the precinct-level, while social distancing and our health, weather, and economic controls are generally measured at the census block group level. the latter set of variables are then mapped to precincts based on geographic overlap using the procedure described in appendix a. . , potentially introducing correlated measurement error between our outcome and non-partisanship controls. finally, poi visits are allocated to geographies by merchant location whereas partisanship is measured among residents. with smaller geographies, it becomes increasingly likely that visitors to a poi come from a different home geography, resulting in mismatch between visits and partisanship. a key issue with the safegraph social distancing data is sample attrition. safegraph restricts the panel to devices with observed location pings in a given time period. for some applications, the frequency of location pings depends on device mobility. if devices are immobile at home or turned off, they may not generate location pings and would then be dropped from the sample. the total number of active devices changes over our sample period in a manner consistent with sample attrition. given these issues, we prefer measures of social distancing derived solely from external activity (e.g., poi visits) that do not contain the same measurement error problems. we attempt to correct for the differential attrition in our measure of the share of devices leaving home (see appendix figure a footnotes for correction). where i y is the number of standard deviations above the mean for response i, i  is the continuous measure of republican party lean from to , i x are demographic and location controls, and i  is an error term. figure shows consistent evidence for partisan differences in social distancing, both with and without control variables. on average, participants report reducing contact by . percent, with a sd of . percent. after including controls, strong democrats report engaging in . sd more contact reduction than strong republicans. this corresponds to a gap in contact reduction of . percent for strong democrats versus . percent for strong republicans. similarly, democrats find it significantly more important to stay inside to prevent the spread of the virus versus go outside to help the economy, and the difference between strong partisans is . sd. we then examine the partisan differences in underlying beliefs regarding covid- severity and efficacy of social distancing. we find that democrats' belief regarding the probability of catching covid- without any social distancing is higher than the analogous belief held by republicans. on average, participants assess this probability to be . percent (sd . percent). strong democrats believe this probability is . percent, which is . sd larger than the . percent belief held by strong republicans. we next consider beliefs about future covid- cases in the entire us. we tell participants the number of cases by march and ask them to predict the number of cases in april. on average, participants predict , new cases in april (sd , cases, due to a long right tail). strong democrats predict , future cases on average, which is . sd more than the , predicted by strong republicans. bullock et al. ( ) and prior et al. ( ) show that partisan differences on factual questions often shrink under incentives due to "partisan cheerleading" rather than differences in true beliefs. when we randomize whether subjects' predictions are incentivized for accuracy, we do not find evidence that the partisan gap decreases. this supports the view that democrats and republicans genuinely differ in their beliefs about the severity of covid- . appendix figure a shows that on an explicitly political question, incentives do significantly reduce the partisan gap, consistent with previous findings. appendix figure a shows that comparing individuals within the same county produces qualitatively similar results, complementing the county-level partisan gap observed in the gps analysis. however, since . percent of participants are the only participant from their county, statistical precision is lower and low-population counties are underweighted. finally, we do a back-of-the-envelope estimation of the deadweight loss from equation ( ). we assume that agents have the same quadratic flow utility functions what happens when partisan perceptions differ about infectiousness  . from our survey, we find that the median participant's willingness-to-accept for "cutting off all in-person contact with people outside your household for one month" versus "following your normal routine" (i.e., one month of = c instead of = c ) is $ . from the survey data above, we approximate that democrats reduce consumption by . percent and republicans reduce by . percent. this difference implies that, after controlling for observables that measure private costs and benefits of social distancing, democrats perceive that the expected utility loss from following normal routines instead of cutting off all contact is = $ tr td   %% per month higher than what republicans perceive. plugging the perceived utility loss estimates into equation ( ) if republicans and democrats disagree about the potential risks, they may also differ in how much they reduce the risk of disease transmission through social distancing and other actions. in this case, our model shows how society ends up with more disease transmission at higher economic cost than if people had the same beliefs. our empirical results show that partisan gaps in beliefs and behavior are real. gps evidence reveals significant partisan gaps in actual social distancing behaviors. survey evidence shows substantial gaps between republicans and democrats in beliefs about the severity of covid- and the importance of social distancing. the raw partisan differences partly reflect the fact that democrats are more likely to live in the dense, urban areas hardest hit by the crisis, and to be subject to policy restrictions-in other words, to face stronger individual incentives for social distancing. even after controlling carefully for such factors, however, the partisan gaps remain statistically and economically significant. one explanation for these results is that media sources have sent divergent messages about the coronavirus. appendix figure a shows that the partisan gaps in the survey data are smaller when the partisanship of news consumption is controlled for, and that news partisanship is statistically significantly correlated with beliefs even when party is controlled for. while our evidence does not permit us to pin down the ultimate causes of partisan divergence, these patterns are consistent with divergent messaging playing an important role in driving differences in beliefs and behavior. we use the willingness-to-accept data to say that panel d shades us counties by the effective start date for the earliest "stay-at-home" order issued (see section for sources). blue shading indicates an earlier order, while red shading indicates that an order was issued later or was never issued. note: panel a shows the number of visits (normalized to one) to safegraph pois for each week since january , for republican counties and democratic counties separately. panel b is analogous but plots cumulative, end-of-week values for confirmed covid- cases (per , people) and confirmed covid- deaths (per , , people). republican counties are defined to be those whose republican vote share is greater than the median vote share ( . percent) across the counties in our sample. counties covering new york city, kansas city, and alaska are excluded from these counts, as noted in appendix a. . . negative estimates indicate less concern about covid- or social distancing. demographic controls are age, race, income, education, number of children, log population at the zip code level, county-level deaths and cases, and state fixed effects. percent of observations are set to the mean due to an invalid zip code. self-reported social distancing is the percent reduction in contact with others over one month; effectiveness of distancing is the estimated likelihood of catching covid- in one month without social distancing; importance of distancing vs. economy is subjects' perception of whether it is more important to go out and stimulate the economy versus staying in and preventing the spread of covid- ; predicted cases are predictions about the number of new covid- cases in the us in april; incentivized subjects restrict to the subsample whose answers are incentivized. observations are weighted to mimic a representative sample as described in the text. error bars represent percent confidence intervals. . we begin by matching safegraph pois to the counties in which they are located. we use latitude and longitude from safegraph's july core poi dataset, along with the tiger county shapefile. we successfully assign . percent of the pois to a county. . we then merge the poi-county mapping from ( ) onto safegraph's patterns data using the safegraph-place-id variable. we sum visits by county for a given day, aggregating across pois. . we then merge alternative county-day measures of social distancing onto the output from ( ) . these measures are constructed as follows from the daily social distancing safegraph data with observations at the census block group-day level for january through july . we exclude alaska. we restrict our sample to census block groups with active devices throughout the entire time period. we also drop one census block group with anomalous behavior as notified by safegraph (fips: ) . we aggregate this series to the county level. countable variables (e.g., 'device count') are summed, while we take a 'device count' weighted average of other variables (e.g., 'median home dwell time'). . we then merge gridmet weather data onto the output from ( ). precipitation and temperature means for a given county day are taken as a mean across grid cell points that lie within a county boundary. weather data was not available for hawaii, so this particular state is dropped in regressions including weather controls. . we then merge the new york times covid- tracking data onto our output from ( ). we assume zero cases and deaths for the observations not observed in the new york times data. we drop the five counties associated with new york city and the four counties which overlap with kansas city (mo), because the new york times lists these as geographic exceptions where it either does not assign cases to these counties or excludes cases occurring within the city. . we then merge a dataset of county-level shelter-in-place order start dates onto the output from ( ) and construct an indicator for whether a county had been subject to a shelter-in-place order by a given date. this dataset of shelter-in-place orders is the same as in allcott et al. ( ) , where its construction is described in detail. it is ultimately sourced from keystone strategy, a crowdsourcing effort from stanford university and the university of virginia, hikma health, and the new york times. . we then aggregate the output from ( ) to the county-week level using sums, averages, or start-or end-of-week observations as appropriate. . we then merge onto the output from ( ) a dataset of county-level demographic information constructed as follows. we use the open census data from safegraph, aggregating up the data given at the census block group level to the county level. we combine this with data on county presidential votes shares (mit election data and science lab ). we define the republican vote share to be the share of votes received by the republican candidate over the sum of votes across all candidates. we exclude counties without valid vote data, which drops alaska and two additional counties (fips: , ) . . we begin by matching safegraph pois to the precincts in which they are located. we start with the pois successfully matched in the poi-county mapping from ( ) in section a. . . we use poi latitude and longitude along with precinct-level shapefiles (voting and election science team ). of these pois, we successfully match . percent to a unique precinct in the states covered by these precinct shapefiles and drop the . percent matched to two precincts. the precinct shapefiles cover the following states: ak, ar, az, ca, co, dc, de, fl, ga, hi, ia, id, il, ks, ky, la, ma, md, me, mi, mn, mo, mt, nc, nd, ne, nh, nm, nv, ok, or, ri, sc, sd, tn, tx, ut, va, vt, wa, wi, and wy. . we merge the output from ( ) with the patterns dataset from safegraph using the safegraph-place-id variable. we sum visits by precinct in a given week, aggregating across pois. . we then merge alternative precinct-day measures of social distancing onto the output from ( ) . we start with the cleaned census block group level measures produced from ( ) in section a. . . we then aggregate our (countable) alternative social distancing variables to the precinct level as follows. we do this by first constructing the geographic intersections formed by our precinct shapefiles and tiger census block group shapefiles. let p a , b a , and bp a denote the area of precinct p, census block group b, and of their intersection respectively. for a given count variable b x given at the block group level, we construct a precinct-level estimate as: . we then form ratios (e.g., 'share leaving home') using these summed precinct-level estimates as needed. . we then merge gridmet weather data onto the output from ( ). weather data by precinct day was constructed as a land area weighted average of weather data for overlapping census block groups. census block group centroids were first associated with the nearest grid cell centroid in gridmet. weather data was not available for hawaii, so this particular state is dropped in regressions including weather controls. . we then merge the new york times covid- county-level tracking data onto our output from ( ) . precincts were first associated with the county corresponding to the census block group of their largest intersection. we drop the five counties associated with new york city and the four counties which overlap with kansas city (mo), because the new york times lists these as geographic exceptions where it either does not assign cases to these counties or excludes cases occurring within the city. . we then merge the dataset of county-level shelter-in-place order start dates from ( ) in section a. . onto the output from ( ) . we construct an indicator for whether a county had been subject to a shelter-in-place order by a given date. . we then aggregate the output from ( ) to the precinct-week level using sums, averages, or start-or end-of-week observations as appropriate. . we then merge onto the output from ( ) a dataset of precinct-level demographic information constructed as follows. we start with the open census census block group level demographics from ( ) in section a. . . we then aggregate countable variables to the precinct-level using the intersection share procedure described in ( ). we then form ratios (e.g., 'population density' or 'share hispanic') using these summed precinct-level estimates. we then merge precinct-level presidential votes shares (voting and election science team ) onto the resulting output, constructed as in a. . step ( ). we drop alaska in order to be consistent with our county construction. downloaded from ftp://ftp .census.gov/geo/tiger/tiger /bg/ on april , . this estimate is exactly correct if a given demographic b x is evenly distributed across a census block group's area. • what race/ethnicity best describes you? [american indian or alaska native; asian or pacific islander; black or african american (not hispanic or latinx); hispanic or latinx; white (not hispanic or latinx); other] • do you consider yourself a republican, a democrat, or an independent? [democrat (strongly democratic); democrat (weakly democratic); independent (lean toward the democratic party); independent (do not lean towards either party); independent (lean toward the republican party); republican (weakly republican); republican (strongly republican); other / prefer not to say] • you are invited to participate in an online research study on your views about the news and predictions of what will happen in the future. this is a research project being conducted by researchers at harvard university and new york university. time involvement: your participation will take approximately minutes, and the entire study will take place online. we will ensure that your individual responses are strictly confidential, and research results will only be presented in the aggregate. your responses will not be shared with government officials or any rd party. we hope that the knowledge gained from this study will benefit society in general. we cannot and do not guarantee or promise that you will receive any direct benefits from this study. payments: if you are eligible for the study, and once you complete the study, you will receive a participation fee. you may also earn a bonus payment of up to $ via an amazon gift card. all payments will be through your research provider. participant's rights: if you have read this form and have decided to participate in this project, please understand your participation is voluntary and you have the right to withdraw your consent or discontinue participation at any time without penalty or loss of benefits to which you are otherwise entitled. the alternative is not to participate. you have the right to refuse to answer particular questions. the results of this research study may be presented at scientific or professional meetings or published in scientific journals. contact information: questions: if you have any questions, concerns or complaints about this research, its procedures, risks and benefits, contact the researchers at rb @nyu.edu. independent contact: if you are not satisfied with how this study is being conducted, or if you have any concerns, complaints, or general questions about the research or your rights as a participant, please contact the harvard university area institutional review board (irb) to speak to someone independent of the research team at cuhs@harvard.edu, ( )- - . you can also write to the committee on the use of human subjects, harvard university, -r brattle street, suite , cambridge, ma . please retain a copy of this form for your records. if you wish to participate in this study, please click "i consent" to proceed. this serves as an electronic signature indicating your consent to participate in the study. [i consent; i do not consent] [only consenting subjects proceed] • how many children under the age of do you have? [ ; ; ; ; ; or more] • what is the highest degree or level of schooling that you have completed? [less than a high school diploma; high school diploma or equivalent (for example: ged); some college but no degree; associate's degree; bachelor's degree; graduate degree (for example: ma, mba, jd, phd)] • what was your total income in ? please include only employment income (wages, salary, bonuses, tips, and any income from your own businesses). [i did not earn income in ; $ to $ , ; ...; $ , to $ , ; $ , to $ , ; $ , to $ , ; $ , to $ , ; $ , to $ , ; $ , • think about the ways you may have changed your daily routine in the past two weeks specifically because of the coronavirus. for example, you may be washing your hands more, avoiding restaurants and other public places, and/or reducing interactions with friends and family. • by what percent have you reduced your overall contact with other people as a result of the coronavirus outbreak? please enter a percentage from to . • think back to two weeks ago. • as of two weeks ago, by what percent had you reduced your overall contact with other people as a result of the coronavirus outbreak? please enter a percentage from to . • imagine that starting today and for the rest of the month, you went back to your normal daily routine from before the coronavirus. what do you think is the probability that you would catch the coronavirus in the next month? please enter a percentage from to . [subjects who answer for the percent reduction question see "continued with" instead of "went back to."] • imagine that starting today and for the next month, you cut off all in-person contact with people outside your household. what do you think is the probability that you would catch the coronavirus in the next month? please enter a percentage from to . • we'd like to quantify the overall costs (in terms of time, money, and inconvenience) that social distancing imposes on you. consider a hypothetical situation in a normal month in the future, after the coronavirus outbreak is completely over. imagine you had a choice between: (a) following your normal routine for one month, or (b) cutting off all in-person contact with people outside your household for one month, and receiving $x cash. presumably if you were offered a large amount of cash ($x is large), you'd be willing to cut off all social contact. if you weren't offered any cash ($x is ), you'd prefer to stick with your normal routine. what value of x would make you equally happy with these two options? please j o u r n a l p r e -p r o o f answer in dollars. • when there was no "stay-at-home" order for your area, what did you think was the best way to help the country in this time of crisis? [ -point scale from "go out more to help the economy" to "go out less to avoid spreading the coronavirus"] predictions [if unincentivized:] • you will now be asked to make a few predictions. [if incentivized:] • you will now be asked to make a few predictions. think carefully! we'll randomly select participants for an accuracy reward. if you're selected, we'll pay you up to $ depending on how accurate your prediction was. for example: -if your answer is exactly right, we'll give you $ -if your answer is % off, we'll give you $ -if your answer is % off, we'll give you $ -... -if your answer is % off, we'll give you $ -etc. all subjects see: • we want to know how well you think the u.s. will limit the spread of the coronavirus in the next month. there had been , known cases of coronavirus in the u.s. by march . how many additional known cases will there be in the u.s. in the month of april? • realclearpolitics reports polling data on public approval of president trump's handling of the coronavirus outbreak. what percent of people will say they approve of trump's handling of the coronavirus outbreak on the latest poll that ends before april ? j o u r n a l p r e -p r o o f journal pre-proof appendix figure a : poi visits in note: figure shows the aggregate number of poi visits (normalized to one) for weeks starting on january , for republican counties and democratic counties. republican counties are defined to be those whose republican vote share is greater than the median vote share ( . %) across the counties in our sample. counties covering new york city, kansas city, and alaska are excluded from these counts, as in figure and as noted in section a. . . appendix figure • panel a: the first plot drops the health controls; the second plot drops the economic controls; and the third plot drops the weather controls. • panel b: the first plot drops state-time fixed effects (keeping county fixed effects and time fixed effects); the second plot interacts time fixed effects with linear versions of all controls, rather than with decile indicators; the third plot adds the following controls, each with time-varying decile indicators: share under age ; shares with degrees in science+engineering, business, or arts+humanities; share of households with at least one vehicle; share of homes rented; share speaking only english at home; share with health insurance; shares commuting by auto, taxi, cycle, walking, or without commute; share enrolled in grad+professional school; share citizens; share married; shared of households with an age + occupant; shares of households of size , , or - ; share of households which are a family. this third plot also adds as a control the log of poi visits (plus one) in the same week and county but during the previous year, included as a linear control interacted with time fixed effects. • panel d: the first plot only keeps counties with a population above , (dropping . percent of counties in our sample); the second plot only keeps counties with a population below , (dropping . percent of counties in our sample); the third plot drops california, washington, and new york. • panel e: the first plot drops counties for which the republican vote share was in the bottom or top decile; the second plot keeps counties for which the republican vote share is greater than the median; and the third plot keeps counties for which the republican vote share is less than or equal to the median. negative estimates indicate less concern about covid- or social distancing. demographic controls are age, race, income, education, number of children, log population at the zip code level, and county fixed effects. . percent of observations are dropped due to an invalid zip code or unique county. the remaining observations are weighted to mimic a representative sample as described in the text. self-reported social distancing is the percent reduction in contact with others over one month; effectiveness of distancing is the estimated likelihood of catching covid- in one month without social distancing; importance of distancing vs. economy is subjects' perception of whether it is more important to go out and stimulate the economy versus staying in and preventing the spread of covid- ; predicted cases are predictions about the number of new covid- cases in the us in april; incentivized subjects restrict to the subsample whose answers are incentivized. error bars represent percent confidence intervals. appendix figure a : differences in beliefs and actions by party and news consumption note: figure shows coefficient plots of regressing normalized measures of beliefs and actions on coronavirus news consumption and our our seven-point measure of partisan affiliation which ranges between (strongly democratic) and (strongly republican). negative estimates indicate less concern about covid- or social distancing. news consumption weights respondents' ratings to "how frequently are you getting news and information from each of the following sources about the coronavirus?" as specified in the survey details of the appendix. all coefficients include demographic controls of age, race, income, education, number of children, log population density at the zip code level, and state fixed effects. percent of observations are set to the mean due to an invalid zip code. for each outcome, the top plot does not control for news, the middle plot linearly controls for news, and the bottom plot shows the coefficient on news in the middle specification. self-reported social distancing is the percent reduction in contact with others over one month; effectiveness of distancing is the estimated likelihood of catching covid- in one month without social distancing; importance of distancing vs. economy is subjects' perception of whether it is more important to go out and stimulate the economy versus staying in and preventing the spread of covid- ; predicted cases are predictions about the number of new covid- cases in the u.s. in april; incentivized subjects restrict to the subsample whose answers are incentivized. observations are weighted to mimic a representative sample as described in the text. error bars represent percent confidence intervals. development of gridded surface meteorological data for ecological applications and modelling a new poll shows a startling partisan divide on the dangers of the coronavirus the effect of stay-at-home orders on mobility, economic, and health outcomes during the coronavirus pandemic early evidence on social distancing in response to covid- in the united states yotam margalit, and matteo pinna. . the effect of fox news on health behavior during covid- experienced segregation coronavirus city and county non-pharmaceutical intervention rollout date dataset michaela pagel, constantine yannelis. forthcoming. how does household spending respond to an epidemic? consumption during the covid- pandemic risk perception through the lens of politics in the time of the covid- pandemic beyond the running tally: partisan bias in political perceptions the stunning contrast between biden and trump on coronavirus political determinants of population health covid- us county policies, hikma health political beliefs affect compliance with covid- social distancing orders forthcoming. political cycles and stock returns tracking public opinion on the coronavirus. morning consult you cannot be serious: the impact of accuracy incentives on partisan bias in reports of economic perceptions madhav marathe, and michael bernstein. crowdsourced covid- intervention data americans step up their social distancing even further who participated in the aca? gains in insurance coverage by political partisanship the role of fear-related behaviors in the - west africa ebola virus disease outbreak the persuasive effect of fox news: non-compliance with social distancing during the covid- pandemic as virus takes hold, resistance to stay-at-home orders remains widespread -exposing political and social rifts associations between population based voting trends during the us presidential election and adolescent vaccination rates data we clean the survey data from qualtrics as follows: . we match participant ids from qualtrics with a list of emailed ids from cloudresearch and drop observations that do not match to remove test subjects. there is one exception, where the id on qualtrics did not correctly generate. we find exactly one remaining participant with the same demographics in the cloudresearch, so we keep this participant. . we change one miscoded age from . to and one miscoded zip code from we match zip codes to counties and use the week of march -april and get county-level covid cases and deaths via the new york times. all zip codes in new york city are matched to the city-level cases and deaths since county-level data is unavailable from the new york times. for analyses, we control for log we weight observations across age category, gender, race/ethnicity, and party affiliation using the stata ebalance command ) cnn; ( ) facebook; ( ) fox news; ( ) msnbc for our news consumption specification, we use the question on consumption of news about the coronavirus. often is coded as , sometimes as / , rarely as / , and never/not familiar as . answers are then multiplied by the pre-specified partisanship of each source (- for nyt; the following demographic groups prior to weighting: • age: % asian or pacific islander, . % other. • party: . % democratic, . % republican, . % independent, . % other a. . survey questions screening • what is your gender? figure a for county-and precinct-level regressions respectively, except that we replace log visits with the following alternative outcomes:• panel a: 'log devices leaving home' is the log of one plus the number of active devices in the panel minus the active devices never observed leaving their geohash- home. 'log stops in non-home cbgs' counts, by home county, the number of devices which stop in a given non-home census block group. we then sum across non-home census block groups and days to form our county-week outcome. 'log median time away from home' calculates the median time a device is observed outside its geohash- home, by home census block group. we then take a device-weighted average across census block groups and days to form our county-week measure, and then take the log of this value. negative values indicate less concern about covid- or social distancing. demographic controls are age, race, income, education, number of children, zip code logged population density, county-level deaths and cases, and state fixed effects. percent of observations are set to the mean due to an invalid zip code. self-reported social distancing is the percent reduction in contact with others over one month; effectiveness of distancing is the estimated likelihood of catching covid- in one month without social distancing; importance of distancing vs. economy is subjects' perception of whether it is more important to go out and stimulate the economy versus staying in and preventing the spread of covid- ; predicted cases are predictions about the number of new covid- cases in the u.s. in april; incentivized subjects restrict to the subsample whose answers are incentivized. error bars represent percent confidence intervals.appendix figure a : effect of incentives on beliefs note: figure shows coefficient plots of regressing beliefs on republican party lean, with and without incentives for getting close to the correct answer. trump disapproval is a low-stakes question that is susceptible to partisan cheerleading (bullock et al. ; prior et al. ) . these results show that predicting covid- cases does not appear susceptible to the same behavior. observations are weighted to mimic a representative sample as described in the text. error bars represent percent confidence intervals.appendix figure a : partisan differences in beliefs and actions: county fixed effects j o u r n a l p r e -p r o o f key: cord- -qeuvymu authors: banai, reza title: pandemic and the planning of resilient cities and regions date: - - journal: cities doi: . /j.cities. . sha: doc_id: cord_uid: qeuvymu the emergence of the coronavirus pandemic motivated this paper, which revisits the nexus of public health and the city, itself a main source of a pandemic which similarly threatens the lives and properties of the world population gradually one glacier at a time: climate change. we argue that pandemics expose both the vulnerability and resilience of the urban system expansively, from rooftop to the region, but also serve as change agents for the planning of resilient cities and regions globally. the discussion of the urban system and the pandemic is comparative, with the recent coronavirus and climate change, a persistent, long-lasting pandemic. the historical and critical review and synthesis of the durable concepts of the urban system at the kernel of the theories and practices of urbanism is highlighted by place matters, cyberspace, density, access, and the city-region. we note the implications for reconfiguring the resilient urban system of the future effectively with pandemic as change agent and the comprehensive plan and its regulatory zoning ordinance as implementation tool. public health and city planning have common disciplinary purposes. city planning's professional identity is defined as a guardian of "public interest." standard city planning enabling act (scpea, u.s. department of commerce ) is even more specific, defining municipal planning's promotion of "health, safety, and general welfare" of the population. public health is about identification, control, and prevention of disease. the common references to parks and open spaces with a physiological metaphor-the "lungs" of the city-connotes the nexus of public health and the city explicitly. city planning's focus is the physical layout of the city in a manner that promotes health and prevents the occurrence of diseases in the first place. concomitantly, city and regional planning and design theories, concepts, regulations, and practices emerge historically in response to public health crises, including pandemics, pollution with rapid industrialization, congestion with urbanization, and loss of green space in cities. the origin of modern city planning is aligned with sanitary, housing, and social reforms since the mid-nineteenth century and around the turn of the twentieth century-movements dealing with inadequate sanitation-itself a pandemic response-and limited access to air and sunlight in crowded tenement housing and dilapidated slums. the coronavirus pandemic has at least temporarily significantly reconfigured city life-the relation of work and residence, and leisure, use of public space, safety and security of transportation, both public and private-and posed fundamental equity of access to resources. a smart planning scenario could not have anticipated and illustrated the wide-ranging, impactful socio-spatial dimensions of the coronavirus pandemic in entirety this vividly, let alone applied standard urban planning tools-the comprehensive plan and zoning regulations-proactively (banai, a; kelly, ) . it turns out, planning's tool set are disproportionately limited piecemeal or disjointed compared to the magnitude and wide-ranging scope of the better known, durable pandemic of climate change. however, the global experience of the coronavirus pandemic also informs and suggests what kind of planning is commensurate with the dimensions of the challenges posed by climate change. it turns out, pandemics expose the vulnerability and resilience of the urban system, ironically with durable concepts of urbanism, highlighted from the rooftop to the region. the paper is organized by a discussion of durable concepts of urbanism, with implications for reconfiguring the urban system, aided by invoking urban planning's standard tool-the comprehensive plan. the paper concludes with a discussion of planning resilient urban form of the future in the era of climate change. oxford dictionary defines pandemic with its greek origin in midseventeenth century, pandēmos, all (pan) people (demos) "prevalent over a whole country or the world." arguably, climate change, which is prevalent globally, fits that definition, just as coronavirus does. a question is immediately raised: which pandemic is more costly-coronavirus or climate change? hint: one pandemic is a one-hundred-year event, compared to the other, with an incubation period that started with the industrial revolution in s. however, the two pandemics have a similar pattern of spread: exponential. measured by loss of human life, unemployment, underemployment, social isolation, public expenditures, reduction in gross domestic product, and supply-chain interruption, the costs of coronavirus are immense. however, compare the cost of climate change. green house gas (ghg) traps pollutants in cities. combine tailpipe and smokestack pollution from vehicles, buildings, factories, and heat islands in cities, and there is recipe for respiratory illness, including asthma and cardiovascular disease, consequential for the children, the elderly, and populations predisposed with genetic chronic health conditions. parenthetically, people with respiratory and cardiovascular illness and diabetics, which are also linked to urban form-induced obesity as well as poor diet, have a lower chance of surviving the other pandemic: coronavirus. furthermore, consider the costs of entire islands inundated due to sea-level rise, or so-called king (or high) tides that infiltrate coastal cities' groundwater table with sea salt, threatening drinking water or causing frequent surficial flooding depositing sewage into rivers and lakes (chicago), and disrupting traffic in city streets (miami). add the mitigation costs of levee, dike, and sea-wall construction in coastal cities globally, like new york city, new orleans, amsterdam, venice, and london. include droughts that threaten agriculture, causing food insecurity that subsequently threatens employment and national security (even a source of failing states), and induces population migration in search of survival. this is not an exhaustive itemized costs brought about by the silent pandemic of climate change gradually taking its toll on the built and natural environments. the evidence of climate change pandemic and its consequences for cities and regions is compelling. the itemized list in the comparison of pandemics of climate change vs. coronavirus is tentative with respect to consequences of coronavirus. the juxtaposition of the two pandemics, however, is instructive. ironically, one pandemic has a positive impact on the other (see fig. ). images in the media show clearer skylines and iconic, ground-level landmarks, such as the eiffel tower, to be more visible than usual due to quarantines in otherwise congested, polluted, populated, heated-up cities. there are even the images of venice's canals and waterways looking clearer than ever, as the coronavirus quarantine leaves them undisturbed. u.s. environmental legislation has ensured public health of the city with clean air and clean water for the past half-century, abating ghgs-carbon dioxide, sulfur dioxide, nitrate dioxide. similarly, clean water legislation regulated the disposal of cities' waste into rivers, the sources of drinking water and aquatic life. ohio's cuyahoga river was once so polluted that it caught fire, but owing to the clean water act, it's now home to marine life. however, the images of clean waterways and clear skylines during the coronavirus epidemic suggests next steps toward further management of waterways and air pollution in cities. we hope for a vaccine that will cure the coronavirus, but no such thing can solve the pandemic of climate change. it takes more than a shot in the arm. surreal images of cities known for their population density, air pollution, and traffic during the pandemic appeared in the media-skyline visibility but with empty streets, deserted downtowns, blighted parking lots surrounding commercial retail stores, empty office buildings, locked college and university gates, and desolate public parks. in the pre-coronavirus era, empty stores and parking lots and desolate public spaces were regarded as indicators of intolerable blight, justification for urban revitalization. ironically, among the vestiges of blight and sprawl is the drive-in movie theatre, revived because of the pandemic as a safer alternative than the big-box movie theatre. and the impact of social isolation on mental health is also recognized. how could cities and regions sustain the public health benefits of cleaner air and water with a resilient urban form and a smaller ecological footprint post-coronavirus? the coronavirus pandemic, despite its devastatingly inimical tolls on humans, sheds light on the architecture of urbanism, revealing strengths and vulnerabilities of the urban system. the pandemic has in effect enabled a social experiment with controls that are usually possible only in the closed system of a laboratory, not in the open system of a society; however, this experiment calls for a rethinking the urban system with expansive concepts of resilience in planning cities and regions. we note the implications for the comprehensive plan in the face of climate change. the literature on the importance of place, and the related discussion of place-making in urban studies abound. much of the discourse of the new urbanism which emerged in the s is about civic places, which disappeared in the private, subdivided spaces of suburbia (katz, ) . the american dream of a house, a yard, and car excluded community, as hayden ( ) argued (see also calthorpe, ; mcharg, mcharg, / . the mainly residential suburbs bereft of civic spaces could not accommodate a social place for the teenage population without the car, with the exception of vacant lots and buildings under construction. suburbia segregated commercial-residential-public land use, in contradistinction to the historic american main street with fine-grained, mixed land use, and an accessible park. the comprehensive (master) design plans of new urbanism aimed to remedy this shortcoming with integrated land use and pedestrian-friendly access, with enhanced public realm elements, which occupy prominent landmark locations with water feature and articulated surficial materials of the sidewalks anchored by gazebos and pocket parks, heeding the pedestrian as well as vehicular circulation. when the pandemic limited or prohibited access to the public realm, its significance became even more apparent, albeit with an eerie sense of a public realm that is no longer a public domain. the longing for the city's public realm, temporarily off-limits during the pandemic, was expressed through the building balcony, which architecturally transitions between public and private space. the balcony substituted for an inaccessible public realm-from the street, the town square, the park, the waterfront, the cemetery, to places for religious gatherings, church, synagogue, mosque-places that functioned, albeit with some adaptation, aided in cyberspace, and occasionally in defiance of any imposition of control (see also oldenburg's ( oldenburg's ( / ) notion of the necessity of "the third place" where essential human interaction occurs beyond work and home; see also calthorpe & fulton's, , page elaboration). the limit of the experience of physical place via cyberspace is readily revealed if reminded by lynch's ( ) cognitive mapping of the five elements that makes the city legible or imageable, and the sense of place attributes including ambience, sound, smell, topography (steepness of roads) and the like. if eclipsed in dense theoretical academic writing, commercial and social media alike exemplified the significance, actual experience of and the longing for the city's public realm, particularly during a pandemic. the vitality of the city is determined by place. where else? vitality is among the five "performance dimensions" of good city form, defined by lynch ( , page ) as "… the degree to which the form of the settlement supports the vital functions, the biological requirements and capabilities of human beings-above all, how it protects the survival of the species." (see also banai & rapino, .) where better to observe the function (or dysfunction) of the settlement form but in the city's public realm, particularly in a pandemic. it is not just the pandemic of an infectious disease that is consequential for the vitality of the city's public realm. climate change's extreme weather pattern with heavy rain events threatens city's vital public realm element with street flooding. the point-and non-pointsource pollution during intense rain events threatens city's water bodies. the comprehensive plan can increase cities' resilience by rezoning blighted, abandoned industrial and commercial properties as green open space buffers that absorb or slow surficial runoff that creates hot spots of pollutants in cities' rivers, creeks, and streams. a dominant element of the public realm is the suburban arterial street. the wide arterial street is enhanced if "shared" equitably accommodating movement of pedestrians and vehicles. the long-term comprehensive plan is a tool to accomplish this aim, by physical design alterations that "calm" traffic and thereby increase public safety. integration of green space in the arterial street in the form of medians or embankments enhances pedestrian safety while abating runoff during the intense rain events that characterize climate change. telecommunications technology and cyberspace substitutes for risky in-person communication in physical space during an easily transmittable pandemic. communication theorists widely touted the benefits of interaction at a distance even pre-coronavirus. among others, webber ( ) argued the case for "community without propinquity." the coronavirus effectively revived and reminded us of the merits of the arguments for and against more widespread online communication. arguments in favor of communities of place rather than communities of interest in cyberspace (calthorpe & fulton, ) , however, suggest plausibility with the experience of communication during pandemic and the longing for interaction in physical space of place and neighborhood, and the (physical) public realm, even in defiance of state control. economic and urban theorists up the ante by privileging the benefits of interaction with economies of agglomeration in physical space necessary for efficient business transaction (see also lynch ) . notwithstanding the facility of communication in cyberspace, still an urban form of the future-the aerotropolis-is defined by a physical space that accommodates agglomeration of firms and business transactions in a central location akin to the city's central business district (cbd) (kasarda, , kasarda, , kasarda and lindsay . the pandemic showed us the inequity of access due to lack of broadband technology-the digital divide-so the comprehensive plan is an ideal tool for enhancing city's resilience by a planning infrastructure that not only includes water, sewer, and roads, but also broadband service (see also kelly, ) . we learned from the pandemic how vital functions are interrupted-education, from pre-school to college; health care; and access to jobs and services. broadband access is not a luxury but a necessity when in-person access is interrupted or not an option. parenthetically, a similar logic holds in planning transit-supportive or transit-oriented developments. the urban form, with its land-use mix and proximity to the centrally located retail and office services are desirable features because of walkability, regardless of the availability of transit (calthorpe, ; calthorpe & fulton, ). the environment-behavior nexus was investigated more than half a century ago by the then-burgeoning subfield of environmental psychology. these well-known laboratory experiments revealed how rats develop abnormal behavior when subjected to crowding. concomitantly, the classic environmental-behavior studies informed how urban form likely impacts the physical and mental health of the urbanists. even obesity (body-mass index) is linked to urban form (walkability), elucidated in the contrast of compact vs. urban sprawl (e.g., frumkin et al., ; ewing et al., ) . commentators, backed by empirical evidence, touted the public health benefits of cities that promoted walkability with multi-modal regional mobility, thereby abating obesity, and which contained places of work as well as residence and leisure, thereby minimizing stressful commuting to work. (ewing et al., ; frumkin et al., ) . the urban-studies literature has given considerable attention to density. density figures prominently in urban studies since the feasibility of a vital element of urban form-public transit-is contingent on population density's minimum threshold. however, even predating the laboratory experiments of the environmental psychologists, an english thinker (howard, (howard, / around the turn of the century proposed and later constructed a garden city that meant to address the health, safety, and general welfare of industrial city residents exposed to all the negative consequences of industrialization, crowding, congestion, pollution, sprawl, and lack of parks and open green space. arguably, the small, low-density garden city land use in balance with the natural environment is a more resilient model of urbanism than the compact, high-density new york city in the face of epidemic guidelines that call for social distancing and low population density of the public realm. durable concepts of urbanism originate prominently in the contrast of two prominent thinkers, one english and the other french. the french modernist architect-urbanist le corbusier ( corbusier ( / ) touted his tower-in-the-park skyscraper concept of contemporary city as a better solution to the rapid urbanization of population and congestion spurred by industrialization. the contemporary city accommodated times the population of the garden city with only , that his english predecessor, howard ( howard ( / had proposed in skyscrapers (legates & stout, ) . the "popular response" to plan voisin, a later version of the contemporary city proposed for central paris in , was "outrage" (legates & stout, ; see also birch, ). however, corbusier's concept of a dense, modern urbanism with the iconic skyscraper endures globally in cities, famously in the iconic new york city (see lang, ) . the pandemic cast a negative image of urban density, and its corollary, public transportation, as hotspots of the coronavirus (new yok city, los angeles, and compact spanish, italian, and english cities). density figures prominently in contemporary accounts of new urbanism since density correlates with walkablity in the "transit metropolis" (cervero, ) . even before the coronavirus pandemic, the dense high-rise buildings-particularly for public housing in neighborhoods disconnected from the rest of the city-connoted the image of the vulnerability of their impoverished, isolated, low-income residents. the destruction of st louis's pruitt igoe-designed by a renown modernist architect-demonstrated the unsustainability of the high-rise public housing project. in contrast, modern high-rise buildings could densely accommodate residents in resort towns with a premium view and rent. their residents could weather the lock-down, shelter in place guidelines during the pandemic. however, public housing, following federal guidelines like hope vi and choice neighborhood, is now lowrise with a front porch that resembles houses in older american city neighborhoods before the suburbanization of businesses and population spurred by post-war national interstate highway system. however, density is still a hard sell in popular discussions of realestate markets. low-density single family rather than multi-family housing is politically palatable to politicians who count votes with rooftops, even though compact land development is arguably environmentally more sustainable particularly in the face of climate change and demographic shift (immigration) that increase demand for housing and ancillary urban services-water, sewer, and road. in urban-studies literature, discussions of density and how higher thresholds are tolerated, particularly by urbanites accustomed to low-density suburban sprawl, extend to the justification of trade-offs, i.e. how density is plausibly compensated with other factors, (urban) design features that enhance aesthetics of place, and (land-use) diversity that improve proximity of housing to jobs, services, and amenities like parks and open space-so-called ds (for impact on travel, see cervero & kockelman, ) . density correlates with demography. in the context of the pandemic, still other factors must be added to the ds in deference to public health: demography, disaggregated by racial composition, ethnicity, age, and income. the correlations among the factors are instructive. at risk are residents characterized by compact living and commuting, transit-dependent population, or workplace-residence separation exacerbated by the digital divide. for the purposes of public health during the epidemic, the aforementioned factors require optimization simultaneously. the comprehensive city plan is a logical tool for that optimization. let us posit the concept of access inclusively with lynch ( ) as a dimension of the performance of urban form, not merely by modes of travel to work or services, but also availability of resources. perlman and o'meara ( ) remind us that the urban poor are likely located in "ecologically fragile areas of cities," without adequate water and sewers. coronavirus-prevention guidelines include frequent handwashing. how could these hygiene standards be met when there is no access to running water in poor settlements of the global north and south? the navajo settlement is but one example in the u.s. (see also www.digdeep.org). war-stricken regions of the world whose populations are victimized by global power play, such as libya, yemen, syria, turkey, and afghanistan, and refugees in greek islands, are among other examples. once again, pandemics-be they climate change or the coronavirus-reveal the vulnerability of the population in urban, periurban, and rural areas with global inequity of access to the resources fundamental to human survival. the coronavirus pandemic had a positive effect too, with the u.n. directorate's declaration to halt ongoing wars globally, particularly in the middle eastern countries most heavily impacted. the impact of military conflicts on the global population and environment is rarely discussed in the literature of climate change. the advocacy planning argument of the s and s that posed the limit of comprehensive master plans and stressed the necessity of the "plural plan" responsive to the underrepresented, marginalized, disenfranchised, colonized population revives the discussions of the equity of access to resources with environmental justice in the twenty-first century, particularly in the face of pandemics (see davidoff, ) . the wealth of nations is created in cities, jacobs ( ) reminds us. global environmental sustainability starts with urban environmental sustainability (perlman & sheehan, ) . cities provide economies of agglomeration, and of scale with efficiencies of resource utilization. however, the idea of abating pressure on resources concentrated in urban centers, like london and new york, and striking a balance of nature and development by spreading population to the larger region did not stop in england with howard's concept of the garden city, noted above. the garden city idea influenced a group of regionalists, or de-centralists with english connections in new york. a multidisciplinary team, journalist (howard) , socio-cultural critic (mumford), social reformer (bauer), economist (chase), biologist (geddes), sociologist (perry), forester-naturalist (mackaye), a developer (bing), and several architects (ackerman, whitaker, wright and stein) formed the regional plan association of america (rpaa, s; see also banai, banai, , b ). an exemplary feature of this regional planning is its multi-scale scope: from neighborhood to the region. it turns out, the "neighborhood unit" (perry, ) is an enduring concept manifested in new urbanism that emerged in s. cities ( ) the economist member of the regional plan association of america (rpaa s), stuart chase, considered the bigger picture of the efficiency of the urban and regional economy as a problem, stated thus: "the regional planning of communities would wipe out uneconomical national marketing, wipe out city congestion and terminal wastes, balance the power load, take the bulk of coal off the railroads, eliminate the duplication of milk and other deliveries, short circuit such uneconomic practices as hauling pacific apples to new york customers by encouraging local orchards, develop local forest areas and check the haulage of western timber to eastern mills, locate mills near cotton fields, shoe factories near hide producing areas, steel mills within striking distance of ore beds, food manufacturing plants in small giant power units, near farming belts." (quoted in hall, , pp. - ) for further discussions of local vs. global, economic vs. ecologic tensions in urban development, see korten's ( ) political-economic critique of capital markets, deemed as exacerbating ecological systems, shuman's ( ) "replacing imports" in self-reliant local communities in a global age, and roseland and soots' ( ) "strengthening local economies." the break in the global supply chain during the coronavirus pandemic made the dire consequences abundantly clear, particularly for the health-care sector with loss of life. how "uneconomical," chase might ask, is the practice of offshoring industrial and manufacturing production and sending the finished products, in whole or part, back to the country of origin by air, sea, river, rail, and road? parenthetically, airline tickets now relay magnitude of carbon footprint in trans-atlantic passenger flights. for a sustainability assessment of a futuristic concept of urban form anchored by a "globally networked economy's airport"-the aerotropolis-see banai ( ) . air transportation's contribution to global climate change remains awaiting the development of technologies that economically sequester atmospheric carbon. the idea of the city and the region as a unit is at the kernel of how the u.s. census defines the metropolitan region, metropolitan statistical area (msa) determined by commuting (see banai & wakolbinger, ) . parenthetically, this very commuting among inner city and suburban municipalities aids in the transmission of coronavirus, from high-density urban to low-density rural counties. young ( ) quotes the governor of new york, "many people in the new york city metro area live and work across three states' borders, so just as they coordinated shutting down various businesses [during coronavirus], it makes sense to eventually together bring people back." the holistic concept of the metropolitan region that highlights the functional links among urban and regional economies also reveals the strengths and limits of the urban system, and thereby informs the comprehensive city plan's objectives of enhancing sustainability and resilience of the built and natural environments of climate change. human activity's gradual degradation of the natural environment has a long history that has only intensified since the onset of the industrial revolution, with exponential growth in carbon emission due to burning of fossil fuel-coal, oil and natural gas-sources of ghs. a poplar idiom is aptly invoked. the planet earth's holding capacity, like the proverbial camel, is finite, continually burdened with harmful human activity, diminishing gradually by each melting glacier, like straw on a camel's back. (formally, economists use the term "margin," or "last unit" to explain concepts, as in the cost of producing one more unit of a product, the marginal cost of production.) the precise tipping point, or better stated, breaking point for the planet earth beyond any recovery, is in debate. the signs are visible in the built and natural environments, with droughts, fires, floods threatening food security, national security, employment security, rising poverty, inequality, and global diaspora (brown, (brown, , . wackernagel and rees ( ) measure ecological footprint by amount of land needed to sustain human needs for production of food and disposal of waste. land is a finite resource. by that definition, wackernagel and rees ( ) illustrate that if everyone lived like people in the netherlands, then two additional planet earths would be needed. parenthetically, the netherlands example is ironic, given the compact dutch urban form integrated with nature and exemplary sustainability practices (see beatley ) . furthermore, amsterdam's schiphol airport is regarded as a model for the "aerotropolis," a futuristic concept of urban form (kasarda and lindsay ) . there is no literature on the public heath aspects of the aerotropolis; however, comparing it to the exemplary amsterdam metropolitan region that contains the airport (schiphol) offers some clues. the region is characterized by the historic structures, integrated urban development and nature, compact, mixed-land use with multi-modal regional mobility architype of european cities (see beatley, ). european countries with net zero are the ideal of how we should live next. however, pacala and socolow ( ) offer a variety of existing technological solutions that limit carbon emission over the next fifty years(see also calthorpe, ) . the limit is achieved by a combination of alternative sources, from renewable energy (solar, wind, hydro) to conservation to nuclear power. interestingly, in spain, a country hit hard by one pandemic (coronavirus), the road to recovery is through solutions to the other pandemic-climate change-such as pledging to outlaw fossil fuel-coal, oil, natural gas-toward % renewable sources of energy. the pandemic has a global reach, by definition. the method of the approach and presentation of this paper is comparative by juxtaposing the pandemics of climate change and coronavirus, and through a historical and critical review and synthesis of the durable concepts of the urban system at the kernel of the theories and practices of urbanism expansively, from rooftop to the region, highlighted by place matters, cyberspace, density, access, and the city-region. the urban system connotes a holistic approach, with a synthesis of concepts of the urban system elements that are heretofore regarded individually particularly in dealing with resilience. the holistic notion of the urban system thus sheds new light on the resilience of system parts when regarded as a whole. we have juxtaposed the recent coronavirus pandemic with climate change, a persistent, long-lasting pandemic which threatens civilization, not merely urbanization (brown, (brown, , . pandemics expose the vulnerability and resilience of the urban system ironically with durable concepts of urbanism, from rooftop to the region. the recent pandemic has posed the dilemma of physical vs. virtual space. the accounts of this distinction appear with durable concepts of place and space in urban studies, which shed light on recent pandemic-related discussion. cyberspace and physical space are related concepts. the distinction made between "community of place" vs. "community of interest" is revisited in urban studies, particularly with the concepts of placemaking. there are limits and possibilities in both cyberspace and physical spaces. the critical role of access is also posed in both spaces, with respect to efficiency and justice. one space asserts the dilemma of a "digital divide," whereas the other asserts the dilemma of public vs. private transportation with equity and efficiency. place density is also a durable, controversially held concept of urbanism. we have highlighted discussion of density dating from first decades of the twentieth century, relating to the challenges of public health. the recent pandemic posed anew the challenge of public health with urban density. pandemics, while exposing the vulnerabilities of the urban system, are also a driver of positive change in planning resilient urban form of the future. reconfiguring the urban system in the era of climate change is compelling with the majority of world population living in cities and regions. at the outset of the paper (pages - ), we pose the kind of planning that is commensurate with the dimensions of the challenges posed by the pandemic needed for resilient cities. we argue the case for comprehensive planning, and provide specific interventions toward resilience, with place matters, cyberspace, density, access, and the cityregion. the logic of the long-term comprehensive plan is compelling given the interrelated elements of the urban system. the argument is that resilience of the whole is dependent upon the resilience of the individual parts. the paper thus provides specific areas of how the parts are addressed with elements of the urban general or comprehensive plan. for brevity , the discussion of the application of comprehensive planning as a mode to enhance resilient cities is limited. the comprehensive plan with a legal backing is long-term oriented, with parts that account for key physical elements that prepare the urban and regional system to confront the challenges of climate change. the comprehensive plans rarely include physical elements that enhance the urban and regional resilience proactively in the face of climate change. we have identified how the urban system is reconfigured, from the infrastructure of the public realm (the street, town square, park, and open space) to place density with a human-scale, telecommunication, regarded at par with essential infrastructure of water, sewer, and road, to integrated urban and regional economies that enhance efficient, sustainable local production and distribution of resources. further studies fruitfully build on our comparative, evaluative framework of pandemics as drivers of change toward resilient cities of the future. social theory and the region: from the regional planning association of america to the restructuring of socio-spatial theory, with policy implications plan vs project dilemma in urban and regional studies revisited: a progress review of urban and regional studies the metropolitan region: from concepts to indicators of urban sustainability the aerotropolis: urban sustainability perspectives from the regional city urban theory since a theory of good city form ( ): a progress review a measure of regional influence with the analytic network process planning for sustainability in european cities: a review of practices in leading cities planning for sustainability in european cities: a review of practices in leading cities the urban and regional planning reader plan b . : mobilizing to save civilization plan b . : mobilizing to save civilization journey to planet earth the next american metropolis-ecology, community, and the american dream urbanism in the age of climate change the regional city: planning for the end of sprawl transit metropolis: a global inquiry travel demand and the ds: density, diversity, design advocacy and pluralism in planning companion to urban design urban sprawl and public health cities of tomorrow building suburbia, green fields and urban growth to-morrow: a peaceful path to real reform/garden cities of tomorrow cities and the wealth of nations asia's emerging airport cities aerotropolis: the way we'll live next? the new urbanism: toward an architecture of community community planning-an introduction to the comprehensive plan civic engagement in creating future cities urban design: the american experience la ville radieuse (the radiant city) early urban planning - / ). design with nature the great good place: cafes, coffee shops, bookstores, bars, hair salons, and other hangouts at the heart of a community stabilization wedges: solving the climate problem for the next years with current technologies fighting poverty and environmental injustice in cities state of the world the neighborhood unit: a scheme of arrangement for the family-life community. regional study of new york and its environs, vii, neighborhood and community planning, monograph one - strengthening local economies. state of the world : our urban future going local: creating self-reliant communities in a global age our ecological footprint gabriola island the urban place and the non-place urban realm. explorations into urban structure new york will work with new jersey, connecticut to restart economy, cuomo says the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. key: cord- -r k ob authors: raina macintyre, c.; engells, thomas edward; scotch, matthew; heslop, david james; gumel, abba b.; poste, george; chen, xin; herche, wesley; steinhöfel, kathleen; lim, samsung; broom, alex title: converging and emerging threats to health security date: - - journal: environ syst decis doi: . /s - - - sha: doc_id: cord_uid: r k ob advances in biological sciences have outpaced regulatory and legal frameworks for biosecurity. simultaneously, there has been a convergence of scientific disciplines such as synthetic biology, data science, advanced computing and many other technologies, which all have applications in health. for example, advances in cybercrime methods have created ransomware attacks on hospitals, which can cripple health systems and threaten human life. new kinds of biological weapons which fall outside of traditional cold war era thinking can be created synthetically using genetic code. these convergent trajectories are dramatically expanding the repertoire of methods which can be used for benefit or harm. we describe a new risk landscape for which there are few precedents, and where regulation and mitigation are a challenge. rapidly evolving patterns of technology convergence and proliferation of dual-use risks expose inadequate societal preparedness. we outline examples in the areas of biological weapons, antimicrobial resistance, laboratory security and cybersecurity in health care. new challenges in health security such as precision harm in medicine can no longer be addressed within the isolated vertical silo of health, but require cross-disciplinary solutions from other fields. nor can they cannot be managed effectively by individual countries. we outline the case for new cross-disciplinary approaches in risk analysis to an altered risk landscape. few precedents or analytical tools. these technologies are increasingly available to hostile states and non-state terrorist groups. the rapidly evolving landscape of dual-use risks illustrates how societal preparedness for new challenges in health security can no longer be addressed within isolated vertical siloes. nor can they cannot be managed effectively by individual countries. well-recognised threats in the areas of biological weapons, surveillance for bioterrorism, laboratory security and antimicrobial resistance are discussed. we also highlight emerging new areas of threat in the intersection of health security and cybersecurity and enabling of precision harm through big data in medicine. against this backdrop, we outline below the need for new governance and risk analysis approaches that are global and cross-disciplinary. it has been possible since to create synthetic viruses in a laboratory, when researchers at the state university of new york at stony brook published the synthesis of the poliovirus in science (cello et al. ). there are now over private companies in synthetic biology (global engage ), which are self-regulated with voluntary codes of conduct (samuel et al. ). whilst prior biosecurity efforts focused on the biological materials themselves and the inherent challenges of securing and accounting for these materials within laboratories, genetic code can now be transmitted rapidly and used to create new or modified infectious pathogens (kelle ). in the specific case of synthetic infectious agents, the unique characteristic of transmissibility from person-to-person raises special concerns about health security. a virus manufactured in one location may spread worldwide and has a major population impact, thus requiring a global risk mitigation approach. the global regulation of synthetic biology pertaining to communicable diseases is challenging, with many models proposed . the tapic (transparency, accountability, participation, integrity and policy capacity) framework provides a guide to good governance (trump ) , but there is no enforceable global governance system in place as yet. the many private synthetic biology companies worldwide remain self-regulated, with voluntary guidelines about reporting of suspicious orders. a case in point is smallpox, for which the genome is fully sequenced and publicly available. in a report, the who (world health organization d) concluded that destroying existing stocks of smallpox in the usa and russia would serve no purpose because the virus can be created using synthetic biology. whilst it is theoretically possible for smallpox to be synthesised in a laboratory, experts have believed this to be a complex task. however, in , canadian scientists synthetically created an extinct poxvirus, closely related to smallpox, for $ , in a laboratory using mail-ordered genetic sequences (koblentz ) , illustrating the very real risk of synthetic smallpox emerging as the cause of a pandemic. in addition to synthetic biology, viruses and bacteria can be engineered for enhanced pathogenicity. a revolutionary new precision tool for gene editing, clustered regularly interspaced short palindromic repeats (crispr cas ) associated nuclease cas , raises concerns about dual-use potential (ran et al. ) . whilst crispr cas offers the prospect of cures to major diseases, it also enables the precision design and construction of engineered microorganisms as potential weapons of mass destruction. in , the us director of national intelligence rated crispr cas as a leading weapon of mass destruction threat (mit technology review ). yet global planning for bioterrorism preparedness is still largely framed by cold war concepts and is largely limited to scenarios involving agents such as smallpox and anthrax in a twentieth-century context. however, contemporary biology presents an expanded threat spectrum with an unlimited array of possible engineered agents that transcend the scope of traditional concepts of biosecurity surveillance, preparedness and counter-measures. the convergence of security threats is illustrated by the use enabling technologies such as the dark web for trade in biological weapons and planning of bioterrorist attacks (macintyre ). a natural epidemic is one which arises in nature, without intervention by humans. unnatural epidemics are those which are caused by human intervention and may be deliberate or accidental release of either naturally occurring or altered pathogens. bioterrorism is the deliberate release of such pathogens to cause harm (venkatesh and memish ) . bioterrorism differs from other forms of terrorism in that a bioweapon is microscopic and invisible, and release of a bioweapon is not always recognisable as a deliberate attack (macintyre and engells ). all category a bioterrorism agents except smallpox also occur in nature. for example, anthrax occurs more frequently in nature (such as through humans handling infected animal carcasses) than as a bioterrorism attack (fong and alibek ) . planning for bioterrorism is underpinned by the assumption that attacks will be recognised as unnatural, but no public health systems exist to differentiate the aetiology of epidemics. tools such as the grunow and finke ( ) criteria are not well known in public health and have low sensitivity for detecting unnatural epidemics when tested against historical events (chen et al. ; macintyre and engells ) . public health agencies do not routinely use such tools and default to the assumption that they all epidemics are natural (macintyre ). there has been an unprecedented increase in the frequency of serious global epidemic risks such as ebola, avian influenza, mers coronavirus and zika virus in recent years (sands et al. ). this cannot be explained solely by environmental and ecological factors, which have changed at a slower rate than the increase in emerging infections. in a recent analysis , we documented that the rate of emergence of new strains of influenza virus infecting humans is escalating at an unprecedented rate, thereby increasing the probability of a pandemic. changes in climate, urbanisation and agricultural practices as well as improved global surveillance may have some role in this phenomenon, but have not changed at the same rapid rate as virus evolution. whether some of these new outbreaks involve engineered agents is unknown and has not been publicly analysed. historically, unnatural epidemics have not always been recognised at the time. for example, the rajneesh salmonella attack in oregon in was not only undetected as a bioterrorist attack, but when a local politician suggested bioterrorism, he was ridiculed by public health officials (mac-intyre ; török et al. ) . operation seaspray, which caused a serratia marcescens outbreak in san francisco in , was not recognised at the time as an open-air test by the us military, which was later disclosed in (wheat et al. ) . the accidental anthrax release in sverdlovsk, soviet union, , was investigated by us experts, who initially incorrectly believed the soviet explanation that it was a natural outbreak (the atlantic ). there are many other examples of failure to correctly identify unnatural epidemics (tucker and zilinskas ) . at a time when genetic engineering and synthetic biology contribute to increased risk of biological attacks, there is a need for new tools and risk analysis methods to rapidly identify unnatural epidemics. yet the grunow-finke criteria despite low sensitivity (macintyre and engells ) remain the best available tool. other tools have been developed but are even less known and used than the grunow-finke criteria (chen et al. ). in addition to risk analysis tools, rapid surveillance methods are required to detect unnatural epidemic signals. new methods for data mining of opensource unstructured data such as social media show promise for rapid epidemic intelligence (the conversation ) but have not yet been utilised for biosecurity (yan et al. ). laboratory safety has been highlighted as a key area of concern, with multiple breaches involving security sensitive pathogens in leading laboratories occurring in recent years (science ). research staff have the unique privilege of working with biological select agents and toxins and possibly the broader group of valuable biological materials (world health organization ), yet insider threat and laboratory accidents are known risks. a related issue is practical impacts of the emerging field of biorisk management in which the previously separate disciplines of biosafety and biosecurity are merged into a singular approach of laboratory biorisk management (cook-deegan et al. ; salerno and gaudioso ) so as to achieve the mutual goal of keeping these materials safe and secure within those areas designated for use and storage. several entities are proposing this combined approach to enhance the risk management process and produce safer laboratories and more secure practices for these materials (association of public health laboratories ). a far too common situation at advanced biomedical research laboratories is a problematic relationship between the researchers and security staff. those relationships must change to reflect a new reality-one in which the research scientist and the law enforcement official are considered members of the same team striving for a mutual goal. those working in laboratories should monitor each other to create a rigorous form of professional self-governance (garrett ) . the implementation of that change will be strategic, for it changes the focus from the substances (biological materials), which because these are alive can be freely found outside the laboratory and continue to defy accurate longterm measurement, to a focus on the behaviours of those who work with these substances-biomedical research scientists, public health officials, clinical laboratorians and others (aquino ) . another threat is a new facet to the insider threat-the potential for radicalisation of health care workers and researchers, for violent extremists continue to defy precise categorisation or predictable profiles and to infiltrate research institutions (macintyre and engells ). in the current age, we must move past our previous solutions dominated by guns, gates and guards and move to a new age in which enhanced personnel security practices through innovative uses of psychology and organisational dynamics will enhance individual and small group accountability and produce a safer laboratory and community at large. doit-yourself biology and biohacker labs fall outside of such systems of governance and are presently self-regulated, but the technology is easily accessible for terrorist groups to establish clandestine labs. no systems exist to detect such laboratories. the risk of emerging infections is increasing, whilst our ability to treat infections with antibiotics is decreasing. antibiotics represent one of the major public health achievements of the twentieth century, which together with vaccines are responsible for the dramatic reduction in morbidity and mortality caused by infections. whilst antimicrobial resistance is not new, its cascading global impact and threat to national and global security are considerable. within a decade, antimicrobial resistance, driven by prolific misuse in animals, humans and food production, and limited development of new antimicrobial options, will present a significant threat to humanity in the twenty-first century. a key solution is to judiciously use our remaining antibiotic options, yet even in relatively well-off organisation for economic cooperation and development (oecd) nations, antibiotic misuse continues virtually unabated in both the human and veterinary sectors (world health organization b). the world health organization ( b) and other key stakeholders have indicated the critical need for immediate global antimicrobial optimisation, reduction in unnecessary usage, and the roll-out of stewardship across health and agriculture sectors. for example, there has been a % global increase in use of last resort antimicrobials (carbapenems) over the last years, and both low-income countries and high-income countries are using substantially more antibiotics per capita than in previous decades (review on antimicrobial resistance ). as with other infectious diseases threats, a global response to this threat is urgently required, with human movement across national borders, threatening antimicrobial viability, even in countries with active surveillance and control programmes. the vertical management of antibiotic use in the human and animal sectors as well as in agriculture and food production must also be addressed in an integrated way, as the volume of use is much higher in these other sectors. a key strategy, in terms of policy, will be the adoption of the one health model for amr supported by who ( a), the eu, and the usa (centers for disease control and prevention ). whilst policy and regulation have progressed considerably in health care environments, a parallel set of strategies will need to be implemented in farming, agriculture and veterinary medicine, which account for around % of antibiotic use (food and drug administration ). thus far, strategies utilised across contexts have largely failed to set national targets to reduce antibiotic use in animal agriculture and nor mandate the collection of antibiotic usage data (martin et al. ) . consumer-led strategies-for example, the marketing of antibiotic free products-are one such strategy that may be used to promote sustainable use of antibiotics in the non-health sector (doyle et al. ) . increasing public awareness of the connections between animal and human health-a cornerstone of the one health approach-will be central to this strategy. there is growing recognition of the costs and significance of amr. multi-resistant organisms are emerging at much higher rates than seen previously, with urgent attention needed to mitigate a risk which is predicted in one report to be the greatest global burden of disease (review on antimicrobial resistance ). one recent estimate indicates that by , infections from resistant bacteria may overtake cancer as the leading cause of death in the world and cost us$ trillion. this estimate has been questioned and likely an overestimate, but amr nonetheless causes a significant burden of disease (de kraker et al. ). the world is in urgent need of new strategies in the human, animal, agricultural and food industries. this includes reviewing how we price/value antimicrobials, incentives for new antimicrobial development and judicious use, and restrictions around use across sectors. in addition, serious amr could be engineered and released as an act of bioterrorism, given the availability of technology such as crisp cas (macintyre and bui ). a longer-term model of population risk (versus immediate individual risk of often minor infection) is required to guide everyday use and mitigate this global threat. whether a bioterrorist attack, pandemic or infections complicated by amr, the risk is increasing as outlined above. infectious diseases do not respect international borders and can spread rapidly around the world. the continued growth in large urban areas, and megacities in particular, in which high population densities represent optimum conditions for spread of infection merits significant attention in biosecurity. this risk is heightened for megacities in developing countries in which serious gaps exist in public health surveillance for early detection of epidemic threats, together with inadequate critical infrastructure and other preparedness resources. prevention, mitigation and control of these threats, therefore, require efforts at local, national and global levels. despite the call for a one health approach (rabinowitz et al. ) , there is no suitable system for governing use of antimicrobials across human health, animal health and food production, and often no coordination of efforts across these sectors. in considering new technologies such as crispr cas (bulletin of the atomic scientists ). the cartagena protocol was developed to address regulation of movements of living modified organisms (lmos) resulting from biotechnology from one country to another, but has focused on ecology and biodiversity and has not been utilised for human biosecurity. the tapic framework (trump ) is a good starting point for considering how existing regulations can be improved and enforced and how new ones could be developed globally. the key needs in risk analysis for biosecurity are timely surveillance and identification of biosecurity threats, risk analysis of impacts and differentiation of natural versus unnatural outbreaks. traditional disease surveillance lacks the timeliness required for rapid detection of emerging and re-emerging pathogens. current public health systems rely on validated data from sources health systems, such as hospital and laboratory data, which are important for analysing trends over time, but do not meet rapid epidemic intelligence needs for early detection of epidemics (yan et al. ). epidemics, defined by a reproductive number greater than one (macintyre and bui ), grow exponentially, so every day of delay in detection could substantially increase the morbidity and mortality burden. mathematical models, typically of the form of deterministic systems of nonlinear differential equations, are often used to gain insight into the transmission dynamics and impact of natural and unnatural emerging and re-emerging infectious diseases that threaten health security, such as disease pandemics (nuno et al. ; nuño et al. ; sharomi et al. ) and the deliberate release of agents of bioterrorism, such as anthrax (brookmeyer and blades ; mushayabasa ; pantha et al. ) and smallpox (banks and castillo-chavez ; del valle et al. ; kaplan et al. ; meltzer et al. ). these models, combined with robust health data analytics, computational and data visualisation techniques and numerical simulations provide a realistic, rapid real-time assessment of threats to public health security. furthermore, informing these models with data generated from modern diagnostic tools that are capable of detecting asymptomatic cases with high degree of sensitivity and specificity (such as peptide-based immune-signaturing or low-cost paper-based rna sequencing) (legutki et al. ; navalkar et al. ; pardee et al. ; stafford et al. ) , and using knowledge of prior bioterrorism attacks and natural disease outbreaks allow for a realistic proactive prediction of future threats before they are detected by the public health system. these approaches allow for a more proactive disease surveillance for human diseases as well as veterinary surveillance for zoonotic pathogens that can mutate and cause major burden in human populations. other modelling paradigms, such as agents-based and other datadriven statistical and stochastic modelling approaches (halloran et al. ; hu et al. ; kaplan et al. ; nuño et al. ) , are also being used for this purpose. a stochastic approach to risk analysis allows model inputs to exhibit a degree of uncertainty. in contrast to deterministic models, the inputs follow various forms of probability distributions. risk is computed by sampling these input distributions many times. therefore, the outcome of a stochastic risk model is a distribution of risk-rather than a single value. the key advantage is that in addition to analysing outcomes, it allows for an analysis of the probability of these outcomes. it also allows for easy scenario analysis and sensitivity analysis. these can all assist decision-makers in taking intervention measures and allocating resources. one such example is a stochastic risk model (hill et al. ) of zoonotic and pandemic influenzas, with a focus on human infection with avian influenza. however, there are few real-time models with applicability in operational public health, with most modelling occurring in academia without real-time applicability for disease control . end-users in the public health system do not have much knowledge or nor trust in modelling, and do not use it widely for disease control (muscatello et al. ) . availability of simple, transparent tools that can assist with pressing questions such as surge capacity planning during the influenza season is what stakeholders value (muscatello et al. ) . although mathematical modelling has enjoyed widespread popularity within the academic public health community in terms of using it to predict epidemics as well as to assess and propose effective containment strategies (newall et al. ) , the use of genetic data (despite its huge potential to provide much deeper insight) for predictive purposes has not yet become a mainstream tool in public health practice (dudas et al. ) . virus phylogeography and phylodynamics are methods developed to utilize viral dna sequences to explore the evolution of pathogens by estimating their ancestry. these methods also show promise for public health surveillance, but are not as well developed or used in public health practice. it has only been somewhat recent that more focus has been on combining descriptive phylogenetic approaches with other modelling methods that attempt to predict epidemics. phylogenetic and phylogeographic analyses can be combined with methods for epidemic modelling to analyse risk factors and predictors of risk in a geospatial and genetic context. geographic information systems (gis) provide a further platform for public health researchers to take a map of an area and add layers of information regarding demographics, disease prevalence and socio-economic status (mondini and chiaravalloti-neto ; rushton ) . when overlaying multiple types of information, relationships and correlations can be discovered, adding analytical value beyond traditional descriptive approaches (doku and lim ) . patient data distributions and timestamps are significant factors in determining the specifics of an epidemic disease. hence, gis techniques such as emerging hot spot analysis and grouping analysis (van steenwinkel et al. ) allow for risk analysis of healthrelated concerns as correlated to location. for example, emerging hot spot analysis (wang et al. ) can help monitor changes and trends of an epidemic disease, such as identifying locations representing new or intensifying hot spots. new risk analysis methods are required to flag epidemics for urgent intervention, as illustrated by the catastrophic consequences of inaction with the ebola epidemic in west africa (world health organization ). we have shown that a simple risk prediction tool can be developed which identifies regions at high risk of severe outcomes of epidemics (argisiri et al. ) . such a tool, which considers disease specific, geographic, political, social, situational and contextual factors, could be used to prioritise epidemic response in situations of limited resources and reduce the impact of serious events. finally, the vast quantities of publicly available, unstructured data such as news feeds, social media and other public information offer potential for rapid epidemic intelligence and early detection, but are not yet accepted in public health (yan et al. ) . google, twitter and other sources have shown early promise for rapid disease detection by using algorithms and natural language processing to detect signals for epidemics, but are still eschewed by traditional public health systems (schmidt ) . rapid epidemic intelligence tools based on social media and news feeds could supplement traditional health system based, validated surveillance systems by providing more timely signals for epidemics of concern (yan et al. ) . we have shown that the ebola epidemic of could have been detected months earlier than it was using a novel twitter-based tool (yan et al. ). in addition, risk analysis frameworks play an important role in biosecurity decision-making and policy. using the approach of multiple criteria based upon emerging biotechnologies such as synthetic biology, traditional risk assessment such as health and environmental data, and other characteristics such as the uncertainty, reversibility, manageability of risk and levels of public concern (cummings and kuzma ; trump et al. ) , can be integrated to provide evidence-based information to government, academia and non-governmental organisations. such risk analysis methods could assist decision-makers to rank policy priorities and to improve the governance of biosecurity. whilst new risk analysis methods and tools are continually developed, many of the established methods for risk analysis of emerging infections are used separately and in different contexts. with increasing biothreats in society, these methods could be better integrated to add value improve the capacity to predict and mitigate risk. biosecurity is affected by cybersecurity concerns, but planning for biosecurity often fails to consider critical dependencies with information technology and computing. for example, mitigation and prevention of bioterrorism require surveillance for trade in bioweapons. the dark web offers terrorists a platform for trade in weapons, including bioweapons. numerous dark web marketplaces such as silk road and alphabay have been shut down by us law enforcement in recent years, but new ones continue to emerge (business insider australia ). whilst such market places are better known for trading in drugs and weapons, in a new york university student was arrested for attempting to purchase a category b bioterrorism agent, ricin, on the dark web (new york post ) . this highlights the need for integration of cybertechnology as a tool in prevention and surveillance for bioterrorism. surveillance for planned bioterrorism is not as well advanced in this realm as it is for traditional forms of terrorism. law enforcement agencies employ surveillance of the dark web and social media to detect chatter about planned terrorism, but the focus has been far less on bioterrorism. for example, surveillance for purchase of genetic code to create dangerous viruses failed to pick up the canadian scientists who created an extinct poxvirus in the laboratory using mail-order dna (science ). the world first knew about this experiment only when the scientists announced it. whilst this group was legitimate and not engaged in bioterrorism, the same methods for procurement which they used could well be used by terrorist groups. therefore, surveillance is required to detect such activity and prevent bioterror attacks. it was reported in that the unique health records of all australians are available for sale on the dark web, a fact uncovered by a reporter, not by law enforcement or government, exposing authorities as completely unprepared (bickers et al. ) . cyberattacks and cybertheft affect all facets of society, from banking and health to critical infrastructure (the age ). in many cases, the outcome of a cyberattack is loss of money or assets. however, if critical infrastructure or health systems are attacked, human lives may be lost. for example, if the power grid of a city is compromised, this has many flow-on effects on health systems, such as loss of functioning of critical equipment in intensive care units or operating theatres, or even for home interventions that rely on power such as nebulisers or oxygen (lee et al. ) . hospitals rely on generators as backup, but these can fail in the event of a disaster (parson ; sifferlin ) . the escalation of ransomware attacks on hospitals, which are poorly prepared and easy targets, can bring whole health systems to standstill, as seen within the uk nhs and us hospitals (deane-mckenna ; gillett ; landi ) . the goal of most health systems is to achieve paperless operations, to which the electronic patient medical record is central. yet the zeal for electronic health (e-health) has progressed with very little consideration of cybersecurity, leaving hospitals vulnerable to ransomware attacks (cbsnews ). the aspiration of health systems towards the e-health record is driven by the desire to improve care, protect patient safety and reduce medical errors (australian digital health agency ). the e-health record (ehr) has also been embraced by researchers as a means to efficient health research through data linkage of large administrative databases (powell and buchan ) . for example, data linkage was used to show that ct scans are associated with childhood cancer (mathews et al. ) . whilst big data allows new ways of conducting medical research, the risk of hacking of the ehr has not been adequately mitigated in health care. education and training in hospital and health management does not routinely offer courses in cybersecurity, leaving health planners and hospital managers unaware of the risk and underprepared. participants in the us federal medicare ehr incentive program have to attest that they have a fundamental cyber security programme and have adopted certified ehr technology (the office of the national coordinator for health information technology ). hospitals attesting meaningful use are legally bound to meet specific standards, including protection of the her, and can be audited. however, even this system has not protected us hospitals from cyberattacks (cbsnews ), and many countries do not have any such safeguards. precision medicine has revolutionized medicine, with the ability to tailor treatments for individuals by combining detailed medical, genetic and other patient information. this, however, also leads to the possibility of the same information being used to tailor "precision harm". it is well recognised that individuals can be targeted by biological weapons (macintyre and engells ), but convergence of technology opens new avenues for precision harm of individuals. the catastrophic hacking of the us office of personnel management (opm) in (mukherjee ) exposed data on over million us federal employees. at the same time, anthem health, the largest provider of health insurance to these employees, was also hacked (tuttle ) . data linkage would allow the perpetrators to access the sensitive personal medical information of employees, identify their medical vulnerabilities and plan targeted attacks, such as medication tampering or hacking of digital medical devices. the risks posed by hacking digital medical devices such as pacemakers and insulin pumps are also cause for concern (francies ) . this includes more extreme scenarios in which individuals with high political profiles or other strategic value could be assassinated by manipulation of their medical devices, tampering with their medication regimen or the design of microbial agents matched to their individual genetic profile. former us vice president dick cheney had his pacemaker wireless function disabled to mitigate such risk (peterson ) . if hostile states, organised crime groups or terrorist gain digital medical information on defence or security professionals, government officials or judges, it may become a more attractive option to more obvious methods for causing harm. figure illustrates the potential for precision harm targeting high profile individuals, enabled by convergence of technologies. in the example provided, a federal judge could be targeted in several different ways, including biological weapons, hacking of digital medical devices, medication tampering, interference with scheduled medical procedures or use of toxins or immune modulators, once a roadmap for precision harm is created. this example could apply to linkage of data from the opm and anthem health hacks to create personalised medical profile for federal employees. these examples illustrate the convergence of cybersecurity and health security and the need for more integrated approaches to prevention and mitigation of emerging risks in health care. in summary, we face rapid advances in science and technology, a corresponding escalation of risk to biosecurity, and convergence of multiple security threats which have traditionally been addressed separately. the changing landscape in biothreats and convergence with other areas of security can no longer be addressed in the traditional narrow, healthcentric way. the solution requires a multidisciplinary, global approach to security, whilst meeting local government regulatory requirements. we need new methods to prevent, identify and mitigate threats to biosecurity, which require cooperative thinking across national and professional boundaries. globally, health, law enforcement, defence and intelligence agencies will need to collaborate and pool their information and expertise. new risk analysis methods and surveillance tools need to be developed, and old methods may need to be used in new ways. this must be addressed in a coordinated global way to ensure risk is minimised. radicalized health care workers and the risk of ebola as a bioterror weapon a risk analysis approach to prioritising epidemics-ebola virus disease in west africa as a case study biorisk management for clinical and public health laboratories benefits of having a my health record hackers are offering to sell the medicare details of australians on the dark web statistical models and bioterrorism: application to the us anthrax outbreak an overview of the epidemiology and emergence of influenza a infection in humans over time can the bioweapons convention survive crispr? authorities just took down alphabay, an online black market times bigger than silk road hack on d.c.-area hospital chain reverts them to paper chemical synthesis of poliovirus cdna: generation of infectious virus in the absence of natural template antibiotic/antimicrobial resistance a systematic review of risk analysis tools for differentiating unnatural from natural epidemics about the protocol societal risk evaluation scheme (sres): 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need for a paradigm shift pandemics, public health emergencies and antimicrobial resistance-putting the threat in an epidemiologic and risk analysis context current biological threats to frontline law enforcement: from the insider threat to diy bio law enforcement executive antibiotics overuse in animal agriculture: a call to action for health care providers cancer risk in , people exposed to computed tomography scans in childhood or adolescence: data linkage study of million modeling potential responses to smallpox as a bioterrorist weapon top u.s. intelligence official calls gene editing a wmd threat spatial correlation of incidence of dengue with socioeconomic, demographic and environmental variables in a brazilian city anthem's historic health records breach was likely ordered by a foreign government translation of real-time infectious disease modeling into routine public health practice dynamics of an anthrax model with distributed delay acta applicandae mathematicae: an international survey application of immunosignatures for diagnosis of valley fever ex-nyu student gets years in jail for trying to buy ricin cost-effectiveness analyses of human papillomavirus vaccination assessing the role of basic control measures, antivirals and vaccine in curtailing pandemic influenza: scenarios for the us, uk and the netherlands protecting residential care facilities from pandemic influenza optimal control applied in an anthrax epizootic model rapid, low-cost detection of zika virus using programmable biomolecular components -year flood paralyzes texas medical center yes, terrorists could have hacked dick cheney's heart the plus alliance mobilises to solve problems of global security electronic health records should support clinical research toward proof of concept of a one health approach to disease prediction and control genome engineering using the crispr-cas system review on antimicrobial resistance ( ) tackling drug-resistant infections globally: final report 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coordinator for health information technology ( ) guide to privacy and security of electronic health information a large community outbreak of salmonellosis caused by intentional contamination of restaurant salad bars synthetic biology regulation and governance: lessons from tapic for the united states a decision analytic model to guide early-stage government regulatory action: applications for synthetic biology the smallpox epidemic in aralsk, kazakhstan, and the soviet biological warfare program cyberdisaster: how the government compromised our security assessing biosecurity practices, movements and densities of poultry sites across belgium, resulting in different farm riskgroups for infectious disease introduction and spread bioterrorism-a new challenge for public health measuring the deconcentration of housing choice voucher program recipients in eight us metropolitan areas using hot spot analysis infection due to chromobacteria; report of cases who, geneva world health organization ( ) report of the ebola interim assessment panel antimicrobial resistance world health organization ( b) global action plan on antimicrobial resistance world health organization ( c) international health regulations (ihr) world health organization ( d) who advisory committee on variola virus research: report of the eighteenth meeting utility and potential of rapid epidemic intelligence from internet-based sources the authors are affiliated with global security key: cord- -vv qsq authors: stuart, r. m.; abeysuriya, r. g.; kerr, c. c.; mistry, d.; klein, d. j.; gray, r.; hellard, m.; scott, n. title: the role of masks in reducing the risk of new waves of covid- in low transmission settings: a modeling study date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: vv qsq objectives: to evaluate the risk of a new wave of coronavirus disease (covid- ) in a setting with ongoing low transmission, high mobility, and an effective test-and-trace system, under different assumptions about mask uptake. design: we used a stochastic agent-based microsimulation model to create multiple simulations of possible epidemic trajectories that could eventuate over a five-week period following prolonged low levels of community transmission. setting: we calibrated the model to the epidemiological and policy environment in new south wales, australia, at the end of august . participants: none intervention: from september , , we ran the stochastic model with the same initial conditions (i.e., those prevailing at august , ), and analyzed the outputs of the model to determine the probability of exceeding a given number of new diagnoses and active cases within five weeks, under three assumptions about future mask usage: a baseline scenario of % uptake, a scenario assuming no mask usage, and a scenario assuming mandatory mask usage with near-universal uptake ( %). main outcome measure: probability of exceeding a given number of new diagnoses and active cases within five weeks. results: the policy environment at the end of august is sufficient to slow the rate of epidemic growth, but may not stop the epidemic from growing: we estimate a % chance that nsw will be diagnosing at least new cases per day within five weeks from the date of this analysis. mandatory mask usage would reduce this to - %. conclusions: mandating the use of masks in community settings would significantly reduce the risk of epidemic resurgence. there is increasing evidence that localized suppression or even elimination of covid- is possible with interventions such as physical distancing, lockdowns, travel restrictions, testing, tracing, and quarantine. this outcome was very likely achieved in several countries, including new zealand, iceland, taiwan, thailand, and vietnam, among others [ ] . however, even if the epidemic has been locally controlled, new outbreaks can emerge if community transmission has not been eliminated and cases escape detection or quarantine, or if infected people arrive from abroad or interstate and interact with the local community (as recently seen in cities such as melbourne and auckland). in settings with low numbers of active covid- infections, minimizing the risk of epidemic resurgence is essential for sustainability. therefore, it is crucial to identify and quantify strategies to reduce this risk. in this paper we focus on new south wales, australia's most populous state with . million residents, as an example of a setting with low transmission, high mobility, and a well-functioning test-and-trace system. after an initial wave of covid- infections in march and subsequent lockdown in april, new south wales began relaxing physical lockdown measures over may and was experiencing near-zero case counts by the start of june, with students back at school, businesses reopening and social/community activities resuming. in late june several clusters of new infections were detected, which subsequently led to a two-month long period of low but steady case counts (between - newly detected cases per day). this experience contrasts sharply with that of the neighboring state of victoria, which had also achieved near-zero case counts by early june but which then experienced a large second wave, with , new cases detected between june and august, % of which have been traced back to just four index cases [ ] . the dynamics of covid- transmission are complex, and in low-transmission settings the probability of maintaining epidemic control depends on numerous factors outside of policy control, including the characteristics of people who get infected: the size of their households, the type of work that they do, and a number of other socio-economic factors that may influence their contact networks, access to testing and capacity to self-isolate. several studies have pointed to the role of superspreading events and overdispersion of infections in covid- transmission [ ] [ ] , including work by our group examining the seattle epidemic found that infections are overdispersed, with ~ % of infected people not transmitting at all, while % cause half of all onward transmission [ ] , study on the role of superspreading events. as a result, even with physical distancing, high levels of testing, and rapid contact tracing, there is still a non-zero probability that a sustained outbreak could occur depending on who gets infected and where. there are numerous non-pharmaceutical interventions (npis) that jurisdictions can adopt to improve their resilience to renewed epidemic waves whilst still allowing social and economic activity to continue. such npis include physical distancing regulations, hygiene protocols, and the use of face masks, all of which have been recommended by the world health organization (who) [ ] . these npis are supported by a growing body of evidence regarding their efficacy in preventing individuallevel covid- transmission [ ] [ ] [ ] [ ] [ ] . however, australia's response through to the end of august focused on the first two measures, with only victoria having mandated the use of face masks -and even then only after the second wave of infections was well underway and lockdown measures were in place -while other jurisdictions have only encouraged mask use in particular settings. is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted september , . . in this work, we assess the likelihood of epidemic rebound following a prolonged period of low, stable transmission and relatively high community mobility, using a stochastic agent-based mathematical model of covid- . because the model is stochastic, we can run it multiple times and evaluate the probability of observing a given outcome among all possible outcomes. we use this feature to evaluate the probability that new south wales will experience an epidemic resurgence under different assumptions about the adoption of masks/face coverings. we began by simulating a population representative of new south wales by taking data on the age and sex composition of the population from the census (the latest available), and using it to create a model population of agents with similar characteristics. the simulations consist of , individual agents, who are dynamically scaled based on prevalence to represent the total new south wales population of . million. the dynamical scaling means that whenever the proportion of susceptible agents falls below a threshold of %, the number of agents in the model is increased; further implementation details can be found in section . . of kerr et al [ ] . next, we created contact networks for these agents. the governmental response to covid- in new south wales consisted of a set of highly context-specific policies covering individuals, businesses, schools, and other types of organizations. to model these policies, we allow agents in the model to interact over five types of contact network: households, schools, workplaces, and static and dynamic community networks. the static community network consists of interactions with friends, colleagues, or other known associates who come together on a regular and predictable basis, and contains four sub-networks: professional sports, community sports/fitness/leisure clubs, places of worship, and socializing with friends. the dynamic community network consists of interactions in which people interact with strangers or random groups of people, and contains seven separate subnetworks, representing: ( ) arts venues such as museums, galleries, theatres, and cinemas, ( ) large events such as concerts, festivals, sports games, ( ) pubs and bars, ( ) cafes and restaurants, ( ) public parks and other outdoor settings, ( ) public transport, ( ) all other community settings. the method for constructing these networks is described in our previous study of the victorian epidemic [ ] and is based on the methodology of the synthpops python package [ ] . we used an agent-based microsimulation model, covasim [ ] , developed by the institute for disease modeling and previously adapted by our group to model the victorian epidemic [ ] . covasim contains detailed descriptions of age-dependent disease acquisition and progression probabilities, duration of disease by acuity, and the effects of interventions including symptomatic and asymptomatic testing, isolation, contact tracing, and quarantine, as well as other npis such as physical distancing, hygiene measures, and protective equipment such as masks. importantly, it also captures individual variability, with viral loads varying both between individuals and over time. throughout march, the policy response to covid- in new south wales progressed from guidelines encouraging precautionary handwashing and distancing to a much more restrictive "lockdown" phase, in which people were only allowed to leave their houses for a limited number of reasons. this phase was maintained throughout april and then gradually eased over may-july. is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted september , . . figure presents a summary of how contact networks and the relative risk of covid- transmission in different settings changed as policies evolved. some of these changes in transmission risk are derived from available data [ ] , while others are taken from a similar modeling exercise conducted in victoria, in which a panel of australia-based experts reviewed the likely effect of policies on transmission risks [ ] . further details of all policies and how we model their effects on transmission risk are contained in supplementary table . most relevantly for our subsequent analyses, we assume that the proportion of new south wales residents who wore masks in dynamic community settings increased over august to reach % by the end of the month. figure . relative changes in network structure and transmission risk across different settings in new south wales over march-august. the absolute transmission risk varies by setting and is highest in household and lowest in outdoor settings (see [ ] for details). we initialized the model on march , by seeding infections in the model population, with the number of seed infections chosen as part of the calibration process. the model was calibrated to data on ( ) the number of tests conducted and ( ) the daily number of cases diagnosed in nsw, excluding cases acquired overseas, by performing an automated search for the values of the percontact transmission risk and the number of seed infections that minimized the absolute differences between the model projections and the data. we repeated the initialization times, each time with a different set of people infected at the beginning of the simulation. figure displays the outcome of this, with the model capturing the initial outbreak, the decline in cases following the april lockdown, and then the gradual increase in june/july as policies eased, new cases arrived from interstate, and new clusters began to form. by the end of august, we estimate just over active infections in new south wales. is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted september , . . we use the model to investigate the probability of a setting with low transmission and high mobility experiencing a resurgence in cases, grounding the analysis based on the policy settings and epidemic state of new south wales at the end of august. to calculate this probability, we reinitialize the model on august , and project forward by five weeks using the parameter values obtained via the calibration process, and beginning with the estimated epidemic state on august , . we repeat this times, with each iteration representing a different realization of the possible future transmission dynamics. we then calculate the proportion of simulations in which the number of cases being diagnosed per day exceeds different thresholds within five weeks. as a baseline, we assume that the policy and behavioral settings in place at the end of august continue, including the assumption that % of adults wear masks while at work and when participating in community-based activities along with strangers or random groups of people. we then model two alternative scenarios: . no mask scenario: assuming negligible mask use; . near-universal mask uptake: assuming that % of the adult population wear masks while at work and when participating in community-based activities along with strangers or random groups of people. the individual-level effectiveness of masks at reducing covid- transmission is difficult to determine, and will be influenced by the level of restrictions or npis already in place. a comprehensive meta-analysis covering studies of mask effectiveness concluded that masks are associated with a reduction in infection for mask-wearers by at least one-third compared to control groups [ ] . we assume that masks will reduce the per-contact probability of transmission by an additional % relative to a baseline in which other npis are in place. we also conduct a sensitivity analysis in which the individual-level effectiveness of masks is assumed to be %. beginning from a point with ongoing low levels of community transmission, high mobility, and with % of adults wearing masks at work and in settings with unknown groups of people, we estimate that there is a % chance that transmission will increase to at least new cases per day within five weeks ( figure ). if masks were not worn, the probability would increase to %, indicating that the . cc-by-nc-nd . international license it is made available under a perpetuity. is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted september , . . https://doi.org/ . / . . . doi: medrxiv preprint current level of mask usage does not have a great impact on containing the probability of a resurgent epidemic. however, we find that under the near-universal mask uptake scenario, the probability of diagnosing more than cases per day within five weeks would fall to % ( figure a) . furthermore, we estimate that the total number of infections over the next five weeks would be % lower than under a scenario in which masks are not used, largely driven by a % reduction in infections transmitted in dynamic community settings ( figure c ). under all scenarios, we estimate that the median number of daily infections is likely to continue to gradually increase ( figure d) . we also conducted a sensitivity analysis in which individual-level mask effectiveness was assumed to be %. under this scenario, we estimate an % probability of diagnosing more than new cases per day within five weeks if mask uptake does not change, or % under the high mask scenario. overall infections over the next five weeks would be % lower if masks were adopted with high uptake ( figure s ). evidence from numerous other settings has shown that as long as the population remains susceptible to covid- infection, reopening society is likely to lead to new epidemic waves unless a welloperating test-and-trace strategy is in place [ ] , [ ] - [ ] . in this work, we examined a lowtransmission, high mobility setting with limited mask usage, and found that high levels of testing and contact tracing have thus far succeeded in controlling the epidemic, but do not eliminate the risk of an epidemic resurgence. at the time of writing, case numbers in new south wales had is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted september , . . decreased from ~ /day over july to < /day by the end of august, which may indicate that test-andtrace efforts in this instance were sufficient to curtail the risk of epidemic resurgence. however, our main finding does not depend on the exact date of the analysis; as long as viral transmission remains in the community, the probability of epidemic resurgence (e.g., an untraceable cluster, a failure of quarantine, or a superspreading event) remains. we found that the use of masks would reduce the probability of epidemic resurgence in new south wales: if the use of masks was mandated in new south wales, we estimate that the probability of diagnosing at least new cases per day within five weeks would reduce from % to %. given that masks are an intervention with low social and economic costs, and containing an epidemic resurgence is extremely disruptive and costly (with treasury estimates suggesting that victoria's stage restrictions will result in an au$ - billion reduction to national gdp in the september quarter [ ] ), this reduction in risk is of major significance and suggests that a policy of mandatory mask use is likely to have an extremely high benefit-to-cost ratio. this study adds to a sizable body of evidence supporting the adoption of face masks as a low-cost means of protecting individuals from acquiring covid- [ ] , [ ] , [ ] , [ ] . modeling studies have shown that the population-level effects of masks depend on the state of the epidemic. a study from israel showed that masks are particularly effective when the effective r is close to , and can determine whether a low-level epidemic tips into an outbreak or not [ ] . in higher transmission settings where the effective r is greater than , two studies found that masks are most effective when used in conjunction with a collection of other npis [ ] , [ ] . to our knowledge, no studies to date have examined the extent to which face masks can prevent a resurgent outbreak in low-transmission settings. furthermore, by using a model that already incorporated the numerous other covid- control measures in place in new south wales, we illustrate that face masks have benefit even in the context of a well-functioning test-and-trace system. there are several limitations to this study. firstly, the mathematical model that we use is subject to the usual limitations of mathematical models, including uncertainty around the parameters that characterize covid- transmission and disease progression, uncertainty around the impact of interventions and behavioral changes, and reliance on data sources (such as the number of covid- cases by likely source) that may be incomplete and/or subject to revision. to the extent possible, we managed these issues by sampling parameters from probability distributions and conducting sensitivity analyses around the efficacy of masks. secondly, we made assumptions about the proportion of contacts of diagnosed cases that can be traced within a certain number of days; further data on these proportions would greatly improve model estimates. thirdly, our analyses assume that the policy environment in new south wales would be relatively slow to react to an increase in case numbers; we focused on the question of quantifying the likelihood of diagnosing more than cases/day on the assumption that this would equate to a high likelihood that new south wales would enter a more restrictive phase of lockdown, but a faster policy reaction, as recently seen in auckland, would change the nature of the results seen here. our work suggests that adoption of face masks by the general public could substantially reduce the risk of new epidemic waves. given that individuals are already requested to isolate if they have been diagnosed with covid- or are displaying symptoms, a major benefit of masks is in controlling asymptomatic transmission, which is estimated to make up approximately one third of all transmissions. the use of masks also has a role in reinforcing the importance of other npis. not only does this have positive health outcomes in terms of reducing the number of covid- infections is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted september , . . and associated mortality, but it also has clear social and economic benefits by mitigating the need for more extreme lockdown measures that are required to curtail epidemic resurgences once they have begun. table s . effects of policies on transmission risk in new south wales description of policy changes and their effects schools school attendance rates in nsw had already dropped by % by march [ ] , and on march the nsw premier advised that although schools remained open, parents were encouraged to keep their children at home for online learning [ ] . school attendance rates subsequently dropped to % of their pre-covid levels [ ] . however, attendance quickly returned to pre-covid levels shortly after schools reopened in mid-may [ ] . to model this, we removed % of contacts between school children and then restored them again as schools opened, but with the relative transmission risk set to % of its pre-march levels to account for additional safety measures in place for school activities [ ] (figure ). according to survey data from the australian bureau of statistics, almost half of working australians were working from home in late april/early may [ ] , which is roughly consistent with google movement data indicating that % fewer people were at work over that period compared to baseline. workplace-based activities increased as covid restrictions eased, but remained % lower over june-july compared to baseline. in the model, we removed % of workplace contacts and then restored them so that the workplace network was back to % of its pre-covid size by the beginning of july ( figure ). as with schools, we set the relative transmission risk set to % of its pre-march levels to account for the presence of npis. we assume that almost no contacts occurred over these networks from march to may with the exception of the limited contacts arising from permitted single-person visits., these networks were gradually restored over the period from may to july as restrictions eased ( figure ). dynamic community networks over may-july (negligible mask usage) within new south wales, arts venues such as museums, galleries, theatres, and cinemas, large events such as concerts, festivals, sports games, and pubs/bars were all closed over the period from march to may , after which the networks were gradually restored (figure ). cafes and restaurants, public parks and other outdoor settings, public transport, and all other community settings including essential retail remained open in some capacity throughout the year but with decreased demand and operational restrictions to reduce the likelihood of transmission (e.g., takeaway service only, closure of playgrounds, capacity limits on transport, and physical distancing/hygiene). from august , , the use of masks was mandated in victoria, which led to a marked increase in mask usage across the country. only % of australians wore a mask at least once over the month of june, but % . cc-by-nc-nd . international license it is made available under a perpetuity. is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted september , . reported wearing one at least once over august - , ( % of victorian residents compared to % of residents of other states) [ ] . within new south wales, media sources reported that % of people were wearing face masks on public transport in central sydney in mid-august [ ] . to reflect the gradual increase in mask uptake in the model, we adjust the relative transmission risk assuming that the proportion of adults who wore masks while at work and in dynamic community settings increased over august to reach % by the end of the month. test, trace, and isolate strategies testing, tracing, and isolation strategies have formed a crucial part of the nsw response to covid- , with health authorities encouraging anyone with symptoms (however mild) to get tested. levels of testing increased steadily from ~ , tests/day in april to ~ , +/day by july. in keeping with the increased testing levels, we assume that the daily testing probability for those with symptoms increased from % in april to % by the beginning of june. assuming a symptomatic period of roughly days, this implies that the proportion of symptomatic people who get tested increased from % to %. weekly surveillance reports published by nsw health detail comprehensive contact tracing efforts for all newly identified cases [ ] . reflecting this, we assume that household contacts of confirmed cases can be traced within day of diagnosis, as well as % of school-based contacts, % of work-based contacts, and % of contacts from static community networks (e.g., people met in social gatherings) within days. tracing of dynamic community contacts encountered in locations that require customer registration is also included: we assume that % of contacts from restaurants, cafes, bars, pubs, sports/leisure/fitness centres, arts venues, places of worship, and large events can be traced with a week delay, but only % of contacts from other community settings, including public transport, parks, and retail. in addition to symptom-based testing, we also assume that ~ % of people who are not symptomatic but have been told to quarantine as a result of having been in contact with a confirmed case will get tested. is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted september , . . https://doi.org/ . / . . . doi: medrxiv preprint figure s . the likelihood of epidemic resurgence in new south wales, assuming individual-level mask effectiveness of % countries beating covid- family of four staying at rydges seeded % of second-wave covid cases estimating the overdispersion in covid- transmission using outbreak sizes outside china stochasticity and heterogeneity in the transmission dynamics of sars-cov- controlling covid- via test-trace-quarantine advice on the use of masks in the context of covid- physical distancing, face masks, and eye protection to prevent person-toperson transmission of sars-cov- and covid- : a systematic review and meta-analysis respiratory virus shedding in exhaled breath and efficacy of face masks to mask or not to mask: modeling the potential for face mask use by the general public to curtail the covid- pandemic low-cost measurement of facemask efficacy for filtering expelled droplets during speech estimating the effects of non-pharmaceutical interventions on covid- in europe covasim: an agent-based model of covid- dynamics and interventions modelling the impact of reducing control measures on the covid- pandemic in a low transmission setting institute for disease modeling recovering from coronavirus: data shows how australia is rebuilding as covid- restrictions ease covid- : what's new for effectiveness of isolation, testing, contact tracing and physical distancing on reducing transmission of sars-cov- in different settings feasibility of controlling covid- outbreaks by isolation of cases and contacts impact of delays on effectiveness of contact tracing strategies for covid- : a modelling study pm suggests $ billion cost of stage restrictions in melbourne efficacy of face mask in preventing respiratory virus transmission: a systematic review and meta-analysis impact of population mask wearing on covid- post lockdown estimation of effects of contact tracing and mask adoption on covid- transmission in san francisco: a modeling study coronavirus: nsw school attendance falls per cent as soap, toilet paper shortage hit covid- in schools -the experience in nsw students are being sent back to school in nsw soon -here's what you need to know there were bubbles and balloons': high attendance on first day back at school a guide to nsw school students for term media release -loneliness most common stressor during covid- (media release) media release -covid- anxiety in victoria felt australia-wide (media release) cctv monitors how many are wearing masks on trains covid- weekly surveillance reports -covid- (coronavirus) key: cord- - qpcot p authors: gumel, a. b.; iboi, e. a.; ngonghala, c. n. title: will an imperfect vaccine curtail the covid- pandemic in the u.s.? date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: qpcot p the novel coronavirus (covid- ) that emerged from wuhan city of china in late december continue to pose devastating public health and economic challenges across the world. although the community-wide implementation of basic non-pharmaceutical intervention measures, such as social-distancing, quarantine of suspected covid- cases, isolation of confirmed cases, use of face masks in public, and contact-tracing, have been quite effective in curtailing and mitigating the burden of the pandemic, it is universally believed that the use of an anti-covid- vaccine is necessary to build the community herd immunity needed to effectively control and eliminate the pandemic. this study is based on the design and use of a mathematical model for assessing the population-level impact of a hypothetical imperfect anti-covid- vaccine on the control of covid- . an analytical expression for the minimum number of unvaccinated susceptible individuals needed to be vaccinated to achieve vaccine-induced community herd immunity is derived. the epidemiological consequence of the herd immunity threshold is that the disease can be effectively controlled or eliminated if the minimum herd immunity threshold is achieved in the community. simulations of the model, using baseline parameter values obtained from fitting the model with mortality data relevant to covid- dynamics in the us states of new york and florida, as well as for the entire us, show that, for an anti-covid- vaccine with an assumed protective efficacy of %, the minimum herd immunity threshold for the entire us, state of new york and state of florida are, respectively, %, % and %. furthermore, it was shown that, while a significantly large increase in vaccination rate (from baseline) is necessarily needed to eliminate covid- from the entire us, the pandemic can be eliminated from the states of new york and florida if the vaccination rate is marginally increased (by as low as %) from its baseline value. the prospect of covid- elimination in the us or in the two states of new york and florida is greatly enhanced if the vaccination program is combined with a public mask use program or an effective social-distancing measure. such combination of strategies significantly reduces the vaccine-induced herd immunity threshold. finally, it is shown that the vaccination program is more likely to lead to covid- elimination in the state of florida, followed by the state of new york and then the entire us. in december , the wuhan municipal health commission, china, reported a cluster of a pneumonia-like illness, caused by a coronavirus (sars-cov) in wuhan, hubei province of china [ ] [ ] [ ] . the disease rapidly spread to many countries, resulting in the world health organization declaring the novel coronavirus (covid- ) as a pandemic on march , [ , , ] . as of may , , covid- has caused over million confirmed cases vaccine on the transmission dynamics of the covid- pandemic. the model will be parametrized using available covid- mortality data for the us, the state of new york, and the state of florida to estimate important parameters related to vaccination and other control intervention (notably the parameter related to the reduction in community contacts). we develop a basic model for assessing the population-level impact of a potential hypothetical anti-covid- vaccine. the model is developed by splitting the total human population at time t, denoted by n (t), into the mutually-exclusive compartments of unvaccinated susceptible (s u (t)), vaccinated susceptible (s v (t)), exposed (e(t)), symptomatically-infectious (i s (t), asymptomatically-infectious (i a (t)), hospitalized (i h (t)) and recovered (r(t)) individuals. thus, it should be emphasized that the epidemiological compartment i a also contain individuals who may show mild symptoms of the disease. furthermore, the compartment i h for hospitalization also includes those with clinical symptoms of covid- who are self-isolating at home. the model is given by the following deterministic system of nonlinear differential equations (where a dot represents differentiation with respect to time t): a flow diagram of the model is depicted in figure . the state variables and parameters of the model are described in tables and , respectively. in the model ( . ), the parameter β s (β a ) represents the effective contact rate (i.e., contacts capable of leading to covid- transmission) for symptomatically-infectious (asymptomaticallyinfectious) individuals, < c m ≤ is the proportion of members of the public who wear face-masks (correctly and consistently) in public and < m ≤ is the efficacy of the face-masks. this formulation (i.e., β s = β a ) allows us to account for the possible heterogeneity in the contact rates of infectious with (i s ) or without (i a ) clinical symptoms of covid- . unvaccinated susceptible individuals are vaccinated at a per capita rate ξ v . it is assumed that the hypothetical anti-covid- vaccine is imperfect (i.e., it allows for breakthrough infected in vaccinated susceptible individuals who became infected with covid- ) , with a protective efficacy < ε v ≤ against covid- . the parameter σ represents the progression rate of exposed individuals (i.e., /σ is the intrinsic incubation period of . a proportion, < r ≤ , of exposed individuals show no clinical symptoms of covid- (and move to the class i a ) at the end of the incubation period. the remaining proportion, − r, show clinical symptoms and move to the i s class. the parameter γ s (γ a )(γ h ) represents the recovery rate for individuals in the i s (i a )(i h ) class. similarly, φ s is the hospitalization (or self-isolation) rate of individuals with clinical symptoms of covid- . finally, the parameter δ s (δ h ) represents the covid-induced mortality rate for individuals in the i s (i h ) class. it should be mentioned that, since not much data is available on the expected properties of a future anti-covid- vaccine, we do not assume that the vaccine offers any therapeutic benefits. further, we do not assume that the vaccine wanes during the one-year time period we would choose for the numerical simulations of our model. the model ( . ) is an extension of numerous deterministic models for the transmission dynamics of covid- pandemic, such as those in [ , ] , by explicitly incorporating an imperfect anti-covid- vaccine. to the best of our knowledge, this is the first deterministic model for covid- transmission that explicitly incorporates an imperfect vaccine. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . vaccine efficacy against acquisition of infection σ rate of progression from exposed class to infectious class ( /σ is the incubation period) − r fraction of exposed individuals who show clinical symptoms at the end of the incubation period γ s (γ a )(γ h ) recovery rate for individuals in the i s (i a )(i h ) class δ s (δ h ) disease-induced mortality rate for infectious (hospitalized) individuals φ s hospitalization rate for infectious individuals results the model ( . ) has a continuum of disease-free equilibria (dfe), given by where s u ( ) and s v ( ) are the initial total sizes of the populations unvaccinated and vaccinated susceptible individuals, respectively (so that, n ( ) = s u ( ) + s v ( )). the next generation operator method [ , ] can be used to analyse the asymptotic stability property of the dfe. in particular, using the notation in [ ] , it follows that the associated next generation matrices, f and v , for the new infection terms and the transition terms, are given, respectively, by and, for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint it is convenient to define the quantity r c by: where ρ is the spectral radius, the quantity r c is the control reproduction number of the model ( . ). it measures the average number of new covid- cases generated by a typical infectious individual introduced into a population where a certain fraction is protected, e.g., vaccinated (with the hypothetical vaccine) against covid- . it is the sum of the constituent reproduction numbers associated with the number of new cases generated by symptomatically-infectious humans (r is ) and asymptomatically-infectious (r ia ) individuals. the reproduction number r c will now be interpreted epidemiologically below. as stated above, the reproduction number r c is the sum of the two constituent reproduction numbers, r is and r ia . the constituent reproduction number r is is given by the product of the infection rate of unvaccinated and vaccinated susceptible individuals by symptomatically-infectious humans, near the dfe , the proportion of exposed individuals that survived the incubation period and moved to the symptomaticallyinfectious class ( −r)σ σ = − r and the average duration in the asymptomatically-infectious class , the proportion that survived the exposed class and moved to the asymptomatically-infectious class rσ σ = r and the average duration in the i a class γa . the sum of r is and r ia gives r v . the result below follows from theorem of [ ] . the epidemiological implication of theorem . is that a small influx of covid- cases will not generate a covid- outbreak if the control reproduction number (r c ) is less than unity. the basic reproduction number of the model ( . ) (denoted by r ), obtained by setting the control-related parameters and state variables (i.e., c m , ε m , ε v and s * v ) to zero in ( . ), is given by the quantity r represents the average number of secondary infections generated by a typical infected individual introduced into a completely susceptible population during the duration of the infectiousness of the individual. some of the parameters for model ( . ) were extracted (or estimated based on covid- information) from the literature (table (a)), while the rest (see table (b)) were estimated using mortality data for the entire us, the state of new york, and florida [ ] [ ] [ ] [ ] . a nonlinear least squares method was used to determine the set of parameters that minimizes the sum of the squares of the differences between the cumulative death predictions of the model and cumulative covid-induced mortality) with increasing effectiveness of social-distancing, as expected. for instance, while figure shows that up to , cumulative mortality can be recorded in the us if social-distancing measures were not implemented, the cumulative mortality dramatically decreases to about , (representing about % reduction in cumulative mortality) if strict social-distancing measures were implemented (figure (b)). similarly, % and % reductions in cumulative mortality are, respectively, obtained for the states of new york (figures (c) and (d)) and florida (figures (e) and (f)). these results are consistent with those reported by ngonghala et al. [ ] , which was based on using a novel mathematical model that incorporates the main nonpharmaceutical interventions against covid- (i.e., the model in [ ] does not incorporate an anti-covid- vaccine). this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. for vaccine-preventable diseases, not all susceptible individuals can be immunized for various reasons, such as they are too young to be vaccinated (vaccinating infants or young children can, sometimes, harm the infants/children), they have co-morbidities and weakened immune system (and vaccinating may make their prognosis worse), they are of advanced age or they opt out for cultural, traditional or religious reasons. the question then is what is the minimum proportion of those we can vaccinate that we need to vaccinate so that those that we cannot vaccinate can be protected from developing severe disease or dying of the disease. the notion of herd immunity in the transmission dynamics is associated with the indirect protection, against acquisition of a communicable disease, members of the community receive when a large percentage of the population has become immune to the infectious disease due to natural recovery from prior infection or vaccination [ , ] . the consequence of herd immunity is that individuals who are not immune (e.g., those who cannot be vaccinated or those who have not been infected yet) receive some protection against the acquisition of the disease. the safest and fastest way to achieve herd immunity is obviously vaccination. it should, however, be mentioned that sweden employed the other mechanism for achieving herd immunity in the context of covid- dynamics in sweden [ ] . in other words, the swedish public health agencies aimed to build herd immunity by not implementing the basic community transmission reduction strategies (e.g., social-distancing, community lockdowns, use of face masks in public, contact tracing etc.) implemented in almost every country or community that is hard-hit with the covid- pandemic, opting, instead, to allow individuals to acquire infection and, hopefully, recover from it. although some level of this natural herd immunity has been achieved in sweden, the covid-induced mortality recorded in sweden far exceed those recorded for neighbouring scandinavian countries that implemented the aforementioned non-pharmaceutical interventions [ ] . in this section, a theoretical condition for achieving community-wide vaccine-induced herd immunity is derived. let f v be the fraction of unvaccinated susceptible individuals that have been vaccinated at the disease-free steady-state. that is, further, let it follows from ( . ), ( . ) and ( . ) that the control reproduction number (r c ) can then be re-written, in terms of f v and g v , as follows: which can be simplified as setting r c = in ( . ), and solving for f v , gives the following vaccine-induced herd immunity threshold for the model ( . ): it follows from ( . ) and ( . ) that r c < (>) whenever f v > (<)f c v . hence, we achieved the following results: theorem . . consider the model ( . ). the use of an imperfect anti-covid- vaccine will have the following the result of theorem . is numerically-illustrated in figure , showing an increase in the cumulative covidinduced mortality when f v < f c v and a decrease when f v > f c v . in order to compute the community herd immunity thresholds for the us, new york state and florida state, we compute the respective values of r , using ( . ) with the baseline values of the community contact rates parameters, β a and β s , reduced by % (to account for the effect of the implementation of effective social-distancing measures [ ] ). that is, we set β a = . , β s = . for us, β a = . , β s = . for new york state and β a = . , β s = . for the state of florida in equation ( . ) to obtain the values of the basic reproduction number (r ) for the us, new york state and the state of florida. this gives r = . , . and . , respectively. substituting these values of r (for each of the three populations) in equation ( . ), and noting that the vaccine efficacy is assumed to be % (i.e., ε v = . ), shows that the respective vaccine-derived community herd immunity thresholds for the entire us, the state of new york and the state of florida are %, % and %, respectively (as tabulated in table ). the epidemiological implication of these analyses is that the pandemic can be effectively controlled and/or eliminated in the us and the states of new york and florida if at least %, % and % of the respective unvaccinated susceptible populations are vaccinated (using the hypothetical imperfect vaccine with the assumed protective efficacy of %). it should be mentioned that these vaccine-derived community herd immunity percentages significantly decrease if the vaccination program is complemented with a public face mask use strategy. in particular, table shows that the herd immunity threshold for the us reduced to about % if half the us population wears mask in public . face mask usage with compliance of % to % decreases the herd immunity thresholds for the states of new york and florida to between % to %. these are reasonably attainable in the two states. thus, these simulations show that combining a vaccination program (using the hypothetical anti-covid- vaccine with assumed efficacy of %) with a public mask use strategy significantly enhances the prospect of covid- elimination in the states of new york and florida, and the in entire us nation (albeit elimination is easier to achieve in either of the two states than in the entire us nation). table with β a = . , β s = . for us, β a = . , β s = . for new york and β a = . , β s = . for florida (corresponding to an assumed % reduction in the baseline value of β a and β s , to account for the effect of the implementation of social-distancing measures). the model ( . ) is now simulated to assess the population-level impact of the hypothetical imperfect anti-covid- vaccine in the entire us and the us states of new york and florida. the population-level impact of the vaccination rate (ξ v ) on the burden of the pandemic is monitored first of all. in these simulations, the public face mask use strategy is not implemented. the model ( . ) is then simulated using the baseline parameter values in table (with c m = ε m = ) and various values of ξ v . the results obtained, depicted in figure , show that, for the worst-case scenario without vaccination and public mask usage (i.e., the model ( . ) with ξ v = s v = ε m = c m = ), the us could record up to , daily deaths at the pandemic peak ( figure (a) ), while the states of new york ( figure (c)) and florida ( figure (e)) could record up to , and , daily deaths at the pandemic peaks, respectively. the corresponding projected cumulative mortality for the entire us, the state of new york and the state of florida, for the period february , to september , , are, , , , and , , respectively. these simulations show a dramatic reduction in the daily and the cumulative covid-induced mortality (in comparison to the worst-case scenario without vaccination and mask usage) with increasing values of the vaccination rate ξ v (from its baseline value). in particular, a -fold increase in the baseline value of ξ v for the for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . other parameter values used are as given in table . us resulted in a decrease in the daily number of deaths at the pandemic peak from , to , , representing a % reduction ( figure (a) ). furthermore, this corresponds to a decrease in the projected cumulative mortality from , to , . similarly, a -fold increase in the baseline value of ξ v resulted in a marked reduction of the daily deaths at the pandemic peak to (corresponding to a decrease in the projected cumulative mortality from , to , ). it is evident from figure that a -fold increase in the baseline value of the vaccination rate (ξ v ) for the states of new york (figures (c) and (d)) and florida (figures (e) and (f)) will bring the respective daily deaths at the peak and the projected cumulative mortality to very low levels (i.e., low levels that essentially imply the effective control or elimination of the pandemic). thus, these simulations suggest that, while a significantly large increase in vaccination rate (from baseline) is necessarily needed to eliminate covid- from the entire us, only a small increase (as low as %) in the baseline vaccination rate will be needed to eliminate covid- in the states of new york and florida. these simulations further show that the prospect of disease elimination using the vaccine (with the assumed protective efficacy of %) is more promising in the states of new york and florida than nationwide (where much larger vaccination coverage will be needed to bring, and maintain, the control reproduction number, r c , to a value less than unity). simulations were also carried out to assess the impact of vaccine efficacy and coverage on this disease dynamics. this is done for the special case of the model in the absence of the use of masks in the public (i.e., the model ( . ) with c m = ε m = ). specifically, a contour plot of the control reproduction number (r c ) of the model, as a function of coverage (f v ) and vaccine efficacy (ε v ), is depicted in figure . this figure shows a decrease in the value of the reproduction number with increasing coverage and efficacy of the vaccine, as expected. for the assumed % efficacy of the hypothetical vaccine (i.e., ε v = . ) in table (a), the simulations depicted in figure (a) show that nationwide elimination of covid- can be achieved (i.e., r c can be brought to a value below unity) if at least % of the us populace is vaccinated. for the state of new york, it is shown that such elimination can also occur if the state-wide vaccination coverage is at least % (figure (b) ). similarly, figure (c) shows that the hypothetical anti-covid- vaccine can lead to the elimination of the pandemic from the state of florida if at least % of the residents of the state are vaccinated. the effect of the combined implementation of vaccination and social-distancing strategies, on the control reproduction number of the model ( . ), is also monitored (for the us and the two us states of new york and florida) by generating contour plots of r c , as a function of vaccine coverage and efficacy, for three levels (low, moder- for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . ate and high) of social-distancing effectiveness. the results obtained, depicted in figure , show that covid- elimination (measured in terms of bringing r c to a value less than unity) is feasible even if social-distancing is implemented at a low level of effectiveness (left panels of figure ). in particular, figure (a) shows that, with the assumed % efficacy of the vaccine, the implementation of social-distancing at low effectiveness level will lead to the elimination of covid- in the us if the nationwide vaccination coverage is at least %. this vaccination coverage needed to achieve such elimination decreases with increasing effectiveness of the social-distancing measures (figures (b) and (c) ). for the state of new york, for instance, vaccination program combined with social-distancing at low effectiveness level will lead to covid- elimination if at least % of the residents of the state are vaccinated (figure (b) ). the vaccination coverage needed for elimination decrease to % and %, respectively, if the social-distancing measures are implemented at moderate (figure (e)) and high ( figure (f)) effectiveness levels. finally, for the state of florida, combining vaccination with social-distancing at low effectiveness level will lead to covid- elimination in the state if at least % of the residents of the state are vaccinated (figure (g) ). the coverage needed for covid- elimination in florida decrease to % and %, respectively, for moderate (figure (h)) and high (figure (i)) effectiveness levels of the social-distancing strategy. additional numerical simulations were carried out to assess the community-wide impact of the combined impact of vaccination with a public mask use strategy (as measured in terms of reduction in the value of control reproduction number, r c ). the results obtained, depicted in figure , show a decrease in r c with increasing vaccine efficacy and compliance. for the fixed vaccine efficacy at %, the minimum vaccine coverage needed to eliminate covid- in the entire us if public mask use compliance is fixed at %, % and % is %, % and %, respectively (figures (a), (b) and (c)). similarly, covid- elimination can occur in the state of new york if the corresponding vaccine coverage are %, % and %, respectively (figures (d) , (e) and (f)). the numbers corresponding to elimination in the state of florida are %, % and %, respectively (figures (g) , (h) and (i)). thus, the simulations in figures and also emphasize the fact that the prospect of covid- elimination using a vaccine is greatly enhanced if the vaccination program is complemented with another public health intervention (such as social-distancing or the use of face masks in public), particularly if the complementary intervention is implemented at moderate or high effectiveness level. a novel coronavirus (covid- ) emerged in china in december . the virus, which is caused by sars-cov- , rapidly spread to over countries causing over million confirmed cases and , deaths globally (as of may , ) . although there are currently no safe and effective vaccine for use in humans, numerous concerted global efforts are underway aimed at developing such vaccine. in fact, a number of candidate vaccines are undergoing advanced stages of clinical trials. one of the most promising of these efforts is the candidate vaccine being developed by a research group at oxford university, which is expected to be available as early as january (or, latest, by the spring of ). we developed a mathematical model for assessing the the potential community-wide impact of a hypothetical imperfect vaccine against the covid- pandemic in the us. the model we developed, which takes the form of a deterministic system of nonlinear differential equations, was parametrized using covid- data for the entire us, as well as for the us states of new york and florida. the hypothetical vaccine was assumed to offer imperfect protective efficacy against the acquisition of covid- infection. the model we developed was rigorously analysed to gain insight into its dynamical features. these analyses reveal that the continuum of disease-free equilibria of the epidemic model is locally-asymptotically stable whenever a certain epidemiological threshold, known as the control reproduction number (denoted by r c ), is less than unity. the epidemiological implication of this result is that the covid- pandemic can be effectively controlled, whenever r c < , if the initial sizes of the sub-populations of the model are small enough. in other words, for this setting, the routine vaccination against covid- in the us can lead to the effective control of the pandemic if the efficacy and nationwide coverage of the hypothetical vaccine are high enough. in particular, if the vaccine efficacy and coverage are able to bring (and maintain) the reproduction number, r c , to a value less than unity. furthermore, threshold quantities for the community vaccine-induced herd immunity were calculated for the entire for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. table , with cm = εm = and various values of ξv. for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. table ? ? and in the absence of mask usage in public. (a) the entire us (b) the us state of new york (c) the us state of florida. parameter values used are as given in table with εm = cm = . us and for the states of new york and florida. we computed these thresholds for the case where social (physical)distancing is also implemented, and that the social-distancing is implemented at an effectiveness level that reduces the baseline values of the community contact rate parameters (β a and β s ) by %. our computations show, using the baseline values of the parameters of the model, that at least % of the entire us population needs to be vaccinated in order to achieve nationwide vaccine-derived herd immunity. similarly, at least % and % of the total susceptible population in the states of new york and florida, respectively, need to be vaccinated to achieve such herd immunity in the states. these vaccine coverage numbers are certainly on the high side, and may not be easily attained for so many reasons (ranging from the expected insufficient stockpile of the vaccine during the early stages of their deployment, general apathy towards vaccination and the sizable percentage of people that cannot be vaccinated for medical, personal and other reasons). our simulations showed that if the vaccination strategy is complemented with other public health interventions, such as a public mask use strategy for instance, the minimum herd immunity threshold required to effectively control the covid- pandemic significantly reduces to a more realistically-attainable level. for example, if vaccination (using a vaccine with the assumed efficacy of %) is combined with a public face mask strategy with % mask compliance nationwide, the herd immunity threshold for the entire us decreases from the % (for the mask-free scenario described above) to %. thus, the prospect of the effective control of covid- using routine vaccination is enhanced if it is combined with a public mass use strategy (especially if the effectiveness and coverage of the mask use strategy are high enough). we also carried out numerical simulations to measure the population-level impact of the rate at which the hypothetical vaccination is administered. the results obtained showed that the covid- burden (as measured in terms of daily and cumulative covid-induced mortality) decreases with increasing vaccination rate, as expected. our simulations showed that, while significantly high increases in the vaccination rate (from its baseline value) was necessarily needed to achieve significant reduction in disease burden in the entire us, a relatively small increase in the vaccination rate from its baseline value (as low as % increase) will be sufficient to lead to the effective control (or even elimination) of covid- pandemic in the states of new york and florida. in other words, the prospects of eliminating covid- , using the hypothetical vaccine, are more promising in the states of new york and florida, than nationwide (owing to the unrealistically high vaccine coverage needed to curtail or eliminate the pandemic in the latter). we also simulated the combined effect of implementing the routine vaccination program with social-distancing (in the absence of face mask usage). we showed that covid- can be effectively controlled using the two interventions even if the effectiveness level of social-distancing is low (as long as the vaccine coverage is high). in particular, our simulations showed that the control reproduction number (r c ) can be reduced to a value less than unity (needed for the effective control of the disease, in line with the local-asymptotic stability property of table . for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. various levels of mask compliance. (a) % mask compliance for the entire us (b) % mask compliance for the entire us (c) % mask compliance for the entire us (d) % mask compliance for the state of new york (e) % mask compliance for the state of new york (f) % mask compliance for the state of new york (g) % mask compliance for the state of florida (h) % mask compliance for the state of florida (i) % mask compliance for the state of florida. parameter values used are as given in table with various values of cm . for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . the continuum of disease-free equilibria, established in section ). for example, we showed that for low, moderate and high effectiveness levels for the social-distancing strategy implemented in the state of new york, covid- elimination is feasible if the vaccine coverage is at least %, % and %, respectively (the corresponding figures for the us state of florida are %, % and %). thus, these figures suggest that covid- elimination (using the combined vaccination and social-distancing strategy) is more likely in the us state of florida, followed by the us of state of new york and then nationwide. we assessed the population-level impact of combining the routine vaccination strategy with a public mask use strategy. our simulations show a decrease in the burden of the covid- pandemic (again as measured in terms of reduction in the value of the reproduction number r c ) with increasing efficacies and compliance of the vaccine and mask usage. it was shown that, for the case of the entire us, if the vaccine efficacy is fixed at the assumed % and mask compliance is fixed at the low value of %, covid- can be eliminated in the us if the vaccine coverage is at least %. the vaccine coverage decreases to % and %, respectively, if mask use compliance is increased to % and % nationwide (the numbers for us state of new york, corresponding to the aforementioned mask use coverage are %, % and %, respectively; similarly, the numbers for the us state of florida are %, % and %, respectively). again, these result confirmed that covid- elimination is more feasible is vaccination is combined with another intervention (mask use in public, in this case), and that such elimination is more easily attainable in the us states of new york and florida than nationwide. in summary, this study shows that the prospect of effectively controlling covid- in the states of new york and florida, as well as nationwide, is promising using the hypothetical imperfect anti-covid- vaccine. the prospect of such effective control and/or elimination is greatly enhanced if vaccination is combined with other interventions that limit community transmission, such as social-distancing and mask use in public. furthermore, elimination is more likely to be achieved using a vaccine in the states of new york and florida than nationwide (since the latter requires much higher, and probably realistically-unattainable, vaccination coverage to achieve elimination). for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint coronavirus disease (covid- ) technical guidance emergencies, preparedness, response. pneumonia of unknown origin -china online version early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the novel coronavirus online version more coronavirus vaccines and treatments move toward human trials online version world health organization jobless rate may soar to % stop covid or save the economy? we can do both impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand to mask or not to mask: modeling the potential for face mask use by the general public to curtail the covid- pandemic scores of coronavirus vaccines are in competition -how will scientists choose the best?" a natureresearch journal (assessed on in race for a coronavirus vaccine, an oxford group leaps ahead online version transmission potential of the novel coronavirus (covid- ) onboard the diamond princess cruises ship feasibility of controlling covid- outbreaks by isolation of cases and contacts early dynamics of transmission and control of covid- : a mathematical modelling study reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission on the definition and the computation of the basic reproduction ratio r in models for infectious diseases in heterogeneous populations an interactive web-based dashboard to track covid- in real time coronavirus covid- global cases by johns hopkins csse online version coronavirus disease (covid- ) situation reports national center for immunization and respiratory diseases (ncird), division of viral diseases testing the efficacy of homemade masks: would they protect in an influenza pandemic the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (sars-cov ) estimates of the severity of coronavirus disease : a model-based analysis public health responses to covid- outbreaks on cruise ships-worldwide clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study estimation of the transmission risk of the -ncov and its implication for public health interventions vaccination and herd immunity to infectious diseases the concept of herd immunity and the design of community-based immunization programmes is sweden doing it right? one of the authors (abg) acknowledge the support, in part, of the simons foundation (award # ) and the national science foundation (award # ). cnn acknowledges the support of the simons foundation (award # ). key: cord- - nkrh authors: bernards, nick; campbell‐verduyn, malcolm; rodima‐taylor, daivi; duberry, jerome; dupont, quinn; dimmelmeier, andreas; huetten, moritz; mahrenbach, laura c.; porter, tony; reinsberg, bernhard title: interrogating technology‐led experiments in sustainability governance date: - - journal: glob policy doi: . / - . sha: doc_id: cord_uid: nkrh solutions to global sustainability challenges are increasingly technology‐intensive. yet, technologies are neither developed nor applied to governance problems in a socio‐political vacuum. despite aspirations to provide novel solutions to current sustainability governance challenges, many technology‐centred projects, pilots and plans remain implicated in longer‐standing global governance trends shaping the possibilities for success in often under‐recognized ways. this article identifies three overlapping contexts within which technology‐led efforts to address sustainability challenges are evolving, highlighting the growing roles of: ( ) private actors; ( ) experimentalism; and ( ) informality. the confluence of these interconnected trends illuminates an important yet often under‐recognized paradox: that the use of technology in multi‐stakeholder initiatives tends to reduce rather than expand the set of actors, enhancing instead of reducing challenges to participation and transparency, and reinforcing rather than transforming existing forms of power relations. without recognizing and attempting to address these limits, technology‐led multi‐stakeholder initiatives will remain less effective in addressing the complexity and uncertainty surrounding global sustainability governance. we provide pathways for interrogating the ways that novel technologies are being harnessed to address long‐standing global sustainability issues in manners that foreground key ethical, social and political considerations and the contexts in which they are evolving. digital technologies in sustainability governance: possibilities, politics, power efforts to harness emerging technologies to address a host of new and longer-standing sustainability challenges have recently proliferated. artificial intelligence (ai), blockchain, big data and other new technologies are central to a growing number of on-going experiments, ranging from the tracking of greenhouse emissions to monitoring wildlife poaching and global supply chains, to transnational efforts to combat human trafficking, and manage the covid- pandemic. these unfolding experiments seek to mobilize digital technologies to meet a growing range of governance challenges that are typically grouped together under the banner of sustainability and sustainable development. these developments have not, however, been much interrogated in international relations and global governance scholarship (though see boersma and nolan, ; duberry, ; gale, ascui, and lovell, ) . existing policy and practitioner debates, meanwhile, tend to emphasize the affordances and pathologies of specific digital technologies (beaumier et al., ) . a number of important questions have thus remained unaddressed: how do unfolding initiatives centred on ai, blockchains, big data and other emerging technologies seek to overcome, or extend and reinforce, the limits of existing global governance? what debates and conflicts of interest are elided by appeals to technological applications as solutions to governance challenges? how does the development and deployment of new technologies intersect with existing disparities of power, resources, and access? this article begins to address these questions, synthesizing discussions an interdisciplinary workshop on these themes held at the university of warwick in december . we situate on-going technology-led experiments in sustainability governance within three longer-standing global trends: ( ) a growing reliance on private, voluntary codes of conduct, standards, and third-party auditing; ( ) global experimentalist governance; and ( ) efforts to adapt governance mechanisms to deal with the growing prevalence of informal and illicit economies. in light of this, we argue that uses of technology in multi-stakeholder initiatives have tended to reduce rather the scope for participation in sustainability governance, deepen challenges to participation and transparency, and reinforce rather than transform existing power relations. in what follows, we outline the above three global governance trends in turn, tracing their intersections with emerging technology-centred initiatives in global sustainability governance. we then conclude by outlining a number of questions for scholars, practitioners and policy makers to consider in interrogating the uses of technology in sustainability governance. technology-centred initiatives to improve global sustainability governance are in many ways extensions of the patchwork of private codes of conducts and corporate social responsibility (csr) policies developed in recent decades. the inability of these corporate-led modes of 'responsible governance' to yield significant improvements for workers and the planet is well-documented (fransen and burgoon, ; koenig-archibugi, ; lebaron, lister and dauvergne, ) . such initiatives have frequently resulted in mere 'corporate philanthropy' that favours powerful stakeholders over grassroots communities (orock, ) . these modes of governance have often reinforced existing inequalities. for example, corporate codes of conduct for worker safety in garment supply chains have been found to pass costs of compliance on to supplier factories. yet, they do little to alleviate the time and cost pressures placed on suppliers by major branded buyers, who often drive unsafe working conditions in the first place (scheper, ; taylor, ) . recent responses to these failures increasingly rely new technologies. big data and blockchain technologies, for example, are increasingly instrumental to a growing range of 'multi-stakeholder' arrangements between private forprofit firms and public bodies seeking, for instance, to protect working conditions or to trace and disclose greenhouse gas emissions and 'conflict minerals' across global supply chains. these experiments are being developed and applied in ways that reinforce existing patterns of governance and relations of power. novel technologies are being integrated into the longstanding practices of private professional service firms in monitoring sustainability across global supply chains. previous research shows how the 'big four' professional services firms (kpmg, pwc, deloitte, and ey) firms play a significant and growing role in shaping private supply chain governance (fransen and lebaron, ) . the big four, along with smaller audit firms and consultancies (e.g. rcs global) increasingly promote blockchains as means of improving the effectiveness of supply chain governance. blockchain delivers a record of the origin and journey of the raw materials, which is accessible to all relevant parties yet not manipulable by any single 'node' in the shared digital network. in so doing, blockchains can establish a community of participants and an authoritative record of provenance, and by moving confidential data freely between trading partners, could enhance transparency and accountability. yet, these developments leave supply chain governance dominated by lead firms, often working with the 'big four' and more specialized supply chain management consultants. the entities developing and supporting such technology-led projects are frequently the same ones involved in existing global supply chain governance. the prominent roles of audit firms and private sector consultants in developing technological solutions to global sustainability governance challenges raise important issues. the profit models of such firms rest primarily on service fees. there is a danger that private actors' profit incentives could further fragment standards and enforcement across the proliferating range of 'sustainability services'. competition for clients threatens to produce a 'race to the bottom' of the kind seen among credit ratings agencies in the build-up to the global financial crisis (kruck, ) . equally, such initiatives provide no new standards or enforcement mechanisms and remain reliant on existing forms of factory-, farm-, or mine-level monitoring. in the words of a manager at one blockchain-based audit start-up: a blockchain will record an immutable record of custody of a material, the locations it's traveled through, its composition over time, and all that . . . but if you're trying to make sure the wrong material never enters the system in the first place, you need processes to make this work. (hyperledger n.d., p. ) . in brief, blockchain applications for supply chain governance leave market-based forms of governance rooted in 'disclosure' and soft standards largely intact, both in terms of the actors involved and the standards being enforced. we can see similar issues at stake if we move from supply chain governance to new methods of 'greening' financial markets, another key area where experiments with new technologies are underway. environmental, social and governance (esg) investment and esg ratings have grown rapidly as big data and other technologies have enabled investors to quantify hard-to-measure socio-political variables. yet, standards for what counts as 'sustainable' still vary. earlier accounting frameworks related to csrincluding the global reporting initiative and the carbon disclosure projecthave been accused of providing an 'alphabet soup' of poorly-correlated indicators (imf, ). more recent industry-led efforts like the taskforce for climate-related financial disclosures (tcfd) are somewhat better. the tcfd has departed from earlier csr definitions of sustainability by only including 'financial material' esg issues. led by bank of america chief executive and working closely with the big four accounting firms, the world economic forum (wef) has initiated a framework to standardize esg metrics and link them to the un's sdgs (naumann and temple west, ) . debates over applications of new technologies in sustainability governance need to be situated within these exercises in classification and standardization regarding what qualifies as 'sustainable'. the eu taxonomy, for instance, has been linked to a green-supporting or brown-penalizing factor for capital requirements (fleming and brunsden, ) . more encompassing policies like 'green quantitative easing' suggested by central banks can only become feasible once consensual definitions of green or brown investing are established. put differently, to realize the potential of technologies, we must first bring the context of private governance to the forefront of discussions about which technologies can and should be used, as well as for which purposes. the manners in which technology-led experiments in global sustainability governance foreground private over public was also illustrated in many of the immediate responses to the covid- pandemic. the world health organization, for instance, began coordinating a blockchain-based data storage and communication platform to address the surge in cyber attacks and mis-information during what it described as the related 'infodemic'. the platform, mipasa, is built on hyperledger fabric a permissioned (e.g. private) blockchain originally built by ibm and whose governing board consists of representatives of large technology (e.g. hitachi, intel, oracle, microsoft), finance (american express, bbva, jp morgan chase), professional services firms (accenture) and other mncs (daimler). beyond blockchain projects, the wider trend towards reliance on private, individual deployment novel technologies in global sustainability governance was prominently encapsulated in the strategic partnership framework agreement signed between the un and wef in for 'accelerating the implementation of the sustainable development goals' (wef, ). the first key focus area of this public-private partnership is harnessing the 'potential of financial innovation, new technologies and digitalisation to increase financing for the sdgs' (wef, ). in sum, technology-centred arrangements may tend to perpetuate and even expand the roles of private actors in sustainability governance, while potentially deepening the pathologies of existing forms of private governance. as we argue further in the next section, these tendencies are reinforced by a parallel trend of experimentalism in global governance. despite the considerable hype surrounding them, applications of emerging technologies in sustainability governance remain very much provisional and experimental. it is thus useful to consider such initiatives in relation to on-going trends towards experimentalist forms of global governance. experimentalist governance involves the setting of goals, trialling of multiple policy measures, continuous monitoring of progress through quantitative indicators, and revision based on rigorous peer review (sabel and zeitlin, ) . unlike centrally defined and potentially more static forms of management, such looser and 'provisional' governance forms can promote the flexible arrangements necessary to respond to sustainability challenges in environments of uncertainty (best, ) . while academic literature on experimentalist governance originated in the study of devolved responses for addressing common concerns in the european union (sabel and zeitlin, ) , wider forms of 'global experimentalism' have recently been outlined (de b urca et al., ; nance and cottrell, ) . to date, these studies have provided little consideration of the role of technologies in private-led patterns of global governance (armeni, ; campbell-verduyn and porter, ) . this can overlap with the forms of private governance discussed aboveprivate authorities can rely on experimentalist modes of governance (see brassett et al., ) . the distinction is essentially that, in referring to 'private' governance, the concern is with who is doing the governing, while references to 'experimentalist' modes of governance are more about how governance is done. critically, engagements both by public and private actors with blockchain, ai, and other emerging technologies are notably experimentalist in character. one example here is in the area of development aid. there are theoretical elaborations on potential applications of blockchain to development aid effectiveness, highlighting the potential of transparent and immutable ledgers to enhance the credibility of policy commitments or address verification problems (e.g. reinsberg, ) . actual policy interventions using these technologies, though, have generally taken precisely the form of trialling multiple measures, measuring outcomes, and constant revision. one notable example here is the german gesellschaft f€ ur internationale zusammenarbeit's (giz) 'blockchain lab', which sponsors and organizes pilot projects by public and private actors using blockchain to address challenges directly relating to the sdgs. bottom-up, less hierarchical forms of experimentalist governance enabled by new technologies, could in theory enrich sustainability governance by inviting participation from local actors. linders ( , p. ) , for instance, writes about potential open data platforms for developing countries to generate a 'sort of tripadvisor or yelp for aid' that can encourage local accountability of technology-enhanced programs. in practice, experimentalism's tendency to also offer highly technical solutions may deepen barriers to participation. experimentalist decision-making often draws heavily on calculative rationalities derived from financial accounting in order to accurately compare the results of the diverse approaches employed to achieve common goals. in their focus on measuring and auditing performance, these rationalities often recast governance as merely a technical and administrative matter. this diminishes the role and input of local knowledge (shore and wright, ; strathern, ) . likewise, the growing technology-intensiveness of experimentalist governance narrows the range of non-state actors able to participate in public-private partnerships. it is primarily private companies and the largest ingos that have the resources to create and manipulate the technologies at the heart of novel solutions to global sustainability challenges (duberry, ) . consequently, smaller and more local actors, in particular from the global south, may be left out, entrenching existing disparities in access and participation. moreover, these disparities may well be amplified as large technology firms seek to maximize both data collection and possession. private companies' access to a growing amount and diversity of data can thus shape agendas in ways that favour particularistic over collective concerns (arora, ) . for example, governments face domestic political pressures and economic challenges that open up space for internationally-coordinated, experimentalist governance of the digital economy. the un's global pulse programme connects academics, private and government actors and un personnel to generate 'actionable' insights about how big data can facilitate sustainable development. but global pulse projects in practice are dominated by private businesses and governments, with relatively limited possibilities for the involvement of csos. likewise, geopolitical competition among data powers, such as china, the us and the eu, can encourage domestic experimentalist governance innovations, as these states seek to enhance and secure their own digital capabilities (mahrenbach and mayer, ) . one prominent example is china's great firewall, which simultaneously cleared the path for ground-breaking research and industrial development of ai and made it more difficult for non-chinese businesses to operate in china (aaronson and leblond, ) . diverse government incentives thus encourage experimentalist governance in the digital economy as a means of achieving preferred outcomes, while reinforcing patterns of political power and participation that may tend towards particularistic rather than collective gains. the crucial roles of large technology firms in sustainability experiments could enable them to define the agendas and goals pursued. the competing pressures faced by governments seeking to both expand their own gains from the digital economy and to use modern technologies further complicate the benefits of experimentalism. finally, efforts to apply new technologies to sustainability challenges have very frequently been driven by efforts to grapple with the growing prevalence of informal economies. here, our concern is with who and what are being governed. economic informality in this sense has been an important, cross-cutting concern in sustainable development policy in recent decades (see bernards, ; phillips, ; rodima-taylor, ; taylor, ) . informality refers to the activities and actors that operate outside the regulations and laws of the modern economy (loayza, ). informal actors who usually represent marginal populations and groups are not able to fully benefit from public services or formal sector protection and risk mitigation, while also not able to contribute to the creation of public goods through taxation and other mechanisms. at the same time, informal sector enterprises may benefit from greater flexibility and dynamism of their activities as well as serve as a source of employment for marginal populations during economic down-turns (loayza, ). the dynamics of local informality are intricate, yet better attempts need to be made to understand the contexts in which many technology-led sustainability governance initiatives are ultimately grounded. localized informal practices are wrapped up in global value chains, for instance, through casualized labour in agriculture or outsourcing in clothing production. these present particular governance challenges around labour rights and environmental standards (meagher, ) . technological applications in sustainability governance are often aimed at making informal or illicit economies 'legible' both to regulators and to global capital. muirhead and porter ( ) argue that the 'traceability systems' enabled by new digital technologies for tracking the cross-border travel of an increasingly diverse range of objectsincluding conflict minerals, pharmaceuticals, carbon emissions, and money launderingform complex, heterogenous constellations between the physical properties of the objects being traced and the networks and infrastructures used for their management. by enabling clearer visibility and authentication of objectsincluding intangible onestraceability systems can, in some instances, help reduce areas of informal or illicit activity. new technologies may render human trafficking more visible and governable (e.g. by tracking illegal financial transactions), broaden awareness of victims' plight and facilitate networking between law enforcement and non-state organizations combatting human trafficking. an example here is the global emancipation network which brings together technology partners such as microsoft, splunk, deep vision ai and others with law enforcement, anti-trafficking non-profits, and businesses in hospitality, finance and transportation to deploy advanced data analytics to make human trafficking more visible as a means of helping to stop it. once again, there are important tradeoffs. rendering local actors 'legible' through technological means in the context of global supply chains dominated by distant lead firms or development projects by metropolitan donors can result in the imposition of external, pre-determined criteria on local spaces and practices. this interplay of informal activities with efforts to promote sustainability through formalization, transparency, and traceability, in turn, has significant, if ambiguous, implications for livelihoods. efforts to govern artisanal mining are a notable example (vogel et al., ) , as are conservation measures (witter and satterfield, ) , both of which are prone to excluding local populations. technological applications can exacerbate these dynamics, particularly where they double down on the weaknesses of market-led forms of supply chain governance discussed above. for example, there has been a recent flurry of blockchain applications for preventing child labour in cobalt mining in the democratic republic of the congo, as demand for cobalt (a key component of batteries for electric cars and portable electronics) has surged in recent years (e.g. lewis, ) . most of these programmes aim to prevent child labour by reliably certifying that cobalt has been mined from specific industrial installations rather than from artisanal mines, where most child labour takes place. even if it were to eliminate child labour from global supply chains, displacing artisanal mining with industrial mining would likely have ambiguous livelihood consequences for mining communities at best. recent research has highlighted, for instance, growing evidence of labour market segmentation, including a preference for expat workers in industrial mining, as well as limited wage gains for workers moving from artisanal to industrial mining in the copperbelt, driving a rise in inequality in the region (radley, ; rubbers, ) . there are serious questions here that need to be raised about the kinds of risks, and for whom, new technologies might be used to mitigate. in sum, technological solutions to sustainability issues often boil down to attempts to render complex and geographically dispersed informal spheres of activity 'legible' and traceable. such transparency efforts have important, yet often underexplored, implications. on the input-side, early processes of technological development and application can be hampered by significant disparities in access to material resources and representation that underpin digital and socio-economic divides. on the output side, transparency provided in evolving technological experiments is geared to the investment decision matrices of financiers, to the regulatory compliance mandates of governments, and to end consumers. policy making and broader public discussion over the integration of emerging technologies such as artificial intelligence, big data, and blockchain into global sustainability governance need to be far more socially and politically sensitive than is currently the case. recognizing and overcoming these issues is particularly important now as these and other technologies are also being foregrounded in transnational efforts to secure global supply chains and other responses to the covid- pandemic. digital technologies being applied in complex and evolving environments both shape and are shaped by diverse human, material, and normative elements (bernards and campbell-verduyn, ) . heterogenous assemblages combine local inventive practices and cultural repertoires related to new technology solutions with old and new infrastructural pipelines and institutional actors (rodima- taylor and grimes, ) . the integration of new technologies into multi-stakeholder efforts to address sustainability challenges must be understood within the longer-standing patterns of private authority, experimentalism, and struggles to cope with informal economies in global governance. by way of conclusion, we highlight a number of areas of concern that must become central to discussion, analysis and implementation of technology-led initiatives in global sustainability governance. these questions are crucial if we are to avoid extending well-known problems in attempting to address global sustainability governance challenges. unfolding technological experiments do, of course, hold some promise, and constitute quite a wide terrain. they thus need to be assessed on a case-by-case basis. yet, such assessments can collectively consider important but often backgrounded social, political, and economic relations through which new technologies are being developed and into which they are deployed: first and foremost, attention must be given to what new technologies cannot do. technologies cannot solve problems that are social and political at the roota point underlined in our discussion above. many sustainability governance problems concern politics and power. three guiding questions can encourage a systematic approach to overcome contextual hindrances in employing technology to actualize sustainability goals: whose problems are new for instance, probabilistic means of detecting likely human trafficking victims through ai applications might be helpful in separating out forced and exploitative forms of mobility from benign ones. however, identifying victims alone is not enough to resolve the knot of issues shaping and driving human trafficking. ais cannot say what should happen after victims of trafficking are located, or resolve the underlying conditions which facilitate trafficking in the first place. without substantive attention to victims' rights and the overall institutional environment of reinforcing these rights, detection of trafficked people might even render victims susceptible in new ways (e.g. to securitized and criminalized systems of border enforcement). we have argued that experimentalist modes of technologydriven sustainability governance can facilitate the introduction of novel intermediaries and brokers, while also entrenching the roles of existing actors. many of the latter actors are private parties, such as audit and consulting companies; many of the former are new tech firms. moreover, fluid areas of activity enabled via new connective technologies bring together a variety of formal and informal actors. as we have noted in the discussions of informality and experimentalism above, these developments are creating new political spaces, which can deepen old forms of exclusion and uneven access to participation. for example, the private firms involved in esg have a potential to promote industry-driven visions of future research and development in environmental governance. these activities can also create new global publics through awareness-raising and lobbying, and define what 'count' as global sustainable practices. there is a need to recognize the costs of accessing these new quasi-public spaces, which can threaten to reinforce existing inequalities and divides. the resources and roles of large, well-funded international non-state organizations in developing ai applications in environmental conservation, and the comparatively limited scope for participation by affected communities, are notable examples here. the new technologies increasingly used in sustainability governance are accompanied by security implications, particularly regarding privacy, which are often not been adequately addressed in extant debates. security technologies are fundamentally 'sites of experimentation', enmeshed in both ethical and practical dilemmas (bosma, , p. ) . the inner workings of technologies have remained opaque 'black boxes' to many, if not most, stakeholders on grounds of security or economic competitiveness. to ensure then that local voicesparticularly those of affected communitiesremain at the forefront of technology-enhanced sustainability governance activities, we suggest the following guiding questions. first, what kinds of actors are new technologies actually (dis)empowering? second, what kinds of exclusions or inequalities might be reinforced and/or created through technology-centred governance processes? we have situated technology-led sustainability governance initiatives in the concomitant rise of private, voluntary codes and standards. we equally illustrated how experimentalist modes of decision-making that may extend standardized accounting practices and calculative rationales across diverse forms of sustainability governance might do so at the cost of local spaces and practices. the result of merging these 'human accounting' protocols and techniques of financial accounting with those of socio-economic management can be a prioritization of short-term profit maximization and financial markets' agendas over longer-term sustainability needs. in recasting governance as a technical and administrative affair, sustainability accounting can minimize opportunities for and contributions from local actors and knowledge, respectively. soft-law governance approachesfrom emerging esg standards to labour codesexacerbate these issues, being both difficult to challenge in case of disputes and posing barriers to binding public regulation or independent civil society monitoring. these insights should focus attention on the need to interrogate the kinds of transparency and accountability sought in advancing common templates across diverse and informal communities. in seeking to render 'legible' activities in grassroots communities, private-driven sustainable governance initiatives may paradoxically by-pass the roles and needs of key local mediators. bottom-up forms of 'everyday experimentation' and 'frugal innovation' at the grassroots level can be crucial to addressing sustainability issues, yet are often overlooked or marginalized in many current applications (altamirano and van beers, ; leliveld and knorringa, ) . ethical technology standards and frameworks must be developed in collaboration with local communities and stakeholders and by considering local norms and morals. several guiding questions can help systematize this process of interrogation. first, what kinds of transparency and accountability are promoted by applications of new technologies? and, second, who benefits from the forms of accountability that are pursued in specific sustainability governance efforts? asking 'big' questions on the need for participatory and accountable frameworks we have argued that private-led environmental and sustainability initiatives have a potential to reinforce power imbalances and exclusion when interacting with communities and institutional actors in the global south. this is because the use and development of new technological solutions interacts with formal and informal, local and geopolitical agendas and interests. the incomplete nature of frameworks and standards governing new digital technologies can do little to ameliorate these issues. here again, we need local-specific, participatory development of accountability standards and frameworks in sustainability governance, in particular standards that embody local norms and morals. from this perspective, stressing the novelty of technological solutions for complex and evolving sustainability challenges can distract from the larger structural issues in which such governance is embedded. helpful guiding questions here include: what kinds of end-goals should sustainability governance initiatives consider, and for whom? what kinds of sustainability are emphasized in discoursesclimate risk, environmental risks, human/labour rights, or others? what political and moral assumptions are bundled into technological applications and their use? who has access to 'sustech' applications and the capacity to use them? and are such solutions creating new digital divides? in the current environments of high complexity and uncertainty surrounding sustainable governance initiatives, we argue that ethical, social and political considerations should be given foremost priority. this article has situated the novelty of new technologies in three wider trends to provide pathways for directing attention beyond mere technical considerations. there is undoubtedly room for these and other technological initiatives to be grounded in further trends. we expect that doing so will raise a host of other questions pertaining to the evolving roles of technologies in sustainability governance. we look forward to engaging with themand encourage public and private actors central to sustainability governance to do the same. may ]. . we are focused primarily in this section on efforts to govern informal economies, rather than informality in governance itself, though the latter is undoubtedly important in governing a number of policy areas relevant to sustainability and technology (morin et al. ). . https://www.globalemancipation.ngo/global-emancipation-networkmission-offerings/ [accessed may ]. . by the 'usual suspects' noted above such as the big four professional services firms (deloitte ), the wef (liao ), but also scholars (mashamba-thompson and crayton ) who "recommend a low cost blockchain and artificial intelligence-coupled self-testing and tracking systems for covid- and other emerging infectious diseases" in sub-saharan africa. international organization at the university of groningen. his research combines a general focus on ideas and materiality with a specific interest in the roles of non-state actors, technologies and technical artefacts in contemporary global governance. daivi rodima-taylor is a social anthropologist and researcher at the african studies center of boston university, and visiting researcher at the university of california, irvine. she has taught anthropology and international relations and engaged in longitudinal ethnographic fieldwork in african communities. her current research focuses on the intersection of grassroots economies and information technology. jerome duberry is a research associate at the albert hirschman center on democracy, graduate institute geneva. his research activities focus on the use of emerging technologies to support nature conservation and foster political 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mozambique's limpopo national park nick bernards is assistant professor of global sustainable development at the university of warwick. his research focuses on the political economy of irregular work, technology, and poverty finance.malcolm campbell-verduyn is assistant professor of international political economy in the department of international relations and key: cord- -maym iah authors: rogala, anna; szczepaniak, maria; michalak, natalia; andersson, gerhard title: internet-based self-help intervention aimed at increasing social self-efficacy among internal migrants in poland: study protocol for a randomized controlled trial date: - - journal: internet interv doi: . /j.invent. . sha: doc_id: cord_uid: maym iah background: migration is a challenging life transition that may be a source of various problems related to well-being and mental health. however, the psychological adaptation of migrants may be potentially facilitated by social self-efficacy—the beliefs in one's ability to initiate and maintain interpersonal relationships. previous research suggests that social self-efficacy is positively related to adjustment and negatively related to loneliness, depression, and psychological distress. research also confirms that self-efficacy beliefs can be effectively enhanced using internet-based interventions. these results served as a background for creating the new in town, a self-help internet-based intervention for internal migrants in poland that aims at increasing social self-efficacy. exercises in the intervention are based on the principles of cognitive behavioral therapy and relate to sources of self-efficacy beliefs: mastery experiences, vicarious experiences, verbal persuasions, and emotional and physiological states. users complete increasingly challenging tasks that encourage them to interact with their environment. the aim of this trial was to investigate the efficacy of the new in town intervention. methods: the efficacy of the new in town intervention will be tested in a two-arm randomized controlled trial with a waitlist control group. social self-efficacy will be the primary outcome. secondary outcomes will include loneliness, perceived social support, and satisfaction with life. additionally, we will measure user experience among participants allocated to the experimental group. we aim to recruit a total of n = participants aged at least years who have changed their place of residence in the last months and have an internet connection. participants will be assessed at baseline, -week post-test, and -week follow-up. discussion: the trial will provide insights into the efficacy of internet-based self-help interventions in increasing social self-efficacy. given that the intervention works, new in town could provide an easily accessible support option for internal migrants in poland. trial registration: the trial was registered with clinicaltrials.gov (identifier: nct ) on th september . internet-based self-help intervention aimed at increasing social self-efficacy among internal migrants in poland: study protocol for a randomized controlled trial the number of migrants worldwide has been growing rapidly over the past years [ ] . most of them migrate inside their own country [ ] . according to the estimations of the united nations development programme, in there were million internal migrants worldwide, compared to million international migrants [ ] . king and skeldon [ ] suggest that "the age of migration is therefore also an age of mass internal migration" (p. ). migration-both internal and international-is a source of potential specific stressors that could threaten migrants' well-being and mental health, e.g., communication difficulties, cultural differences, socioeconomic as well as employment status change [ ] . it is also a challenging life transition that may be related to problems in the social area. research has shown that students and visiting scholars from china in canada report more communication problems, difficulties in making friendships, loneliness, and lower subjective adaptation, compared to non-chinese canadian and chinese-canadian students [ ] . research also suggests that depression symptoms are more prevalent among internal migrants in china compared to the general population [ ] . what is more, internal migrant adolescents report lower levels of self-esteem, higher levels of depression, and have less social connections than local adolescents [ ] . however, psychological adaptation of migrants may be facilitated by personal resources, such as self-efficacy beliefs [ ] . social cognitive theory [ ] defines selfefficacy as ''belief in one's capabilities to organize and execute the course of action required to produce given attainments''(p. ). self-efficacy has been shown to be one of the important factors that help an individual to deal with stressful life transitions and adjust to a new situation [ ] . maciejewski, prigerson, and mazure [ ] found that self-efficacy mediates the j o u r n a l p r e -p r o o f relationship between dependent stressful life events and symptoms of depression among americans with a prior history of depression. moving to a new residence (internal migration) was the most often reported life event in the aforementioned study (n = ), along with serious financial problems (n = ) and life-threatening illness or injury (n = ) [ ] . jerusalem and mittag [ ] suggested that "within this stressful transitional adaptation to the new societal living conditions, self-efficacy can function as a personal resource protecting against deleterious experiences, negative emotions, and health impairment" (p. ). numerous studies have confirmed the positive effects of self-efficacy beliefs among migrants. research on young east german migrants suggests that individuals high in selfefficacy perceive changes in their lives more as challenges and less as threats, and report lower anxiety and better health than migrants low in self-efficacy [ ] . american expatriates in europe with high levels of self-efficacy express greater degrees of cultural adjustment than those with low levels [ ] . wang and sangalang [ ] found that among filipino immigrant employees in canada self-efficacy is positively related to work adjustment. a study among afghan and kurdish refugees in new zealand and australia showed that self-efficacy beliefs were associated with higher subjective well-being and lower psychological distress [ ] . selfefficacy was also found to be a predictor of mental health among malawian returning refugees [ ] . moreover, research among somali adolescents resettled in the united states suggests that self-efficacy is positively related to a sense of school belonging and negatively to ptsd and depression symptoms [ ] . not only self-efficacy beliefs but also social support from friends and significant others is positively related to psychological adjustment [ ] and subjective well-being of migrants [ ] . therefore, the constitution of a new social network is very important for this population. there is one type of self-efficacy beliefs that may especially help migrants to establish new social bonds-social self-efficacy [ ] . although self-efficacy can be defined j o u r n a l p r e -p r o o f [ ] more globally as a "traitlike general sense of confidence in one's own capabilities to master different types of environmental demands" (p. ), it is usually conceptualized as a context-specific construct [ ] [ ] . research suggests that using domain-specific self-efficacy measures allows predicting the outcomes more successfully [ ] . social self-efficacy beliefs can be defined as [ ] "confidence in one's ability to engage in the social interactional tasks necessary to initiate and maintain interpersonal relationships in social life and career activities" (p. ). research has shown that social self-efficacy is negatively correlated with attachment anxiety, depression, and loneliness among internal migrants in the usafreshman college students [ ] . in addition, social self-efficacy mediates the relationship between attachment anxiety and loneliness [ ] . social self-efficacy is also negatively related to acculturative stress, depression, and self-concealment among international college students in the united states [ ] . fan and mak [ ] found that first-generation migrant students in australia reported lower social self-efficacy than second-generation ones. they also reported more social difficulties and fewer shared interests with people in the host society, compared to second-generation migrant students [ ] . international students in canada also reported lower levels of social self-efficacy than canadian and secondgeneration migrant students. moreover, their low self-efficacy predicted low academic satisfaction and high psychological distress [ ] . similar results were obtained in australia-chinese migrant and overseas students reported lower self-efficacy than anglo-australian and second-generation migrant students from southern europe. social self-efficacy was also positively related to academic satisfaction and negatively to psychological distress. overall, the results of the aforementioned study suggest that social relationship issues impact the academic satisfaction of overseas students and migrants to a greater extent than the satisfaction of non-migrant students [ ] . therefore, it may be concluded that social selfefficacy is potentially beneficial for the psychological adjustment of migrants helping them j o u r n a l p r e -p r o o f establish new connections in the social environment. however, most evidence for the positive effects of social self-efficacy is derived from non-experimental research. our study addresses this gap. not only social self-efficacy, but also other factors, such as age, gender, educational level, and occupational background, socio-economic position, and availability of social support are related to adjustment and well-being of migrants [ ] [ ] . however, not all of these factors can be easily changed. on the other hand, self-efficacy beliefs in various domains, including initiating and maintaining interpersonal relationships, are malleable and can be intentionally enhanced [ ] . in line with bandura's social cognitive theory [ ] , selfefficacy beliefs can be altered by interpreting information from four different sources. first, perceived as the most powerful is mastery experience rooted in the interpretation of one's own performance in a specific domain as successful. second, the vicarious experience is related to observing the accomplishments of others which can be interpreted as a proof of specific goals attainability. encouraging feedback about one's own skills, abilities or performance given by significant others serve as a third source of self-efficacy beliefs, verbal and social persuasion. psychological and emotional states are the fourth source. individuals treat their emotional and physiological reactions like stress or anxiety while performing particular tasks as indicators of their capabilities [ ] . bandura's theoretical framework found support in empirical research results [ ] [ ] . therefore, we can distinguish not only theoretically but also empirically the aforementioned sources in the context of social selfefficacy beliefs [ ] . furthermore, previous research showed that an internet-based intervention drawn upon social cognitive theory could be an effective means of self-efficacy beliefs reinforcement [ ] . human services professionals exposed to indirect trauma who took part in an internet-based intervention displayed significantly greater improvements in self-j o u r n a l p r e -p r o o f efficacy beliefs related to managing secondary traumatic stress compared to an active control group. the internet-based sessions included modules focused on recalling past personal successes, the cognitive reappraisal of situations perceived as failures, an individually tailored plan of boosting self-efficacy beliefs and positive thoughts, and emotions reinforcement [ ] . internet-based interventions are a promising approach to reinforcing the self-efficacy of participants in a variety of specific contexts. teachers who accomplished an internet-based problem-solving training displayed significantly greater improvements in general and work-specific self-efficacy compared to waitlist control group members [ ] . an online positive psychology intervention to promote positive emotions, self-efficacy, and engagement at work consisting of modules targeting happiness, goal setting, and resource building, has shown its positive impact on participants' self-efficacy [ ] . the web-based intervention aimed at promoting healthy eating has proven its effectiveness in enhancing selfefficacy for total dairy intake among college students [ ] . moreover, the internet-based program aimed at reducing cannabis use has shown a positive effect on participants' userelated self-efficacy [ ] . to sum up, empirical evidence suggests that self-efficacy beliefs are malleable and can be effectively enhanced using internet-based interventions [ ] [ ][ ] [ ] .the aim of this study will be to evaluate the efficacy of a newly developed self-help internet-based intervention, new in town, in enhancing social self-efficacy when internet-based interventions by encompassing theory-driven content. we expect that an experimental intervention group will be superior to the control group regarding primary outcome-social self-efficacy-and secondary outcomes such as loneliness, perceived social support, and satisfaction with life. furthermore, we will evaluate the user experience of the intervention. the study is a two-arm randomized controlled trial in parallel design. participants will be randomized into two groups: a self-help internet-based intervention (new in town) and a waiting list control group. the trial was registered at clinicaltrials.gov (identifier: nct ) on st september . the study protocol and informed consent have been approved on th january by the ethics committee of the faculty of psychology at the swps university of social sciences and humanities in warsaw, poland (ref. no. / ). the new in town is an internet-based intervention created by the researchers at the swps university of social sciences and humanities in warsaw. it is available in the polish language version. the mode of internet recruitment and data collection enables potential participants from all over poland to apply for trial enrollment. months. targeted sample is prone to adjustment disorders development. in line with dsm-v, adjustment disorder became chronic when the symptoms persist more than six months from the moment when the trigger has occurred [ ] . as the new in town intervention is focused on soft skills development related to social self-efficacy it cannot be treated as professional help for those individuals who faced clinical symptoms of chronic adjustment disorder. therefore, we have chosen the criterion of months. when explaining participants this criterion we use internal migration definition of statistics poland-"change of place of residence (…) in the territory of poland, related to crossing the administrative border of a gmina (polish administrative unit), including-in case of urban-rural gminas-changes of the place of residence within a gmina, i.e. from rural to urban areas and vice versa" [ ] . the exclusion criterion is the lack of internet access. applicants who meet inclusion criteria will be automatically directed to electronic informed consent to enroll in the study. all study j o u r n a l p r e -p r o o f participants will be informed of their right to delist from the study without any consequences. after giving consent, participants will be asked to complete baseline questionnaires. the intervention aims at increasing social self-efficacy and consists of cognitive behavioral therapy (cbt)-based exercises related to sources of self-efficacy beliefs: ) mastery experiences, ) vicarious experiences, ) verbal persuasions, and ) emotional and physiological states [ ] . intervention contains modules (see table ). users complete increasingly challenging tasks that encourage them to interact with their environment. psychoeducation on social support (e.g. buddy support exercise). psychoeducation on emotional and physiological states as a source of self-efficacy beliefs (e.g. self-care exercise). planning initiating and maintaining interpersonal relationships (e.g. goal setting exercise). all data including informed consent will be stored in cloud-based software, surveymonkey. this platform uses an encrypted connection, which guarantees the security of data transmission. assessments will not require any personal data, except an email address. it is necessary in order to send an online questionnaire link at post-test and follow-up. only authorized persons will have access to the stored data. the sample size will be determined a priori using g*power [ ] . empirical evidence suggests a medium effect of internet-based interventions aimed at increasing self-efficacy beliefs [ ] . in our analysis we will include four outcomes. therefore, we will apply bonferroni's adjustment that will compensate for multiple comparisons and lower the probability level. [ ] . therefore, we plan to include participants at baseline ( participants per condition). after completion of the informed consent and baseline questionnaires, all participants will be randomized and assigned with a : ratio to one of two groups. information about group allocation will be provided within days to participants. blinding allocation is not possible due to the study design. participants assigned to the new in town group will be provided with login details as soon as possible. the waiting-list group will be given login instruction weeks after baseline. both groups receive access to the intervention for a period of weeks. in order to log in to the intervention website, all participants will get a unique password. after logging for the first time each participant is automatically asked to create own password. the participants can change the password to an account any time they wish. the post-test assessment is scheduled at weeks after baseline, follow-up assessment at weeks after baseline. all assessments (baseline, post-test, and follow-up) are self-reports and will be conducted online. research has confirmed the reliability and validity of the internet administration format of self-report psychological questionnaires [ ] . participants will be informed via email to complete assessments and will receive links to online questionnaires. two email reminders will be sent if the questionnaires stay incomplete for one week. eligible participants will be randomized by an independent researcher after the baseline measurement to either an experimental group or a waitlist control group ( : allocation ratio) using an online randomization program (www.randomizer.org). to ensure an equal number of participants in both study conditions we will use non-stratified block randomization with two participants per block. all outcomes will be measured in each assessment; baseline, post-test ( weeks after baseline), and follow-up ( weeks after baseline). exceptions are demographic data and user experience. demographic data will be collected at baseline, while user experience will only be assessed at the post-test among participants allocated to the experimental group. in a feasibility study, the reliability of measures was acceptable, with cronbach's alpha ranging from . to . . the average completion time of online questionnaires was minutes. general self-efficacy scale. social self-efficacy is the primary outcome studied. it will be measured with the general self-efficacy scale (gses) [ ] . the gses consists of two subscales for measuring ) generalized beliefs about self-efficacy ( test items) and ) beliefs about self-efficacy in establishing and maintaining relationships with others ( test items). the remaining test items ( ) are buffer theorems. the respondents give answers on a scale -point likert scale ( = strongly disagree, = strongly agree). in the trial, we will use one subscale, which measures beliefs about self-efficacy in establishing and maintaining relationships with others. social self-efficacy will be indicated by the total sum of items scores, e.g. "i have acquired my friends through my personal abilities at making friends". j o u r n a l p r e -p r o o f higher scores reflect a higher level of self-efficacy. the scale demonstrates good psychometric properties [ ] . de jong gierveld loneliness scale [ ] will be used to measure loneliness. the scale is composed of items; of them are formulated negatively and positively. each item is measured using on -point likert scale ( = definitely yes, = definitely no), e.g. "i often feel rejected". positive items should be reversed. the sum of scores is counted on separate subscales: emotional and social loneliness. the scale can be applied in different data collection modes; in face-to-face interviews as well as in online questionnaires. it is a wellvalidated measure with a bifactor structure [ ] . the berlin social support scale (bsss) [ ] will be used to assess social support. the bsss consists of subscales: perceived available support, need for support, support seeking, actually received support (recipient), provided support (provider), protective buffering scale. the scale contains items that are scored on a -point scale ( = strongly disagree, = strongly agree). before scoring items, negative ones need to be reversed, e.g. "i get along best without any outside help". scores can be counted either on a general scale or subscales. the measure was validated in several studies and showed good reliability [ ] [ ] . in the trial, only of subscales will be applied: perceived available support ( test items), need for support ( test items), and support seeking ( test items). internal consistency and test-retest reliability are highly satisfactory [ ] . swls is widely used to measure satisfaction understood as a component of well-being [ ] . demographic data questionnaire. this short questionnaire contains questions about gender, age, education, profession, tenure, the old and the new place of residence (rural area, city up to , residents, city up to , residents, city up to , residents, city with more than , residents) questionnaire. an overall impression of the intervention will be assessed by the user experience questionnaire (ueq) [ ] . it is a self-reported measure that contains subscales: attractiveness, perspicuity, efficiency, dependability, stimulation, novelty. participants respond to items (e.g. annoying/enjoyable) using a -point scale (- = the most negative answer, = neutral, + = the most positive answer). the ueq presents high internal consistency and good validity of scales [ ] . generalized estimating equations (gee) approach will be used to examine changes in primary and secondary outcomes over time and to assess differences between experimental and waitlist control group. this approach allows the correlated structure of data from repeated measures. what is more, gee is nonparametric and does not assume that the dependent variable is normally distributed [ ] [ ] [ ] . we will include group (experimental/waitlist control), measurement time and interaction between group and time as independent variables. dependent variables will include social self-efficacy, loneliness, perceived social support, and satisfaction with life. qic coefficients will be used to choose the best assumption for the working correlation matrix. we will follow intention-to-treat j o u r n a l p r e -p r o o f (itt) principles and use model-based imputation to handle missing values [ ] . adverse events will be assessed through the categorization of primary outcome change. we will recognize change that: ) is higher than - % from baseline as deterioration events, ) is between - % to % from baseline as non-response events, ) is between - % from baseline as minimal response events, and ) is higher than % from baseline as remission events. this classification scheme will enable us to compare outcomes, such as worsening with improving symptoms or non-response to intervention [ ] [ ]. to assess possible measurement bias we will compare the outcome change with and without the effect of missing data. all analyses will use intention-to-treat (itt) principles. we will additionally perform per-protocol analyses to examine the robustness of the effects. individual characteristics of participants can become confounding variables. random assignment to groups minimizes the potential for confounding. nevertheless, to assess possible assignment bias we will compare demographic and baseline characteristics between experimental and waitlist control group. the choice of sensitivity analyses will be, therefore, to some extent, data-driven [ ] . migrants go through a stressful process of transition and adaptation which may be related to problems in the area of well-being and mental health [ ] . however, research suggests that adaptation of migrants may be facilitated by social self-efficacy beliefs [ evidence also suggests that self-efficacy is malleable and can be effectively reinforced using internet-based interventions [ ] [ ][ ] [ ] . because the number of migrants is steadily increasing over the past years [ ] and more than % of polish citizens are internal migrants [ ] , the current challenge is to develop an effective and easily accessible intervention targeting this population. with our study, we hope to gain insight into the efficacy and acceptance of the new in town-self-help internet-based intervention aimed at increasing j o u r n a l p r e -p r o o f social self-efficacy among internal migrants in poland. the study is a randomized controlled trial with a waitlist control group. the primary outcome is social self-efficacy. secondary outcomes include loneliness, satisfaction with life and perceived social support. we will also explore user experiences. the study is not free from limitations. firstly, the online platform does not collect the data of the way participants will use the intervention (duration and frequency of being logged in to it). it is crucial to explore participants' patterns of accomplishing modules and identify the most crucial modules. each intervention module is activated one by one, but participants have always the possibility to return to previous ones. dates of module activation are not set in advance. therefore, the chance that some participants might complete the whole intervention at once still exists. on the other hand, open access to non-blocked modules allows participants to use the intervention at own pace and to adapt exercise completion to the daily life duties. at the post-test, we plan to collect user experience data that might be helpful in enhancing the intervention. secondly, the new in town and assessments were not provided on the same platform. this inconvenience may have an impact on drop-out rates. relatively high dropout rates are found in a number of internet-based interventions studies [ ] [ ] . therefore, we plan to adjust for missing data using the gee approach [ ] . the other concern is recruitment. participants will be recruited via social and traditional media campaigns. it will be a self-selected sample that might be highly motivated for internet-based interventions. this fact could affect the outcomes and become the main concern that should not be ignored without considering further research directions. for this reason, we plan in the near future to transfer the intervention to a more traditional medium and conduct it in the form of workshops or e-learning courses dedicated to freshman college students and assess its efficacy as well. moreover, the control group in our study is a waitlist control. research has shown that using this type of control condition may lead to bigger j o u r n a l p r e -p r o o f treatment effect sizes estimates compared to no treatment and psychological placebo [ ] . however, the aforementioned research was on cbt for depression and therefore generalizability of this evidence may be limited. additionally, one of the inclusion criteria is having changed the place of residence in the last months. therefore, participants in a waitlist control group can wait longer to access the intervention than they were between changing the place of residence and study enrolment. because of that study could yield more conservative results. future studies should focus on comparing the new in town with a different intervention as an active control condition. there will also be several strengths of this study. firstly, the content of the new in town intervention is theory-driven. exercises in the intervention are based on the principles of cognitive behavioral therapy and relate to four sources of self-efficacy beliefs. according to social cognitive theory, these beliefs can be enhanced by interpreting information from mastery experiences, vicarious experiences, verbal persuasions, and emotional and physiological states [ ] . secondly, we will use well-validated measures of primary and secondary outcomes. the strong aspect of the study design is also using two follow-up measurement points that enable us to track long-term effects. finally, the new in town is designed specifically for migrants, who are potentially at greater risk of difficulties in the social area [ ] [ ] . mind the gap!" integrating approaches to internal and international migration overcoming barriers: human mobility and development common mental health problems in immigrants and refugees: general approach in primary care psychological adaptation of chinese sojourners in canada jin li xm. depression and associated factors in internal migrant workers in china the effects of social connections on self-rated physical and mental health among internal migrant and local adolescents in self-efficacy in stressful life transitions self-efficacy: the exercise of control self-efficacy as a mediator between stressful life events and depressive symptoms differences based on history of prior depression the relationship between cross-cultural adjustment and the personality variables of self-efficacy and self-monitorin work adjustment and job satisfaction of filipino immigrant employees in canada learning to fit in : an exploratory study of general perceived self efficacy in learning to fit in : an exploratory study of general perceived self efficacy in selected refugee groups returning refugees : psychosocial problems and mediators of mental health among malawian returnees belonging and connection to school in resettlement : young refugees , school belonging , and psychosocial adjustment self-efficacy, perceived social support, and psychological adjustment in international undergraduate students in a public higher education institution in malaysia negative affect in east german migrants: longitudinal effects of unemployment and social support the selfefficacy scale: construction and validation guide for constructing self-efficacy scales self-efficacy specificity and burnout among information technology workers: an extension of the job demand-control model sources of social self-efficacy expectations : their measurement and relation to career development adult attachment , social self-efficacy , self-disclosure , loneliness , and subsequent depression for freshman college students : a longitudinal study acculturative stress, and depression in african, asian, and latin american international college students.pdf measuring social self-efficacy in a culturally diverse student population c the psychological adaptation of international and migrant students in canada the psychological adaptation of overseas and migrant students in australia migration, social mobility and common mental disorders: critical review of the literature and meta-analysis. ethn health migration and mental health self-efficacy: a theoretical analysis of its determinants and malleability sources of self-efficacy in school: critical review of the literature and future directions effects of internet-based self-efficacy intervention on secondary traumatic stress and secondary posttraumatic growth among health and human services professionals exposed to indirect trauma efficacy of an internet-based problem-solving training for teachers: results of a randomized controlled trial flourishing students: a longitudinal study on positive emotions, personal resources, and study engagement web-based nutrition education intervention improves self-efficacy and self-regulation related to increased dairy intake in college students a controlled trial of an internet-based intervention the national census of population and housing . . . who. who announces covid- outbreak a pandemic american psychiatric association. diagnostic and statistical manual of mental disorders. american psychiatric association terms used in official statistics power : a flexible statistical power analysis program for the social, behavioral, and biomedical sciences self-guided psychological treatment for depressive symptoms: a meta-analysis public library of science computers in human behavior internet administration of self-report measures commonly used in research on social anxiety disorder : a psychometric evaluation manual of the loneliness scale validating the polish adaptation of the -item de jong gierveld loneliness scale soziale unterstützung bei der krankheitsbewältigung: die berliner social support skalen (bsss) long-term effects of spousal support on coping with cancer after surgery the satisfaction with life scale is the shift in chronotype associated with an alteration in well-being ? the satisfaction with life scale and the emerging construct of life satisfaction further validation of the satisfaction with life scale: evidence for the cross-method convergence of well-being measures construction and evaluation of a user experience questionnaire longitudinal data analysis using generalized linear models to gee or not to gee: comparing population average and mixed models for estimating the associations between neighborhood risk factors and health an overview of longitudinal data analysis methods for neurological research dealing with missing outcome data in randomized trials and observational studies measurement of symptom change following web-based psychotherapy: statistical characteristics and analytical methods for measuring and interpreting change a comparison of the characteristics and treatment outcomes of migrant and australian-born users of a national digital mental health service a tutorial on sensitivity analyses in clinical trials: the what, why, when and how adherence in internet interventions for anxiety and depression dropout from internet-based treatment for psychological disorders waiting list may be a nocebo condition in psychotherapy trials: a contribution from network we thank aleksandra bis for contributing to the pilot study. key: cord- -dbtc bo authors: runkle, jennifer d.; sugg, margaret m.; leeper, ronald d.; rao, yuhan; mathews, jessica l.; rennie, jared j. title: short-term effects of weather parameters on covid- morbidity in select us cities date: - - journal: sci total environ doi: . /j.scitotenv. . sha: doc_id: cord_uid: dbtc bo abstract little is known about the environmental conditions that drive the spatiotemporal patterns of sars-cov- , and preliminary research suggests an association with weather parameters. however, the relationship with temperature and humidity is not yet apparent for covid- cases in us cities first impacted. the objective of this study is to evaluate the association between covid- cases and weather parameters in select us cities. a case-crossover design with a distributed lag nonlinear model was used to evaluate the contribution of ambient temperature and specific humidity on covid- cases in select us cities. the case-crossover examines each covid case as its own control at different time periods (before and after transmission occurred). we modeled the effect of temperature and humidity on covid- transmission using a lag period of days. a subset of cities were evaluated for the relationship with weather parameters and cities were evaluated in detail. short-term exposure to humidity was positively associated with covid- transmission in cities. the associations were small with ¾ cities exhibiting higher covid transmission with specific humidity that ranged from to g/kg. our results suggest that weather should be considered in infectious disease modeling efforts and future work is needed over a longer time period and across different locations to clearly establish the weather-covid relationship. experimental and observational studies demonstrate the influence of meteorological parameters on the seasonal transmission of influenza, human coronavirus (hcov), and human respiratory syncytial virus (rsv), which are often characterized by distinct increases in incident cases and detection frequency in the winter months (lowen and j o u r n a l p r e -p r o o f in the us. as the us begins its public health response to covid- , the implementation of extensive public health interventions are needed at appropriate time scales to mitigate the public health and economic impacts of the covid- pandemic. research on the seasonality and influence of meteorological parameters on covid- , such as temperature and specific humidity, can be used to inform the timing of effective interventions to mitigate sars-cov- /covid- transmission at the local scale to save countless lives and resources. the objective of this research is to examine the association between meteorological variables and covid- in us cities. unlike previous studies, we will use a highresolution spatiotemporal meteorological dataset to answer the following: is there an association with meteorological parameters and covid- ? if so, which meteorological parameters predict covid transmission? is the association stronger after accounting for locally implemented social distancing measures? how does this relationship vary spatially across the us? by answering these questions, the knowledge gained on the contribution of environmental factors like temperature and humidity on transmission can be paired with other nonpharmaceutical interventions related to behavioral (e.g., wearing face mask, washing hands) factors that boost immunity or the timing of social distancing measures with seasonal spikes in influential environmental parameters to reduce transmission. this retrospective case-crossover study examined the nonlinear and delayed association between environmental factors and covid- j o u r n a l p r e -p r o o f transmission. we selected the following us locations that exhibited high relative caseloads of covid- in the early stages of the pandemic for their underlying populations: seattle, washington; new york, ny; albany ga; new orleans, la.; bridgeport-stamford-norwalk, conn.; pittsfield, mass; detroit, mi; chicago, il. figure is a map of the study locations. we assumed at least a median incubation period of . days (lauer et al ) . case counts were log-transformed, and time series were created when cities had more than new daily cases. because deidentified and anonymized data on case morbidity were obtained from a publicly accessible data portal this research did not involve participant consent and institutional review was not warranted. environmental parameters. meteorological data were derived from the european center for median range weather forecast (ecmwf) atmospheric reanalysis dataset (era- ) (c s, ). era- provides a suite of hourly weather parameters that may affect local covid- transmissions at a -km spatial resolution. while not commonly used in environmental health studies, the advantage that era- data provides over individual weather station data is that spatial heterogeneity is more representative and the estimation of health effects of temperature and humidity can be derived in locations far j o u r n a l p r e -p r o o f from weather stations or without any station. previous research has shown that reanalysis data and weather station data show similar health risk estimates (roye et al ). daily average near-surface air temperature, specific humidity, and solar radiation were extracted from era- for each study location by a simple spatial average. because relative humidity (rh) is highly correlated with temperature, we chose to instead include specific humidity as a predictor variable in the analysis. heat mapping. preliminary studies have suggested that the combination of humidity and air temperature could affect the transmission of local covid- cases (e.g., sajadi et al., , lou et al., , oliveriros et al., . we examined the association between local covid- cases and air temperature and specific humidity using the density heatmap. to construct the density heatmap, the daily confirmed covid- case reports were first separated based on their corresponding daily mean air temperature (every °c) and mean specific humidity (every . g/kg). all daily confirmed case counts were classified into the same air temperature and specific humidity conditions (e.g., °c < t air < °c and g/kg < q < . g/kg) and evaluated together as a density measurement. this explanatory analysis was intended to demonstrate the association of covid- cases with the combined effect of air temperature and specific humidity. the heatmap could identify the range of optimal meteorological conditions for local transmissions. considering the incubation period of covid- , we applied the analysis j o u r n a l p r e -p r o o f nonlinear model (dlnm). this approach is more flexible than conditional logistic regression (armstrong et al ) in that it allows for overdispersion. the application of the dlnm to the case-crossover design provides a means to assess the nonlinear and delayed effects, as well as the cumulative exposure-response between short-term daily average exposure to meteorological parameters and daily counts for covid- cases. we performed separate analyses for our primary health outcome --covid- morbidity --and each meteorological parameter relative to the median and quartiles (i.e., th versus th). this approach is suitable for studying the effects of time-varying exposures (e.g., intermittent changes in meteorological) on a rare, acute condition (i.e., covid- transmission) (armstrong et al., , malig et al., , guo et al., . we relied on the following equation: where t is the day of the observation; y t is the observed daily case counts on day t; α is the intercept; t t,l is a matrix obtained by applying the dlnm to temperature or humidity, β is a vector of coefficients for t t,l , and l is the lag days. strata t is a categorical variable of day ( day time period) used to control for trends, and λ is a vector of coefficients. sd t is a binary variable that is " " if day t was a social distancing order, and υ is the coefficient. our model was adapted from similar work by guo et al who also employed a case-crossover design and dlnm to investigate the effects of temperature on mortality (guo et al ). given that the incubation period between exposure and symptom occurrence is to days (linton et al ), we used a maximum -day lag period to explore the potential delayed association of temperature and humidity in our model for approximating the pre-and post-infection period for each case. sensitivity analysis. a sensitivity analysis was conducted to select degrees of freedom for the lag polynomial ( - degrees of freedom) and the response polynomial ( - degrees of freedom) for new orleans, la (data not shown). in addition, we changed the maximum lag to and days, which gave similar results (data not shown). prior research has examined a day, day to day lags for covid- transmission (ma et al all the way to a lag period extending to days for meteorological parameters (islam et al ). for our initial examination of meteorological parameters independently, we compared the best model fit using quasi-akaike information criterion (q-aic) to determine the optimal degrees of freedom and lag periods. q-aic is a well-established technique for sensitivity analysis and was used to compare dlnm-only models and dlnm+case-crossover models to confirm the final model selection (guo et al. ) . models were also examined for the adjustment for trends, such as the day of the week. however, due to the short time series, differences were minimal or resulted in a poor fit (high q-aic) and thus we selected the most j o u r n a l p r e -p r o o f parsimonious model. the "dlnm" package was used to create the dlnm model (gasparrini ) using r statistical software (r core team ). we adopted the rare-disease assumption where our study hypothesis tested the association between weather exposure and a disease (i.e., covid- ) characterized by low prevalence. therefore, we assumed the odds ratio to approximate the relative risk. all relative risks (rr) were presented with corresponding % confidence intervals ( % cis). attributable burden of covid- transmission due to weather. in epidemiology, measures of potential impact are used to examine the expected impact of changing the distribution of one or more risk factors in a particular population (kleinbaum et al , szklo et al . for example, the attributable risk, also known as the etiologic fraction, is used to examine the proportion of all new cases in a given time frame that is attributable (or causally associated) to the exposure of interests (szklo et al ) . because the evidence-base linking covid- transmission and weather is new and evolving, it is too early to assume a causal association. therefore, we relied on the excess fraction (ef) as an analogous, but alternative measure to the attributable risks in our analysis, to approximate the excess caseload due to exposure. to examine the attributable burden of transmission for covid- due to weather we calculated the percent excess fraction for humidity and temperature for individual cities. we used the following equation: % ef = b x (rr i - ) / b x (rr - . i ) + . ), where b is the point prevalence of covid- for each city. point prevalence was calculated as the number of cases over the study period divided by the total population in a specific city. we table ). the crude rate of covid- per location was highest for new orleans, la ( daily cases per , people), followed by new york city, ny ( daily cases per , people), albany, ga ( daily cases per , people), and bridgeport, ct ( daily cases per , people). the lowest rates of covid- cases were in seattle, wa ( daily cases per , people), and pittsfield, ma ( cases per , people). the highest crude death rates were observed in new york city, ny ( daily deaths per , people), albany ga ( daily deaths per , people), new orleans, la ( daily deaths per , people) and detroit, mi ( daily deaths per , people). the density heatmap ( figure ) presents a descriptive explanatory analysis of the combined association of temperature and specific humidity on covid- cases for the selected cities. based on the heatmap, covid- cases were more common in low specific humidity ( - g/kg) and low temperature ( - °c) conditions. this association was consistent when we consider different incubation times (lag - days). all locations. table shows the goodness of fit (qaic) values across model types for all locations and parameters, which is a common validation and sensitivity technique (e.g, gasparrini et al. , guo et al. . in general, the humidity was the strongest j o u r n a l p r e -p r o o f predictor for covid- cases, with a better model performance for humidity than temperature across all model types and study locations. case crossover models performed higher in seattle, wa, new york city, ny, chicago, il, and new orleans, la. the variation in the dose-response profile for humidity was negligible before and after adding temperature as a predictor into the model, indicating that humidity exhibited a robust association. model performance was poor (indicated by high qaic values) for detroit, mi, pittsfield, ma, and bridgeport, ct. results for these cities were insignificant and therefore not reported in the final results (supplemental figures , ) . overall, the case-crossover + dlnm model outperformed the dlnm only model. however, select locations had better model fit for dlnm only (e.g., albany, ga), although marginally better. results were presented for the following cities: new orleans, la, albany, ga, and seattle, wa, and models were selected based on qaic values. dlnm and casecrossover models were also constructed for these locations to analyze the effect of solar radiation (watts/m ) on covid incidence rates. new orleans, la. the relative risk for covid- exhibited a u-shaped relationship with increases in cases at high and low humidity in new orleans. with reference to the median humidity, relative risk peaked at minimum ( g/kg, rr: . , ci: . - . ) and maximum ( g/kg, rr: . , ci: . - . ) values. similarly, temperature exhibited a u-shaped relationship with reference to the median and a significant relative risk at - °c (rr: . - . ; ci: . - . ) and at the maximum observed temperatures ( °c; rr: . , ci: . - . ). solar values exhibited an inverted u-shaped relationship with a higher relative risk from - (watts/m ) (figure ). albany, ga. temperature and solar radiation were not significant predictors of covid- cases. with reference to the median humidity, significant relative risk is observed from to g/kg (rr: . - . , ci: . - . ). due to a lower qaic value and more robust results, unlike other cities, a dlnm-only model was applied to the humidity and the covid- relationship for albany, ga (figure ) . incidence that revealed a protective effect from to °c (rr: . - . , ci: . - . ), whereas no relationship was observed between humidity and solar radiation and covid- cases in nyc ( figure ) . seattle, wa. the temperature was significant from to °c (rr: . - . , ci: . - . ). however, the humidity was significant at the lowest values with an increased risk of transmission occurring at less than g/kg (rr: . , ci: . - . ). lower risk of transmission was observed for the lowest values of solar radiation (i.e., less than watts/m , rr: . , ci: . - . ) (figure ) . the excess burden of new covid- cases due to weather. overall, the attributable burden of excess covid- cases associated with exposure to humidity and temperature was low for each city (table ). the excess fraction was the highest for j o u r n a l p r e -p r o o f new orleans, with . to . % of new cases occurring within the humidity range of g/kg to g/kg and . to . % occurring within the temperature range of (°c) to (°c). in this study, we examined whether daily meteorological patterns in humidity, temperature, and solar radiation were associated with the transmission of covid- in u.s. cities that emerged as early hot spots for infection. we applied the dlnm to a case-crossover design to assess the nonlinear and delayed effects of meteorological parameters on covid- incident cases. to our knowledge, this study is the first to assess the effects of meteorological variables on covid- morbidity using a robust distributed lag nonlinear model and case-crossover design. we observed a weak but statistically significant relationship between covid and meteorological parameters for (sajadi et al., ) . humidity was observed as the best predictor for the coronavirus outbreak followed by temperature and solar radiation. the majority of cities included in this study demonstrated a nonlinear dose-response relationship between a range of specific humidity conditions and sustained covid- transmission. more specifically, of the cities were characterized by a significant relationship between covid- transmission and humidity (e.g., albany, ga, new orleans, la, and chicago, il). humidity in the range of to g/kg (analogous to an absolute humidity range of . - . g/m ) was a significant predictor of covid- cases and resulted in an up to two-fold increased temperature and solar radiation did not exhibit a strong association with covid incidence in our study locations. our results for new york city, ny support and extend previous research on covid and meteorological parameters in new york city that found a significant association with temperature using simple correlation coefficients (bashir ). bashir et al. observed a direct association with higher temperatures predicting higher covid- cases ( ). conversely, our research found a protective effect at higher temperatures and is corroborated by earlier studies (qi et al., , unlike previous studies examining the influence of meteorological factors on covid transmission, one strength of our study is the adjustment for social distancing measures (sajadi et al ) . most environmental health research includes either a variable for relative humidity (rh) and/or absolute humidity (ah). specific humidity is more conservative and less susceptible to changes in pressure and temperature compared to ah. further, in addition to the confounding influence of humidity and temperature, rh is typically not useful as a stand-alone humidity variable in environmental health or epidemiological research. our results are only comparable to a few recent studies examining the association between covid- and specific humidity (e.g., ma et al., , sajadi et al., . recent research has demonstrated the linkage between poor air quality and covid- mortality (wu et al. ) , and in our study, we did not adjust for background air quality measures as a potential confounding factor. while our modeling strategy did adjust for social distancing measures, our estimates do not account for underreporting of case counts (lachmann ) , demographic data on cases, changes in testing capacity, or the date of onset of covid symptoms. this study did not include information on the newly discovered coronavirus as the primary cause of severe acute respiratory syndrome correcting under-reported covid- case numbers. medrxiv the frequency and seasonality of influenza and other respiratory viruses in t tennessee: two influenza seasons of surveillance data the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application yangy, et alincubation period and other epidemiological characteristics of novel coronavirus infections with right truncation: a statistical analysis of publicly available case data defining the epidemiology of covid- -studies needed roles of humidity and temperature in shaping influenza seasonality the role of absolute humidity on transmission rates of the covid- outbreak effects of temperature variation and humidity on the death of covid- in wuhan a time-stratified case-crossover study of ambient ozone exposure and emergency department visits for specific respiratory diagnoses in california determining the seasonality of respiratory syncytial virus in the united states: the impact of increased molecular testing seasonal variations of respiratory viruses and etiology of human rhinovirus infection in children seasonality of respiratory viral infections. annual review of virology coronavirus infections-more than just the common cold coronavirus as a possible cause of severe acute respiratory syndrome covid- transmission in mainland china is associated with temperature and humidity: a timeseries analysis. science of the total environment, . r core team ( ). r: a language and environment for statistical computing. r foundation for statistical computing temperature and latitude analysis to predict potential spread and seasonality for covid- the impact of temperature and absolute humidity on the coronavirus disease (covid- ) outbreak-evidence from china potential factors influencing repeated sars outbreaks in china epidemiology: beyond the basics global influenza seasonality: reconciling patterns across temperate and tropical regions environmental predictors of seasonal influenza epidemics across temperate and tropical climates high temperature and high humidity reduce the transmission of covid- exposure to air pollution and covid- mortality in the united states the relationship between air quality and respiratory pathogens among children in suzhou city key: cord- -o gfukzg authors: unruh, mark aaron; yun, hyunkyung; zhang, yongkang; braun, robert t.; jung, hye-young title: nursing home characteristics associated with covid- deaths in connecticut, new jersey, and new york date: - - journal: j am med dir assoc doi: . /j.jamda. . . sha: doc_id: cord_uid: o gfukzg nan nursing home patients have been disproportionately affected by covid- . it has been reported that one-fourth of all covid- deaths nationwide occurred in nursing homes and other long-term care facilities. the objective of this study was to compare the characteristics of nursing homes with covid- deaths to other nursing homes using data from connecticut, new jersey, and new york. we merged data on nursing home characteristics from the ltcfocus database (long term care: facts on care in the us) with data on nursing homes with covid- deaths provided by the states of connecticut , new jersey, and new york. data from connecticut included deaths as of april th, new jersey as of april th, and new york as of april th. after excluding facilities with incomplete information, our sample included , nursing homes. data from connecticut and new jersey identified nursing homes with or more covid- deaths, but data for new york only identified nursing homes with or more covid- deaths. therefore, we created a binary outcome of whether a nursing home had or more covid- deaths. nursing home characteristics included mean age of residents, percent female, percent white, mean resource utilization group case-mix index, mean activities of daily living (adl) score, percent restrained, total number of beds, occupancy rate, for-profit status, multi-facility chain membership, mean direct care hours per patient day, presence of an the distributions of the percent of patients covered by medicaid patients and the percent covered by medicare were also included. predicted probabilities were estimated with logistic regression using the covariates listed above in addition to indicators for states. secondary analyses were conducted ( ) with samples for each of the three states and ( ) by repeating our primary analysis with the sample limited to nursing homes with or more beds. although an outcome measure reflecting the number of covid- deaths per nursing home bed would have been ideal, the data did not permit this. nevertheless, our regression estimates reflect the probability of a nursing home having or more covid- deaths, holding the number of beds in the facility constant. among the , nursing homes in our sample, ( . %) had or more covid- deaths. estimates from our primary analysis (table) estimates for these measures were not statistically significant for nursing homes in connecticut or new jersey. the results of our secondary analysis of nursing homes with or more beds (table) were largely consistent with our primary analysis with one key exception; more direct care hours per patient day were associated with a lower probability of covid- deaths (- fresh data shows heavy coronavirus death toll in nursing driven to tiers: socioeconomic and racial disparities in the quality of nursing home care. the milbank quarterly separate and unequal: racial segregation and disparities in quality across us nursing homes key: cord- -m ig hii authors: sharp, mindy mcgarrah title: if you’re ready, i am ready (but the wait is harming us both) individual risks in institutional conversions date: - - journal: pastoral psychol doi: . /s - - - sha: doc_id: cord_uid: m ig hii rambo, adele, and a religion professor walk into a coffee shop. what in the world do they have in common? this essay integrates lewis rambo’s scholarship on conversion with pop singer adele’s popular song “send my love to your lover” to understand and redress inequity in individual risk within processes of institutional conversion. the author focuses on practices of inclusion in institutions of higher education using the specific example of theological schools with aspirational school mission statements that embrace equity and diversities. she argues that bringing rambo and adele into conversation with anecdotal and published research on institutional (in)justice illuminates four practices that institutions could adopt to better align practice with promise and thereby promote wellness for all who are impacted by institutional health. album for my birthday. we listened to it together in the car while driving to and from school and various activities and commitments. the song entitled "send my love to your new lover" quickly became a favorite in family car sing-alongs, especially its final overlapping chorus. the chorus has two different phrases sung in different melodies at the same time, and we loved each having a part in singing the harmonies. we talked about what the song could mean in contexts beyond a coupled love relationship but generally focused more on joining our voices with the powerful voice of adele. my family is not alone in being drawn to the power of adele's voice and this song in particular. as of the drafting of this paper, the youtube version of the music video for just this song registered over million downloads. for a stretch of time when it was our family's # car song, i found myself humming it between meetings, classes, reading, and writing. not surprisingly, during this time adele's "send my love to your new lover" song would often be an earworm throughout my day. one ordinary workday while waiting on a notoriously slow copy machine, i realized that "my" line "if you're ready, i am ready" was playing in my head. i was struck by hearing the words as descriptive of what's at stake in relationships where partners fail each other, where people get wounded, and where possibilities for transformation could lead to change in future relationships. i thought about this in the context of collective conversion in institutional life in theological education, what can go wrong, and which bodies get more or less wounded in the process. i was pondering the age-old theological and philosophical debate of the difference between is and ought. why is what is happening so different from what ought to be happening? why is there so often such a chasm between is and ought? what kinds of changes or conversions are needed to close the gap? as a theological educator, i have been fascinated by the aspirational mission statements of seminaries and theological schools that stress prophetic witness, truth, and justice. yet, my studies in postcolonialism have exposed histories of educational and religious institutions, methodologies, and curricula as deeply flawed, at times serving as instruments of discrimination and oppression (hooks ; smith ) . i wrestled with these thoughts in front of the copy machine while adele's chorus "if you're ready, i am ready" played in my mind. what does "being ready" mean in the context of theological education? ready for what? i heard adele calling for readiness in her lyrics, including readiness to live into who we say we are in our educational mission statements. adele sings of readiness to learn from relational failures and change one's future practices for the better. what does it mean to do better and learn from relational failures on an institutional level? these kinds of questions became a secondary earworm influencing how i bear witness to, interpret, and participate in some of the more difficult aspects of institutional life. in this paper, i weave three unlikely conversation partners-adele's song "send my love to your new lover," lewis rambo's theory of conversion, and a practical theological engagement with inclusive and equitable institutional practices. while they may seem unrelated, weaving adele, rambo, and institutional practices together yields insights into practices of institutional conversion that could address gaps between the inequities and injustices that exist and the aspirational educational missions that many schools claim. in order to redress ways in which institutions of education, including religious and theological education, are shaped by oppressive and exclusive histories and habits, institutions must embrace and expect change, what rambo calls conversion. one sign of change would be robust diversities represented in curricula, faculties, administration, students, boards, and other stakeholding groups and aspects of teaching and learning. but, change is hard, and institutions, like individuals, can resist or be slow to embrace equity and inclusion in practice (sharp ) . at the copy machine, i thought of friends, once relieved at the promise of an academic job after years of unpaid doctoral studies, who were now leaving tenure-track faculty positions to start over at other schools or leaving the academy altogether. nearly all who came to mind inhabited minoritized identities. the online publication the feminist wire's scathing article "black academic women's health forum" had already been haunting me and helping me recognize institutional dynamics across higher education where friends were and were not struggling in academic vocations (cox et al. ) . the forum editors amplified one anonymous reader's comment on the forum: with every piece i read, i felt like a layer of my skin was being pulled back, like more and more was finally revealed. i've spent so many years on the margins of this institution that i got used to making myself invisible, on purpose. i am seeing myself again. i will demand to be seen. thank you. (cox et al. ) most folks i knew and read about who were suffering serious health consequences related to institutional stress were underrepresented in various ways due to race, gender, sexuality, nationality, religious identity, and more, and had been hired with great joy by institutions who celebrated their initial inclusion. yet, the relationship with their institutional contexts had not lived up to the promises of inclusive institutional practices. stress was increasingly manifest in more minoritized bodies while other dominant-culture colleagues appeared to be just fine. for some community members, the way things had always been seemed to be working-or folks long ago had adapted to a normalized system and become more change averse. other community members seemed to be holding on by a thread. in my particular field of study, there was growing recognition among pastoral theologians of the spiritual and material costs of institutional demands in theological education-the "maceration" of faculty members-often if not always borne disproportionally (miller-mclemore ) . the feminist wire forum editors aimee meredith cox, aishah shahidah simmons, and tamura a. lomax summarized the strong resonance of readers with the online forum mentioned above with the declaration: "we exhaled into each 'peace' and they breathed back into us. we let the world know loud and clear: we want to be well! we will be well!!" (cox et al. ) , echoing novelist and activist toni cade bambara's haunting question in her novel the salt eaters: "are you sure, sweetheart, that you want to be well?. .. just so's you're sure, sweetheart, and ready to be healed, cause wholeness is no trifling matter. a lot of weight when you're well" (bambara (bambara / . just what does an institution of theological education that supports wellness equitably look like? and who decides? colleagues who came to my mind in front of the copy machine had experienced much heartbreak and many conflicting narratives swirling in and beyond various communities, but this was not the last word. when the institution is slow to change, individuals can make declarations of collective wellness in public profession. in interviews, adele also declared wellness on her own terms, reporting that , her third album, was the making-up album after the heartbreak album and her breakout record , each named for her age at the time of recording the album (epworth and adkins ; adele n.d.) . the song "send my love to your new lover" is, like many adele songs, set in a strong and confident voice, pointing to a coherent sense of self that is able to recover and reflect on relational dynamics gone wrong-or certainly hopes or pretends to do so while still carrying wounds of letting go of what once was. adele's song "send my love to your new lover" is described by the singer herself as communicating that she "can finally reach out a hand to my ex. let him know i'm over it" (lamont ) . while resolved, "send my love to your new lover" is not static but rather emotionally complex, evoking layers of movement (bacle ) . truth-telling regarding both past heartbreak and future resolve, the lyrics charge a former lover to do better with their next relationship, to break a cycle of harm, to change. the song's narrator describes the release that comes with letting go and freeing oneself from a toxic relationship that doesn't support well-being. i hear adele's lyrics not only in contexts of interpersonal relationships but also as descriptive of the general experience of individuals caught up in systems not structured to support their wellness who have to choose between either staying or protecting their wellbeing, especially when institutions fail to deliver on promises of change. adele's "send my love to your new lover" can be read as an anthem for unmasking individual risk in institutional conversion. the song's lyrics can help clarify dynamics involved in institutional deep change. moving from systemic harm toward institutional wellness is a kind of conversion process, leading me to interrogate adele's powerful sung call for change with scholarship on conversion. lewis rambo's classic book-length treatment of conversion, understanding religious conversion ( ), provides language for making sense of discernable aspects within the sometimes ambiguous and usually unending life-long process of conversion. bringing adele and rambo together, i argue, offers particular insights for understanding and living in the midst of institutional change. in the following sections, i will describe four elements of institutional conversion that flow from the conversation between lewis rambo's decades of research on religious conversion and what i was hearing as a pointed call for change in adele's "send my love to your new lover." i locate these insights in the realm of theological education, where i work, but imagine they could help illustrate similar dynamics in other areas of higher education and institutional life. life is full of change and needs for change. the question is, do we want to marshal this change in the service of being well? theological education is in a precarious moment, wrestling with institutional, ecclesial, and cultural changes while being called to conversion to just, equitable, inclusive practices that honor and celebrate multiple diversities. in short, institutions of learning are presently in a decolonizing conversion process that is yet to be fully realized. educational infrastructure built centuries ago to prepare young white men for mainline religious leadership in the united states and missionary service abroad now hosts an ecumenically and internationally diverse faculty, staff, and administration, as well as a diverse student body preparing to serve in a large variety of faith-based and other creative forms of leadership in a world increasingly recognized as globalized and interconnected. tensions between tradition and innovation abound while corporate identity shapeshifts at the level of school, denomination, and beyond. member schools of the association of theological schools, whose mission statements often indicate aspirations of hospitality and inclusion, are being called to conversions through transformations to inclusive, just, and prophetic policies and practices. there is not necessarily agreement on what this means, but it is increasingly clear that much is at stake. practical theology and pastoral psychology are well positioned to help integrate theory and aspirational commitment with practice. connecting popular religiosity with scholarly theology is at the heart of these disciplines that weave theory and practice, learning what works and doesn't work to support individual and collective well-being. connecting adele's "send my love to your new lover" and rambo's study of conversion is illuminating. conversion scholar rambo's theory of discernible elements within conversion processes can help assess where theological schools may be stuck or slowed in their decolonizing conversion process to more just and inclusive institutional practices. for the purposes of this paper, i use marc baer's definition of conversion as "an intensification of belief and practice of one's own religion.. .. [w]here one did not give other than cursory thought or attention to the theology of one's faith or engage in keeping wholeheartedly to its requirements, one devotes one's mind and body fully to understanding and embracing the religion" (as quoted in rambo and farhadian , p. ) . using this overarching definition of conversion as "intensification," i consider rambo's seven stages of conversion experiences in institutional settings, bearing in mind that "spiritual transformation affects work place culture" (paloutzian , p. ; see also sandage et al. ) . within theological education at the institutional level, rambo's first two stages of conversion, contemporary contexts and crises, are clearly present. his next three stages of conversion, what he names quest, encounter, and interaction, present sticking points in a decolonizing conversion to more just practice within theological education. published reports from accrediting bodies, ethnographic studies, and theoretical engagements espouse wide agreement that present structures of theological education are not as just, inclusive, and equitable as they/ we profess and aspire to be (association of theological schools ; muhs et al. ; cox et al. ). further, tenure and retention of diverse faculties hasn't changed much even while faculty hires have diversified (association of theological schools ), it is clear that seminaries that want to practice more equity, inclusion, and diversity are not necessarily sustaining these aspirations over time at the level of faculty, whose responsibility includes embodying institutional mission through curricula. like many stage theories, commitment and consequences, what rambo names as the final two stages of conversion, come after addressing stuck places in earlier phases. a quick review of the mission statements of the seventeen institutions represented at the new directions in pastoral theology meeting where i originally presented this paper suggest aspirational missions of transformative education; well beyond this sample, association of theological schools member schools report "diversity" as one of the top six priorities for theological schools (gin , p. ) . what does it look like in practice to strategically prioritize diversities? what kinds of institutional change or conversion are required? while reviewing rambo's seven stages of conversion, it becomes clear that adele's "send my love to your new lover" is one resource that can help put language to what is at stake in remaining stuck in the middle of a conversion process at an institutional level. who bears more and who bears less individual risk of woundedness and wellness? to be sure, more minoritized scholars are often scapegoated along the way when theological schools that profess readiness to inhabit more just practices that are hospitable to greater diversities find themselves/ourselves stuck or prematurely professing achievement regarding the fullness of conversion. in conversation with rambo's work on conversion and with reference to three verses and the chorus of adele's song as representing voices of more minoritized scholars, i identify four practices to confront frustrated change. institutions who expand their welcome to include more previously underrepresented members-in an effort to become more just, diverse, equitable, and inclusive communities-can fall short of these goals and thereby cut the conversion process short by failing to sustain the hard work of deep change. bringing adele and rambo into conversation, i distinguish four practices that could loosen institutional stuckness in order to motivate institutions who still want to keep moving through a decolonizing conversion process: ( ) untangling initial inclusion from completed conversion, ( ) truth-telling about desires not to convert, or resistances, ( ) detangling toe-dipping from being in over our heads, and ( ) (re)engaging a commissioning call and response in order to (re)commit to conversions in practice. without engaging these practices in an institutional decolonizing conversion process, more minoritized community members are often left to shoulder a disproportionate measure of individual risk. adele's song "send my love to your new lover" can serve as a fresh prophetic anthem for the limits and opportunities for theological schools engaged in a conversion process of transformations in just practice. a conversation between conversion scholar rambo and music superstar adele can lead to recommendations for strategic practices to inspire institutions and we who inhabit them to move more deeply into practicing the best of what is professed. rambo has been writing about conversion for decades. across his abundant scholarship, conversion most simply means change and transformation. while conversion can and often does denote change from one religious tradition and set of practices to a different religious tradition or set of practices, conversion can also mean change and transformation within the same profession of faith. this latter aspect of conversion is my focus, "intensification [that] takes place within a tradition" and its "already available" practices (rambo , pp. , - ) . already complex as institutions, mission and identity statements of theological schools often have a prophetic character and calling, beckoning regular conversation and discernment at individual and institutional levels (van dyk ). how do schools that are committed to mission-driven theological education engage conversion from actual practice more deeply into aspirational mission? such conversion involves interpersonal and intercultural interactions that unfold in both the foreground and background of lived human experiences. what exactly is institutional conversion? what does it involve? and, why is it so difficult? writing during a s rise in religious practices alongside increasing recognition of pluralism, rambo notes how institutional fraying co-exists with freedom to move across diverse religiosities (rambo , p. ) . with resonances with womanist and feminist calls for scholarly accountability also rising in the early s (russell and clarkston ) , studying conversion involves reflexivity, professions of faith, and academic commitments (p. ). by the s, womanist and feminist theologians around the world were calling for conversion as an ongoing "seeing and acting in new ways in a fundamental process of transformation" (oduyoye , p. ) . by the s in pastoral theology, scholars were also paying closer attention to systems, communities, and cultures, now identified as emerging communal-contextual and intercultural paradigms (ramsay ) . as a white woman who is partnered, a mother, a lay united methodist, a u.s. citizen, and an employed academic pastoral theologian with international work experience and teaching and learning commitments across borders of identity and geography, my academic commitments are to pastoral theology's intercultural paradigm, requiring ongoing assessment of practices at intersecting individual, communal, and global dimensions (sharp ) . this is the location from which i read rambo's work. using an interdisciplinary methodology, rambo weaves academic discourses of psychology, anthropology, sociology, and religion with extensive interviews and ethnographic engagement around the world ( , pp. xi-xii, ) . what is conversion? conversion is many things. rather than one hegemonic definition, rambo delineates factors and energies, movements and moments involved in conversion as a process. multidimensional, conversion involves empathy, personal experiences, human predicaments, careful observation within and across cultural contexts, and a deep desire for self-and communal understanding alongside conceptual explanation (pp. xiv, - ) . emotionally complex, conversion can elicit joy, astonishment, release, anguish, turmoil, despair, conflict, guilt, and more, often all at once (p. ). human yearnings, emotions, and moral commitments shape individual and collective discernment through what rambo calls an emerald web of seven stages or periods of change (p. ). in the following paragraphs, i will briefly summarize rambo's seven conversion stages-context, crisis, quest, encounter, interaction, commitment, and consequencesthrough the lens of the interplay between institutional conversion (intensification of already established religious commitment in practice) and embodied individual risks and vulnerabilities. context involves an internal and external "force field of people, events, experiences, and institutions [that] operate on conversion. .. the total environment in which conversion transpires" (pp. , - ) . complex and dynamic, context can dissuade and/or encourage conversion depending on how conversion may meet needs and yearnings within particular contexts (pp. , , ) . context involves large multi-systemic forces and local daily life practices (p. ). context is a great resource for conversion, given that cultures are constantly in motion (p. ) even while tradition and familiarity infuse common resistances to change. rambo acknowledges that "most people say no to conversion" (p. ). contextual factors that make conversion difficult for groups of people include ways in which increasing religious choice is interpreted as a gift and/or threat of pluralism, as a gain and/or loss of identity, as fracturing and/or expanding capacities of persons and communities (pp. , , ) . what would it mean for institutions to enter a process of converting to pluralism, where religious mandates lead to practicing multiple diversities as a creative good (bidwell ; lartey ) ? further, when communal conversion does occur, however incrementally or slowly, how do groups of people reckon with ways that previous practices, even after being renounced and transformed, linger? rambo reminds us that "even symbols. .. directly and explicitly rejected can remain a powerful part of [the] psyche" (p. ). conversion prompts many such conflicts and crises of faith within contexts. crisis, explains rambo, forces "individuals and groups to confront their limitations and can stimulate a quest to resolve conflict, fill a void, adjust to new circumstances, or find avenues of transformation" (p. ). he notes that it can be hard to tell whether crisis precedes and leads to conversion or follows a glimpse of a different way of life than one is accustomed to practicing-or perhaps both (p. ). crisis is co-extant with new possibilities (p. ) as "all conversions implicitly require a leaving-behind or a reinterpretation of some past way of life and set of beliefs" (p. ). quest awakens the resourceful human yearning to make meaning and find life purpose (pp. , ). conversion can be very difficult because it involves grief, loss, sadness, severed relationships, altered rituals, disconnections, dislocations, and more (pp. - , ). "the past," rambo reminds us, "is powerful because that is the world in which we dwelt for years, and it lives on in our minds and hearts. there is no easy escape from the past, no easy transition to the future" (p. ). no wonder conversion also includes a quest for meaning, a yearning to be persuaded that new possibilities will also bring release of tension and increase of joy. motivated by a variety of complex and interacting factors, potential converts turn to communities of support for affirmation of new possibilities that are at once attractive and repulsive (p. ). when it comes to institutional conversions, how long can groups reside in this threshold between recognition of loss and promise of release, and at what cost? can tensions be held collectively rather than foisted on a few? encounter involves negotiations between advocates of transformative conversion and would-be converts who often co-reside in shared and/or overlapping contexts. in encounters, advocates for change meet advocates for remaining (p. ). within encounters, significant wisdom resides with "marginal persons [who] are often the earliest converts to a new movement" that promises to support more justice, meaningfulness, emotional gratification, practical wisdom, leadership, and power (pp. - ). indigenous people, notes rambo, often inhabit models of movement and are culturally pliable as a consequence of both internal commitment and outside force (p. ). within encounters, consulting others only goes so far as each person in such interpersonal dramas must find what is at stake for themselves "to enter personally into this new story, to own it" (p. ). encounters raise issues of trust, diverse affirmations of human dignity, and mutual curiosity, especially in complex institutions where forces of tradition meet forces of innovation. interactions that support conversion processes are mutually educational and therefore particularly important for schools. following encounter, deeper interaction foregrounds learning and hospitality. "potential converts," writes rambo, "learn more about the teachings, lifestyle, and expectations of the group, and are provided with opportunities, both formal and informal, to become more fully incorporated into it" (p. ). rambo points to multiple relationships, rituals, rhetoric, and roles evident in interactions. because conversions are both deconstructive and constructive (p. - ), folks can struggle to speak and represent what is going on in the middle of change and transformation. struggle itself is a persistent theme of conversion and, like many conversion elements, can be cast positively and/or negatively, including struggle between self-awareness and selfdeception. for example, while i have been shaped by reading literature by black women academics such as bambara mentioned above-learning what i've never been required to learn about my need to convert from complicities in oppression-as a white woman, i must both read and learn, never stopping at just reading and quoting. "most white academics," writes antiracist scholar audrey thompson, "do not read widely across races and, even if we do, we tend to use the writings of scholars of color to bolster rather than to interrogate our work" ( , p. ) . beyond mere encounter, conversion interactions challenge and/or affirm role expectations and role enactments (p. ). interactions go deeper. rambo powerfully reminds us that "people who convert and remain the same are not really on a spiritual path of transformation" (p. ). rather, conversion is deep change. highlighting this theme, womanist theologian kelly brown douglas calls institutions to convert in terms of who counts as a full person and to radically expand the notice of place ( ; see sharp where i engage dr. brown douglas' profound work more deeply). a willingness not only to learn but indeed to be transformed by a learning process is required. rambo puts it this way: "the relationship [that supports conversion] is based on one person knowing more and being willing to share it with an interested person who is seeking assistance, who is willing to play the role of novice" (p. ). persons who know more about what needs to be learned do not always have access to teaching roles denoted as more informed. conversion interactions birth new relational networks, new rituals, new ways of speaking and listening, and new roles (p. ). "conversion of hearts is not enough," declares ethicist m.t. davila, commending the kind of learning interaction that will support lasting change. she specifies: conversion of hearts for effective social and structural transformation requires listening to the people and the movements that most clearly call out the forms that structural sin take in today's world. convicted hearts receive extensive training in direct social action and advocacy, and they also engage in ongoing education about the ways the sin of racism continues to dominate many of our political and economic structures today (davila ) . to underscore this point, other scholars had also correlated conversion and role change at the time of rambo's text. also in , ethicist emilie townes published a troubling in my soul: womanist perspectives on evil and suffering, an edited volume that included womanist theologians (townes ) . across the chapters, contributors noted ways in which institutions as currently structured perpetuate structural evil and therefore must be engaged with bold resistance and suspicious ambivalence if and when theological schools and faithdriven institutions seek to be more inclusive. roles in institutions don't shift easily, but they must, argued novelist activist toni cade bambara nearly years ago. why? because we are "abusing each other, aborting each other's nature-in the teeth of experiences both personal and historical that should alert us to the horror of a situation in which we profess to be about liberation but behave in a constricting manner" (bambara , p. ) . she called for conversion from sinful western models that have distorted roles and are in need of transformation and recovery, "irresistible revolution" not outright rejection (bambara , pp. , ; bambara bambara / . conversion interactions negotiate, ritualize, speak about, and embody truth-telling and power. what kind of commitment can support such mutual investment, and how do we know that learning creates lasting change? commitment "is the fulcrum of the change process" (rambo , p. ) . expressed in vows, contracts, covenants, and mission statements, commitment involves both word and deed. practicing commitments, argues rambo, involves decision-making, ritual promises, surrender, testimony, and moral wrestling with motivation (p. ). rambo's training in psychology and religion is helpful as he aptly describes the deep soul wrestling involved in each of these elements of practicing commitments (p. ). decision-making involves reflection on one's own life experiences, listening to and believing the life experiences of other people-both stranger and trusted friend-confronting desires and fears, and negotiating between questions of meaning and practical problem-solving (pp. - ). these practices need ongoing mutual accountability and support because individuals resist change while institutions can fall prey to substituting talk of change for transformed practice (p. ). power and control flow through resistances and accountabilities, with promise and threat continually at play (pp. - ). public profession and communal assessment support a commitment to conversion. often absent from revised mission statements and vows, commitment involves articulating what will be released to make room for changed ways of being. rambo writes that such "surrender requires [a] person to confront directly what [they] will be giving up for the benefits of the new option. this process is never easy. .. anguish is keenly felt" (p. ). while it can take a "leap of faith" to believe, surrender "is the very point at which energy becomes available for a new life" (p. ). on an institutional level, backlash or what sara ahmed ( ) calls brick walls appear just when lasting change seems most promising. why is institutional change so difficult? rambo writes, [o]n a more profound level, surrender . . . continues over a lifetime. it is an inner resolve to shift loyalties, and the process is never complete. old urges return, sometimes with greater power than before. few people experience surrender as a final achievement, without reservations or backsliding. surrender is a process in which the person disconnects [themselves] from old ways and patterns and gradually is able to consolidate the new life into a firmer, growing commitment ( , p. ). space for and ritualization of public testimony remain important beyond any initial commitment or aspirational change. testimony "becomes more than a story of individual change; it also reflects the ongoing process of institutional change" (p. ). in the commitment stage, testimony is a cooperative truth-telling process about how conversion manifests not only the desire to change but also the intention to live into lasting consequences. consequences, according to rambo, are the practiced effects of transformation and change, the living out of conversion experiences over time since "more profound changes may come in the months, and even years, after the initial conversion has taken place" (p. ). for lives shaped by institutions, multiple conversions and multiple consequences unfold simultaneously. rambo suggests practices of accountability around a simple question: what is "the quality of life produced by these institutions" (p. )? one assessment tool used by several institutions is the crossroads anti-racist spectrum for institutions invested in multicultural affirming practices, a whole stage theory within the consequences stage. crossroads' development of practice moves from more exclusive to more inclusive practices described as exclusive ➔ "club" ➔ compliant ➔ affirming ➔ transforming ➔ fully inclusive anti-racist organization in a transformed society (crossroads n.d.). rather than assess total conversion (not that that is likely or advisable), rambo suggests using developmental moments as "lens[es] through which to observe conversion [where] one can make evaluations as to whether the convert has progressed, regressed, or remained the same developmentally as a result of conversion" (p. ). again, his advice to prioritize voices of more institutionally minoritized peoples in all stages of conversion is also relevant here. institutions should find ways to assess quality of work life. where do folks experience deeper relationships, relief from guilt/sin, celebration of communal belonging, better understandings of what is going on, authentic participation in a "profound revolution," and increased courage, security, and peace (pp. - , )? deep and radical transformations take a long time and require multiple conversions; therefore, partnerships of accountability, regular opportunities for public witness and testimony, and periodic assessments of the quality of life together are warranted. rambo's seven interconnected stages slow down discrete moments in a long process of change, thereby showing why conversion can be so very difficult, even undesirable. these stages help organize change among diverse groups of folks and institutions that resist change. the transformative change of conversion, writes rambo, "is precarious; it must be defended, nurtured, supported, affirmed [by and in] community" (p. ). institutions both support and dissuade conversions with processes, policies, and practices that "support systems and suppression, access and repression, encouragement and discouragement" (p. ). yes, conversion is possible and happens all the time "in all directions" (rambo and farhadian , p. ) . and yes, conversion is challenging in the best of circumstances, requiring an ongoing investment in struggle for a purpose. rambo both presents an in-depth study of conversion and invites conversation partners and new resources to contribute to the meaning of conversion and the phenomenon of change. this is similar to what i am doing in this article by highlighting a perhaps unlikely conversation partner, the pop singer adele. while rambo supports understanding conversion as a long-term process filled with as many if not more difficulties and reservations as possibilities and transformations, i have found the lyrics of adele's "send my love to your new lover" help put language to what is at stake for theological institutions invested in long processes of conversion, especially institutions who need to slow down and assess where they are in change processes and who is more and who is less impacted in daily life struggles for transformation. conversion scholars are still calling for expanding conversion studies to account for global forces, to include religious diversities, and to traverse geographies (rambo and farhadian , pp. - ) . theological schools are also trying to be more diverse and inclusive. schools should be able to support mutual learning processes of conversion, yet rambo shows just how much folks in conversion processes often drag their feet in changing bits of tradition, from a meeting time to a convocation program, not to mention practicing radical transformation. turning to the arts may help loosen our collective imaginations in what is at stake given that conversion is such a long and winding process, as rambo helps us understand. rambo invites such studies that highlight that "the importance of culture in shaping persons, communities, and religions must be given more weight in conversion studies" (rambo and farhadian , p. ) . conversion scholar diane apostolos underscores that "as human beings we come to know through our natural and primary aesthetic sensibilities-sight, sound, movement-through icon, image, and illustration, through myth and story, through dance and ritual" (apostolos , p. ). further, she argues that "art impinges upon, narrates, and supports conversion" (apostolos , p. ). regarding the transformative power of art, rambo notes that "the greatest testimony to the power of a work of art is its ability to elicit sustained reflection and engagement on many levels. .. [and] engage us intellectually, emotionally, and spiritually" (rambo , p. ) . as i described in the prelude, it struck me one day in front of a notoriously finnicky copy machine that the lyrics to adele's song "send my love to your new lover" may have such transformative potential. singing since age seven, adele laurie blue adkins grew up humbly in tottenham, london, in a "very big family of a lot of women who did everything on their own" (robinson ) . she transformed from a beloved local hipster singer to an international superstar known for stunningly made-up eyes and an even bolder voice, having already received some of the music industry's highest accolades by age . before long, "[h]er music was the most-requested [sic] in karaoke bars, the most played at funerals, 'the best for nervous flyers,' 'the most popular to fall asleep to'" (lamont ) . after her emotionally raw and resonant albums and (recorded when she was ages and ), adele's album "track[s] personal regrets, broken relationships and dashed expectations with. .. crushing emotional power" (npr ) . in her own words, adele reflects that "my last album was a break-up record and if i had to label this one i would call it a make-up record. i'm making up with myself. making up for lost time. making up for everything i ever did and never did" (adele n.d.) . adele describes seeking a co-writer to help her write what would become "send my love to your new lover" as a quest to have someone bring out of her the song she knew she could sing (npr ) . although written during the aftermath of a love relationship gone bad, this song can also be read to examine other contexts. when read through the lens of stalled institutional conversions to just practices and the inequitable costs involved at the level of individual risk, four practices emerge that i believe could help loosen impediments to practicing the transformative change that theological schools so often profess. in what follows, i will quote a few lines of "send my love to your new lover," followed by a practice these lines suggest and questions they could raise for theological schools invested in transformation. this was all you, none of it me you put your hands on, on my body and told me mmm, told me you were ready for the big one, for the big jump i'd be your last love, everlasting, you and me mmm, that was what you told me untangling initial inclusion from completed conversion process this practice involves the temptation to be lured into believing that conversion can be quick and easy. "conversion," writes rambo, "is very rarely an overnight, all-in-an-instant wholesome transformation that is now and forever" (rambo , p. ) . it is particularly dangerous to think about the start of change as the end of a conversion process. the same institutions that celebrate increasingly diverse students, faculties, staff, and community partnerships can end up being short-term gigs for the most minoritized community members. a celebrated new scholar can arrive, only to leave before long for what is often described in-house as a better opportunity, a better fit, a hundred reasons other than the institution's lack of hospitality to diverse thriving born of structural oppression. there is a difference between admission and retention, outlined poignantly in a forum for theological explorations report that asked theological institutions to consider: "are we measuring what matters? are we asking the right questions? how might we begin to ask questions of our field and institutions that are not only concerned with whether people of color increase numerically, but that also call our attention to whether these growing numbers of students and scholars are thriving vocationally?" (forum for theological explorations ). when schools seek to diversify faculties, expanding who is invited in the door in the first place is a necessary step. however, practices of learning and hospitality also need to pay serious attention to supporting a conversion process that leads to lasting institutional transformation. inclusion is not enough to sustain a more diverse community. understanding an institution's growing pains can be helped by interviewing the people who have left over the past years, listening well and taking seriously what is heard, and being willing to respond in good faith even and especially when the leavings went poorly. i have heard this advice from colleagues in and outside of academia. as adele's lyrics above note, initial inclusion communicates readiness for change but doesn't mean that institutions are ready for ongoing transformation. the above lyrics highlight at least three aspects of conversion as it relates to the burden of individual risk often placed on more minoritized community members in institutions of higher education (muhs et al. ) : ( ) aspirational organizational mission, ( ) responsibility and accountability, and ( ) embodied risks. first, i suggest that "the big one, the big jump" that is "everlasting" is descriptive of an institution's aspirational organizational mission. in hiring processes, search committees often attempt to discern whether a particular candidate is committed to the school's expressed aspirational mission statement. for current faculty, my school ritualizes collective missional recommitment in an annual convocation service in which faculty vow to support the school's aspirational mission, promising to do so with collegiality and integrity. "that was what you told me" can serve as an assessment tool to measure a community's practices in relation to its aspirational mission. the desire for education to be transformative drives mission statements that call on schools to also be constantly transforming, learning, growing, persuaded to the disciplines and accountabilities of lifelong learning. whose fault is it when things go wrong? "this was all you, none of it me" is a difficult charge, painting a stark calculus of responsibility and placing the blame of harm solely on one party. power and privilege can affect possibilities of mutual interactions when assessing desired and demonstrated change and transformation. at the same time, a growing chorus of voices is calling theological schools to dismantle structures of white supremacy that clearly oppress all persons yet can threaten and actually wound more minoritized scholars in acutely embodied ways (e.g., hill fletcher ; james jennings ; sharp ) . who is responsible for the institutional conversion that can and should occur in theological schools committed to lifelong transformational learning? what are the reliable accountability practices when an institution is serious about midwifing change and experiencing conversions in justice and mutual concern? in addition to aspirational organizational mission and an assessment of responsibilities and accountabilities, conversion is also an embodied experience with embodied risks. embodied risks can feel heightened for all in the enticing and terrifying professions of readiness for deep change and transformation, and yet it is simply the case that some bodies bear more risk than others in an institution that carries tenure, rank, salary, and load differences among the employed community and dynamics of grading, vocational discernment, and curricular decisions that determine the boundaries of learning and opportunities for the future between faculty and students. "you put your hands on my body." deep change and transformation of conversion to a more just, equitable, and inclusive community will require paying attention to the embodied risks of a community's made more and kept more minoritized members, putting into place accountable practices that assess and uphold structures of thriving for all persons, and being willing to engage in the difficult yet transformative process of assessing the community's current practices in relation to its aspirational organizational mission statements. truth telling about desires not to convert, or resistances this is a second practice suggested in adele's song lyrics. it is not surprising that an institution with an aspirational, even prophetic, organizational mission falls short in its daily practice. misunderstandings, mistakes, apologies, and wrong turns are all predictable in long processes of conversion that are lasting and transformative. how do people who inhabit institutions remain steadfast in collective commitments, willing to hear and believe what is not working and committed to creating the conditions where all community members can, are expected to, and do thrive? i contend that deep engagement with resistance to change is needed. when i researched empowerment, i quickly realized that recognizing personal and collective investment in disempowerment is a necessary first step to empowerment (sharp ) . change that matters always elicits resistance because it is long and difficult work (pressfield ) . grappling with resistance is important in contexts that can include grueling decision processes where community members who are not thriving due to structural racism and other forms of structural oppression decide to leave in order to survive. rambo notes that conversion requires learning and hospitality. adele goes further. conversion also requires freedom, freedom from oppression and freedom to thrive. institutions more resistant to change constrain avenues of belonging and frustrate the collective labor of teaching and learning that conversion requires. the illusion of change can quickly become more compelling than the long labor of birthing change, including caring for tender newborn practices. across the board, theological institutions across hundreds of association of theological schools member schools desire to be more diverse. hiring pools and invitations of initial inclusion have diversified. yet, retention of historically excluded, more minoritized scholars has not changed much. entire structures must shift along with every practice of the schools. to use a theological metaphor, it's not just pulling up more chairs to an old feast. when the institution and its internal relationships are toxic and wedded to old colonial models based on hierarchies of power, access, and relative worth, the healthiest choice can be to leave or divest and choose to be well, letting go and even forgiving oneself for falling for an institution for falling short ofdesiring to be changed through sustained conversion. i was too strong, you were trembling you couldn't handle the hot heat rising (rising) mmm, baby, i'm still rising i was running, you were walking you couldn't keep up, you were falling down (down) mmm, there's only one way down detangling toe-dipping from being in over our heads this is a third practice suggested by adele's song "send my love to your new lover." once, when i was crossing between two very different contexts and sets of practices, a mentor advised me to remember the feeling of "toe-dipping" because it quickly fades into the illusion of swimming in the deep end when we've not even waded beyond the water's edge. toe-dipping is an embodied experience. as the analogy goes, the water is cold and, for a moment, one's body inhabits the in-between, bordering two realities. it is difficult to sustain toe-dipping and move unless movement is oriented along the water's edge. as heidi park writes, the water's edge is a place of great danger and postcolonial creativity in a world shaped and mis-shaped by borders from shore to wall (park ) . sustaining toe-dipping requires practices of self-awareness, translation, advocacy, and movement across shifting, sometimes militarized ground. sustained toe-dipping, as my mentor advised me, can be an exercise in humility, a posture oriented toward learning and questioning, a place where insight is not blocked by any illusions of having already arrived. yet, staying in toe-dipping unaccompanied by personal, communal, intercultural, and global awareness and learning can lead to a total lack of movement on the one hand or a false narrative of arrival on the other. adele's lines quoted above are illustrative for institutions who desire to be changed while still in early phases of change. the phrase "in over our heads" refers to robert kegan's book of the same title, written around the same time as rambo's text. kegan suggests that the support needed for negotiating the demands of "modern life" have lagged behind the challenges presented by it. "people grow best," kegan writes, "where they continuously experience an ingenious blend of support and challenge" (kegan , p. ) . i can certainly relate to the feeling of overwork, overwhelm, and information overload, and i confront these dynamics in my colleagues, students, and communities. is it possible for institutions of learning to sustain toe-dipping as an irresistible beginning of work instead of a premature conclusion to it? are we really in over our heads in decolonizing and/or resisting change in the institutional life? to what extent? conversion, rambo reminds us, is a long process-the deep end of the work remains on the horizon for many. rambo emphasized "how far someone has to go socially and culturally in order to be considered a convert" (rambo , p. , emphasis in original) . at the beginning of this paper, i made the claim that theological education may be stuck in a long process of conversion (or set of conversions) to decolonized practices of living and learning in communities that support wellness and thriving for the most minoritized community members and by extension for all people. while i join my voices with other theologians calling for such deep change (sharp ) , for the purposes of this paper, artists' definitions of decolonizing conversion processes are illuminating. poet nayyirah waheed puts it this way in her poem "the release": "decolonization / requires /acknowledging / that your / needs and desires / should / never / come at the expense of another's / life energy. / it is being honest / that / you have been spoiled / by a machine / that / is not feeding you freedom / but / feeding / you / the milk of pain ( , p. ). beautifully knitting feeding practices and processes of decolonizing transformation, chef/storyteller/gardener/ land lovers luz calvo and catriona rueda esquibel draw inspiration from indigenous practices to support the theory that decolonization is a multi-layered process of recovery-or set of recoveries. conversion as recovery looks like moving from white supremacies and americanization programs to respect for indigenous knowledge and cultural revitalization, from disavowal to blessing, from thoughtlessness to gratitude, from refined foods to whole foods, from wasteful to resourceful, from advertising and marketing fads to ancestral knowledge and oral tradition, from pesticides and monoculture to permaculture, intercropping, and organically grown, from gmo seeds to heritage seeds, from agribusiness to locally controlled fair trade, from food for profit to food to sustain life, and from assimilation to resistance and resilience ( , p. ) . what could it look like to practice these kinds of multiple conversions within institutional theological education? send my love to your new lover treat her better we've gotta let go of all of our ghosts we both know we ain't kids no more send my love to your new lover treat her better we've gotta let go of all of our ghosts we both know we ain't kids no more . . . (re)engaging a commissioning call and response; (re)committing to converted practices this constitutes a fourth practice suggested by adele's song to support institutional conversion without foisting individual risk inequitably within theological schools. threaded throughout the three verses of this song is the chorus headlined by the song's title. "send my love to your new lover"-the love you had hoped or planned or promised to invest in me but that was not delivered-and deliver it the next time. learn, turn, and give abundantly to the next person; treat them better. adele models this refrain by breaking off a harmful relationship. in her music video for this song, adele recorded versions of singing the song that appear layered on top of each other all at once. the superimposition of multiple images expresses a range of emotions, signaling a complex layering of letting go of the ghosts that haunt relationships and embodying her artistry in a deeper way (bacle ) . extending the above lyrics to the context of institutional change, conversion that lasts recognizes and redresses harmful practices. as a call to conversion, imploring that folks do better next time invites institutions to engage in the work of conversion with accountability to consequences in practice so as not to harm future partners in the work relationship. such commitment could make institutional change irresistible rather than make leaving and stress inevitable. ghosts linger in this process. what relationships with ghosts could best accompany such a shift? what could or would it look like to let go of the stranglehold of ghosts while acknowledging the hauntings that linger as motivations to change? conversion scholars have studied this part of the conversion process. decolonizing conversion into aspirational missions of learning to lead in love for transformation, both possible and precedented, involves "renunciation of cruelty and violence in favor of nonviolence and neighbor love" (rambo and farhadian , p. ). adele sings a simpler yet still difficult song: learn from the past and do better next time. how will we who live and work in institutions know that we are ready to treat each other better? we will know when there are tangible and regular structures of support. when there is a tangible want or need alongside reliable doubt that the current system can support the challenge, transformation is made more possible through accessible and known contextual resources that can support conversion, with barriers to change identified and set apart or satisfied and with change that is implemented (paloutzian , pp. - ) . bringing adele and rambo into generative conversation helps to clarify four practices of conversion for theological institutions who seek and need to change to align institutional practices with aspirational missions. the timing is urgent as schools profess a unified focus on increasing diversity as an institutional priority at the same time that many minoritized scholars still bear greater individual and professional risk in the change process. first, recognize the misunderstanding that the beginning of conversion is not its conclusion. schools can do this by detangling rightly celebrated initial inclusion from the deep practices of learning and hospitality needed for retention and sustained change over time. second, choose to tell the truth about desires not to change, institutional and human resistances that are part of every change process. schools can do this by sharing the responsibility of confronting resistances instead of scapegoating new community members when difficulties arise. third, detangle toe-dipping from being in over one's head. this practice reveals a catch that is part of deep change: forays into real change are embodied experiences and can disorient all community members. however, this initial border-crossing disorientation is not to be confused with swimming capably in the deep end of the work. schools can work on this with dedicated practices of awareness and assessment, often needing sustained outside facilitation. fourth, engage or re-engage a call and response process that recommits to conversion. schools can ritualize ongoing conversions in word and in deed with both public profession and accountability in practice. what could it look like to incorporate ongoing conversion into already existing annual rituals of convocation, commencement, and institutional cycles of self-assessment, performance review, and accreditation? commissioning a reinvestment in conversion is a way for schools to believe in the possibility of conversion even here, even now. these four practices of conversion could help to loosen stuck places in change and share the risk and beauty of change more equitably to support institutional and personal workplace wellness. an enduring question within the study of conversion as change and transformation is the basic question of religious ethics: "what is a human being? is it possible for a human being to change?" (paloutzian , p. ) . i extend this question to ask whether it is possible for a group of human beings to change, why it can be such a difficult and long process, and what is at stake in the process of discerning and engaging this question in practice within institutions of theological education. conversion is a long process with many elements that intertwine individual risk and institutional desire for transformation. as rambo warns, [a]t the same time that a potential convert may be attracted to. .. the new. .., [they] may still be enmeshed in old ways of life. vacillation between two worlds can be very painful. the decision to cross the line into a new life, on the other hand, can be an occasion for tremendous joy, for generating a new feeling of freedom that can itself be a powerful experience confirming the theology being embraced. (rambo , p. ) . as participants in academic pastoral theology and psychology, we are involved in thresholds of life and death, processes of multiple conversions and divestments (streib , p. ). yet institutional conversions are warranted wherever individual risks differ based on intersectional embodied differences such as race, class, ability, gender, citizenship, and more, which are characteristic of so many contemporary institutions that dis/order our lives. harmful institutional structures can themselves become earworms, involuntarily shaping the tunes we hum and believe about how our life together must be organized. adele and rambo can help imagine another way. the stakes are high in terms of living well together. do we want to be well? living a feminist life seeing religious conversion through the arts women in leadership conference presentations adele's send my love to your new lover video: director patrick daughters goes behind the scenes. entertainment weekly on the issue of roles the salt eaters. vintage (contemporaries ed.). new york: vintage books foreword to the first edition when one religion isn't enough: the lives of spiritually fluid people stand your ground: black bodies and the justice of god decolonize your diet take care: notes on the black (academic) women's health forum. the feminist wire crossroads ministry the conversion of hearts and the sin of racism create conditions for scholars of color to thrive the priorities you named the sin of white supremacy: christianity, racism, and religious diversity in america. maryknoll: orbis. hooks, b. ( ). teaching critical thinking the christian imagination: theology and the origins of race in over our heads: the mental demands of modern life adele: 'i can finally reach out a hand to my ex postcolonializing god: an african practical theology contemplation in the midst of chaos: contesting the maceration of the theological teacher presumed incompetent: the intersections of race and class for women in academia conversion psychology of religious conversion and spiritual transformation postcolonializing practical theological methodology as cartography.of boundary dynamics the war of art: break through the blocks and win your inner creative battles the oxford handbook of religious conversion archaeology of memory: personal reflections on de staebler's sculptures understanding religious conversion pastoral care and counseling: redefining the paradigms cover story: adele, queen of hearts dictionary of feminist theologies the psychology of religion, spirituality, and diversity creating resistances: pastoral care in a postcolonial world the living me: unmasking poisonous pedagogies by playing and postcolonializing in pastoral theology decolonizing methodologies: research and indigenous peoples the oxford handbook of religious conversion tiffany, friend of people of color: white investments in antiracism a troubling in my soul: womanist perspectives on evil and suffering the scope of our art: the vocation of the theological teacher educational design: when tweaking the system just won't do. reflective teaching (blog) how do earworms start? classifying the everyday circumstances of involuntary musical imagery (earworms) publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgments i am grateful for and acknowledge the support i received for this paper through conversation with new directions in pastoral theology conference participants, conference respondent kelly bulkeley, lewis rambo, faculty colleagues at columbia theological seminary, and writing group partners. key: cord- -id jg v authors: fouda, ayman; mahmoudi, nader; moy, naomi; paolucci, francesco title: the covid- pandemic in greece, iceland, new zealand, and singapore: health policies and lessons learned date: - - journal: health policy technol doi: . /j.hlpt. . . sha: doc_id: cord_uid: id jg v objective(s): this paper aims at providing an overview of the covid- situation, health policies, and economic impact in greece, iceland, new zealand, and singapore. the four countries were chosen due to their ability to contain the spread and mitigate the effects of covid- on their societies. method(s): we use document analysis based on the available national reports, media announcements, official coronavirus websites and governmental decrees in each of the four countries starting from the (st) of january o the th of august announcements. we apply a policy gradient to compare and examine the policies implemented in the four countries. finding(s): the four countries have different demographic, epidemiological, socioeconomic profiles but managed to control the pandemic at an early stage in terms of total number of positive cases. the four countries managed to absorb the health system shock and decrease the case fatality ratio of covid- . early interventions were crucial to avoid expected life lost in case of no early lockdown. the pandemic triggered several economic stimulus and relief measures in the four countries; the impact or the economic rebound is yet to be fully observed. conclusion(s): we conclude that early, proactive and strict interventions along with leveraging previous experience on communicable diseases and the evolution of testing strategies are key lessons that can be synthesized from the interventions of the four countries and that could be useful for a potential second wave or similar pandemics. in a space of three months, the world has changed quickly as a result of the spread of the severe acute respiratory syndrome coronavirus (sars-cov- ) virus reported in the final days of . to date, only a few countries reported no positive cases within their borders. due to rapid spread and the uncertainty regarding the nature, pathology, prognosis, spread of the virus, and day of confirmed positive cases between different countries, there was no unified regimen to deal with the pandemic on a clinical, social, or economical scale. different countries adopted different measures for detection, treatment, mitigation, and elimination of the virus within their borders. a number of the measures taken are influenced by the existing health care system and its ability to respond to an influx of covid- cases. as a respiratory disease, patients with severe covid- are likely to require intensive care and use ventilators. in addition to focusing on the virus, many countries have considered the societal and economic repercussions of the pandemic and therefore, have provided several economic initiatives to relieve those who are affected and to stimulate the affected sectors. in this paper, we document and compare four countries with different demographic characteristics, health systems, and different varying timelines to combat covid- . the countries greece, iceland, new zealand and singapore have been chosen due to their ability to mitigate the effects of covid- at an early stage and, in the case of one, eliminate community transmission of sars-cov- ; their similar geographic nature as islands and peninsulas; and their economies which mainly rely on service producing industries. the first confirmed cases of covid- in all four countries have varied, singapore reported its first case on the rd of january, whereas the first confirmed cases were almost a month later for new zealand ( th of february), greece ( th of february), and iceland ( th of february). the main objective of this paper is to investigate the health policies implemented by the four countries and to provide insights on the resulted health outcomes and the economic and fiscal impact. we explore the footprints of escalation and de-escalation of measures and policies to contain the pandemic in financial markets as well as macroeconomic indicators. after this brief introduction, the second section provides a country description for the four countries in hand where we look at the demographic profile, health system, healthcare resources, and potential risk factors associated with covid- . the third section describes the methods. the fourth section delves into the results and findings divided as the different trends of covid- in the four countries and policy; technology roadmap based on the available data till the th of august ; the healthcare response data; and the economic and financial indicators and measures. the fifth section is the discussion and conclusion. not only are each of the countries geographically different, but they differ culturally, economically and on a health system level. all of which are likely to have had an influence on how well its population has responded to the spread of sars-cov- . out of the four countries, iceland has the smallest population ( , citizens), whilst greece is the largest ( , , citizens) [ ] . in terms of population size, none of these countries reach the top in the world [ ] . referring to table , greece has the highest population density and old age dependency percentage, the greek population also has the lowest life expectancy at birth however it is above the european average [ , ] . on the other hand, iceland has the smallest population and density with people per km of land, as well as the highest life expectancy at birth. compared to the other countries, singapore has the lowest percentage of old age dependency and the highest population density per km [ ] . . . [ ] . [ ] . [ ] population there are different typologies of health systems between the four countries. for instance, the greek system is a mixed system that includes a predominant social health insurance (shi) system and a supplementary voluntary health insurance (vhi) market. on the other hand, both the new zealand and the icelandic systems are tax-based systems. table shows that new zealand has the highest percentage of health expenditure as a percentage of gdp ( . %) while iceland and greece have a similar percentage, they differ in terms of health expenditure per capita. singapore has the least health expenditure percentage ( %). greece has the highest out of pocket percentage expenditure and the lowest percentage of insured population ( %). service provision in the four countries are mainly from public and also private providers. evidence from countries who have experienced the sars-cov- outbreak for longer suggests that those who have chronic conditions or engage in riskier health behaviors are more at risk from severe consequences of covid- [ ] . in terms of risk factors that might be correlated with the prognosis of the covid- active cases, we look at the prevalence of chronic conditions, tobacco use and alcohol consumption. table shows that greece has the highest percentage of + -year-old population who are daily smokers ( %), while iceland has the least ( . %). as for alcohol consumption, new zealand has the highest number of yearly liters per capita consumed ( . ) . [ , ] tobacco use % . % . % % [ ] percentage of obesity in adults [ ] . % . % . % . % top three conditions as proportion of mortality [ , ] sources: ( )- ( ) containing the spread of sars-cov- has meant implementing a number of initiatives that support the existing healthcare systems within a country. in terms of pre-existing healthcare resources, table shows different parameters to compare the four countries. for example, in terms of number of beds per , of the population, greece has the highest number of hospital beds ( . ). the severity of covid- will mean that a number of intensive care unit beds will be required, out of the four nations iceland has the highest number of beds with . per , people and the highest number of icu beds/ , populations. new zealand has the highest ratio of general practitioners compared to specialists, while greece is the opposite. iceland has the highest number of nurses per , populations. greece has an understaffing issue; the lowest number of nurses per population and the highest number of physicians per , populations; while singapore has the least number of physicians per , populations ( . / , ). [ ] gps to specialist ratio : : : : . [ ] no. of nurses (per , people) approx. . lowest in eu approx. . . . [ ] no. of physicians around . / population highest in eu around . / population . / population . [ ] no. of icu beds / k population in lower than average . / k . / k [ ] . / k [ ] sources: ( )-( ), ( ) . methods the case definition for covid- in new zealand is a person who is unwell with an acute respiratory infection and has at least one symptom of coughing, sore throat, head cold or a loss of the sense of smell. while in iceland, symptoms of covid- are described to be cough, fever, cold-like symptoms, muscle pain, fatigue or sore throats, there have been some instances of abdominal pain and loss of smell and taste. in greece, a case definition for testing if someone shows symptoms such as a fever, cough and difficulty breathing. it is also advised that covid- can present with symptoms of muscle pain, fatigue, and difficulty breathing. at the current stage, testing in greece is restricted to patients with severe acute respiratory illness who are or need hospitalization, as well as patients in hospitals, elderly (> ) care or chronic care, and health staff who develop respiratory infections with fever, coughs or dyspnea [ ] . testing in new zealand can occur through a septum test or nasal swab, and all are expected to self-isolate until the results are confirmed. it is possible that a small number may not be tested and those that are not are still expected to self-isolate. in iceland, initially testing was conducted on residents returning from high risk areas and contacts of confirmed cases. this was widened to include the general community who presented with symptoms, in addition a private testing agency has collaborated with the directorate of health to randomly sample the population. singapore has not released detailed information about the country's testing strategy, in fact the number of tests were released twice in april and have since been reported on a weekly basis. none of the nations have reported an overview of the epidemiology data related to covid- deaths, some of this information is provided in respective nation's media releases however comorbidity information is not included. new zealand, singapore, greece and iceland report information on whether the confirmed cases are in the community or were imported (contracted overseas). new zealand provides information on the flights that the individuals came on, while singapore reports the residency status of confirmed cases. all but singapore are currently reporting information on confirmed cases at a regional level, while confirmed deaths are reported at a national level. there are four periods where greece does not report the daily testing information, the th of march, th of april, rd of june, th to th of june and th of july. the next reported day includes the data for the missing period, for example the th of june reports a , new test increase. to examine the impact of policy interventions on covid- related outcomes, we use the policy categorization process and gradient proposed by moy et al. ( ) . [ ] this categorization process groups policy interventions for those that contain the spread of a virus, interventions for the prevention and care, policies to reduce the economic impact, as well as a categorization for measures taken by private sectors without government intervention and health technology interventions used for treating, testing and tracing cases of a virus. from these categorizations, it is possible to apply a gradient that represents the strictest or most dominant policy being used. to examine the impact of the most dominant policy on outcomes such as the daily rate of cases, we incorporate the gradients into each of the figures in the following sections. . . . daily data covid- cases, deaths, recoveries as of the th of august , greece, iceland, new zealand and singapore had reported , laboratory confirmed cases of sars-cov- between them, accounting for . % of the world's confirmed cases [ ] . out of the four nations, singapore has the most cases with , , whilst new zealand had reported the least with , (see table ). whilst iceland has reported the lowest number of deaths ( ), and greece the highest with covid- related deaths. however, there are numerous differences between the four countries, such as the health systems, interventions put in place and size of the country, that may influence the overall rate and impact of sars-cov- . in order to compare the rates of growth of sars-cov- , and the daily and cumulative trend over the course of the pandemic we revert the date of the first confirmed case to day one. as such we observe that greece, new zealand and iceland are at and days, whilst singapore has reached its th day. the daily number of cases in greece, new zealand and iceland show a fairly normal distribution (see figure ), indicating that the nations are past the peak. in fact, new zealand has announced that it has eradicated the virus from its shores. however, the daily confirmed cases of singapore show a left skewed distribution, as the country had maintained a low number of cases for the majority of the period observed but the number of cases has recently increased. all four countries implemented medium level interventions to contain the spread relatively soon after the first case. containment measures increased in strictness for new zealand at the peak of daily cases, while singapore escalated measures as the daily cases began to increase. economic interventions began to be introduced approximately days after the first case for new zealand, greece, iceland and singapore. it is evident that all countries were experiencing a different daily rate of the virus as the pandemic progresses. to determine the daily rate of change in cases, we divided the daily new cases by the daily new cases from the day before. if the growth rate is higher than one, then the number of cases is increasing and if the rate of growth continues to increase then it could indicate that the policy interventions are not mitigating the spread of sars-cov- . in figure , it is clear that each of the four countries has maintained relatively low daily growth rates, with the biggest spikes in growth occurring in greece towards the beginning of the pandemic, and most recently at the th day. these spikes in greece are likely to be driven by clusters of covid- being discovered. both singapore and iceland have maintained growth rates between zero and three for the duration of pandemic so far. for the last seven days, the average rate of growth for greece, table ). the country with the lowest number of confirmed cases per , was new zealand with per , , however greece also reported cases per , . as observed in figure , the majority of iceland's daily cases were in its fifteenth to fortieth days, whereas singapore's picked up pace towards the seventy-fifth day. despite delaying the number of cases in the wider community in singapore, there was a breakout of cases in the dormitories that house migrant workers. as a result, authorities increased testing in the dormitories and implemented dormitory wide quarantine to stem the spread. note: singapore does not report the daily testing numbers. hospitalization information provides an overview of how note: around the th day singapore reclassified its categorization of hospitals, and a number were moved into isolation. although sars-cov- virus is indiscriminate in those that can catch it, covid- appears to severely affect those over the age of more than other age groups, whilst children seem less likely to catch the virus. each of the four countries provide data on the distribution of covid- by different age groups and gender, although singapore stopped providing age and gender for confirmed cases from the th of april. as of the th of august (see table ), more females (males) were confirmed with sars-cov- than males (females) in new zealand (greece). this equates to male confirmed cases per , , with and confirmed male cases per , and and confirmed female cases per , in new zealand and greece, respectively. [ ] in terms of the distribution of laboratory confirmed cases by age group, all but singapore have released up to date information. however, as each country uses different age group scales the following section reports the total counts for the th of june and does not convert to a comparable population level. referring to figure , the majority of cases in all three countries are in the working population (considered the - age group). whilst the least number of confirmed cases appears to be in children and youth. each nation has reported a number of cases in the over age group, who are considered to be the most at risk. note: singapore has not released a breakdown of deaths, although some information is released in the singapore government's daily media releases. this figure demonstrates the associated deaths, as such this figure refers to the associated deaths and reports more for iceland. all four countries have reported information on the number of deaths and the corresponding ages of the deceased. whilst this is not necessarily released on the dashboards, government media releases specify the ages (or age group) of those who have passed and tested positive for finally, whilst research has indicated that pre-existing morbidities are related to increased severity of symptoms and higher probabilities of death, limited information has been reported by each country on the pre-existing health status of those who test positive for covid- . a limited amount of health-related information is available on the deceased based on media announcements by the ministry of health in singapore. it was reported that ten of the covid- related deaths had pre-existing conditions that were related to cancer, chronic heart disease, diabetes, hypertension, hyperlipidemia, isometric heart disease and kidney disease. seven of the associated cases had multiple morbidities [ ] . in order to estimate changes in mortality risk determine the benefits of public health and environments policies, the estimates of life-years saved by these policies is used as a measure of mortality risk. [ [ ] . in panel b of figure , we see the distribution of government intervention based on the government response index created by [ ] . both demonstrate the increased government activity used to control or stop the spread of the virus. referring to panel a, we see that a majority of interventions are observed after the th case for new zealand, greece and iceland. however, singapore implemented hygiene and border control measures swiftly, before focusing on tracing contacts of confirmed cases. in addition, singapore implemented fines up to $ , and months in prison for breaking quarantine. in comparison to the other three nations, singapore has focused on the use of technology to help manage the spread and increase citizens' awareness of crowded places and social distancing measures. whilst new zealand and greece locked down earlier than most nations relative to the amount of cases (see figure ) , iceland never declared a full lockdown instead the number of people able to meet was restricted (maximum of ). rather there was a focus on containment and protecting health systems before implementing stimulus packages. iceland utilized private industry and created a testing policy for anyone to be tested free of charge, providing the most detailed spread of the disease outside of the diamond princess case study [ , ] . in all nations, the number of hospitalized cases has not overwhelmed the existing health care system, however there are a number of healthcare workers being affected by the virus in terms of confirmed cases and self-isolation as a result of being in contact with confirmed cases. singapore has reported a number of confirmed cases of healthcare staff through their media announcements, with confirmed cases amongst their health staff as of the th of april [ ] . new zealand reported on the th of april that healthcare staff members were isolating and a further had recovered. however, iceland is the only country out of the four that has provided daily updates on the number of staffs in self-isolation and quarantine (see figure ) [ ] . whilst all four countries' health systems have responded well to the virus, all are preparing for potential increases in cases that are beyond their existing health systems capacity. in fact, in response to the covid- outbreak, the greek government announced an increase in the number of permanent medical staff and the intention to reach intensive care unit beds per , of the population [ ] . the government has aided this goal by providing million euros for health resources, and an additional million euros to hire additional health staff. since then, almost , medical staff have been made permanent [ ] . greece has also begun to reduce the lockdown measures and allow certain systems to reopen, at the same time the nation is also preparing resources for an eventual surge of covid- and influenza cases in the fall of . in singapore, the government is increasing its ability to bring online additional icu beds if they become needed. at present, singapore has vacant icu beds, with an additional able to be brought online. there are additional plans in place to bring another online within the next few weeks [ ] . in addition, general isolation beds have increased from to , beds since january and the national centre for infectious diseases has increased their negative pressure isolation beds from to over [ ] . to increase the health staff capacity of the public health system, the government launched the sg healthcare corps on april th for private healthcare professionals to sign up. as of the th of april, an additional , health care professionals had registered [ , ] . those who show milder symptoms and are on the path of recovery from more severe symptoms of covid- are placed in community care facilities in singapore. to care for these individuals, singapore created , beds in a number of facilities across the country. for those individuals who are recovering well and are healthy at the -day mark of the course of covid- , they are moved to a community recovery facility to stay where they are then assessed for discharge [ ] . singapore has , recovery beds and will be expanding it to more than , beds by the end of june [ ] . as well as these facilities, singapore has created swab isolation facilities (totaling , beds) where those who are unable to self-isolate can stay whilst they wait for their test results to come back [ ] . other measures have been taken by the four countries to help facilitate the movement of medical resources, such as the easing of importers licenses for medical protective gear in singapore [ - ]. we can also observe that the consumer confidence indices in these countries have hit their lowest since the beginning of . similarly, business confidence indices in these countries decreased during the pandemic given the covid- outbreak has brought the economy across the four countries to a standstill. in figure , we see the impact that the pandemic has had on the retail and tourism industries. except supermarkets and consumable sectors, the turnover in other sectors has fallen since february . this is explained by the majority when it comes to discretionary spending, it is clear that individuals have reduced their purchases throughout the pandemic as a result of the high level of uncertainty and unemployment rate. tourism has been heavily impacted by government interventions causing an incredibly low number of foreign visitors, with more than % decrease compared to the same period in . such a drop in a sector clearly indicates there is a need for continuous support for the workers and business in the tourism industry. as a part of this, job keeper and job seeker support packages should be fairly distributed among the hardest hit businesses such as the tourism industry. figure demonstrates weekly job seeker support or the cumulative wage subsidy as well as the community activity of new zealand. due to the easing in the restrictions, where the majority of businesses have started opening, we see that the subsidies provided by the new zealand government flatten during may . in addition, we can see that various activity indices, including card transaction spending, electricity grid demand, and traffic indices, have been normal after re-opening the economy. the only noticeable exception is in singapore where the curve of the total positive cases showed an exponential pattern from day onwards. this is due to the outbreaks in the country's migrant dormitories, which are densely populated and difficult to socially distance in. in addition, greece has seen a steady although small increase in numbers which may be due to the increase in testing and a more widespread testing strategy. iceland also announced plans to implement nationwide testing which is easier to implement in iceland due to the small population number. the four countries maintained a low case fatality ratio (cfr) with singapore having the lowest cfr of . %. it is noticeable how singapore has the lowest cfr and the lowest deaths per , regardless of the fact that it has the least health expenditure as percentage of gdp. this might be primarily attributed to the readiness of the health system for such events based on the experience with previous pandemics like sars and h n . additionally, this low cfr could be attributed to early intervention by the singaporean government. as shown in figure , singapore initiated its response days prior to the detection of the first positive case; the response included advice for wuhan-bound travels and a temperature check in sea checkpoints and airports. greece has the highest cfr with . % but compared to other european mediterranean countries such as italy, spain, france, and turkey, the greek cfr remains relatively lower. compared to the four countries, the high cfr could reflect the high old age dependency as shown in table and could also reflect the fact that the positive cases are higher in older age groups compared to the other three countries as shown in figure . additionally, the high cfr in greece could be related to the testing strategy, which focuses on severe cases. iceland has the highest number of deaths per , populations among the four countries and this is mainly due to the small population number and the fact that the number of confirmed cases is concentrated in the younger age groups as shown in figure . the mitigation policy interventions as shown in table and figures , , , and , show that the early policy interventions as seen in singapore and the strict early policies as seen in greece, iceland and new zealand might also be correlated to the relative low number of positive cases and deceased cases at early stage of covid- . this is also reflected in the low number of hospitalizations and icu admissions in the four countries in figure . this indicates that the health systems of the respective countries managed to absorb the influx of new cases without reaching full capacity/saturation. in addition to the pandemic's impacts on health systems, the economic and financial impact in the four countries is ostensible. several measures and policies implemented by the four countries along with their economic and fiscal responses in order to contain the pandemic. the economic and fiscal measures implemented by the four countries resulted in immediate relief for relevant stakeholders however, the assessment of the full effect will need a longer time period to observe amidst the covid- -related economic hardships. despite all economic and fiscal support packages provided by these countries, we can observe that the major market indices have recently started moving smoothly across four countries. however, we see a significant drop in exports and imports by the four countries that signals the break in the global supply chain. if this continuously happens, we will ultimately see the increase in unemployment and inflation rates and gdp will collapse. the covid- pandemic has also hit the consumer and business confidence indices, thus, neither consumers nor businesses feel safe during such a tough period. due to the high level of uncertainty amid the covid- pandemic, the local exchanges have depreciated compared to the us$ dollar, which can be related to the boost in the demand for us$ given its safe-haven status. on the other hand, short-and long-term government bond yields have hit their lowest in spite of their lower risk compared to other securities such as equity stocks. however, these countries hope to recover the damage by providing continuous support and implementing existing policies. these measures will get employees back to their jobs, guarantee their wages and salaries, and boost the economy. important lessons can be learned from the management of the covid- pandemic in the four countries. firstly, building upon previous experience and capacity to respond to future pandemics as shown in the singaporean experience. secondly, the early and strict policy interventions to combat the spread of the pandemic within borders as seen in the greek and new zealand case. thirdly, the proactive and responsive policy intervention since day one of the infection globally as seen in singapore. fourthly, the evolution of the testing strategy to a nationwide approach to detect cases at an earlier stage and prevent serious complications. regardless of the differences in the demographic, epidemiological, health system profile, some of these lessons can be applied even in countries with larger borders, bigger populations, or less stable economy. as the four countries have unfolded their exit strategy to the new normal, ongoing/future research should observe the developments and the indicators for a potential second wave and the concurrent health system and economy performance. world health organisation. who director-general's opening remarks at the media briefing on covid- - world health organisation -speeches health system review statistics iceland. 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and protective gear key: cord- -oya fc d authors: fuentenebro, pablo title: will philanthropy save us all? rethinking urban philanthropy in a time of crisis date: - - journal: geoforum doi: . /j.geoforum. . . sha: doc_id: cord_uid: oya fc d in the wake of the covid- pandemic, philanthropy has been quick to react to the call for help from governments and international organisations. and yet, despite the overwhelming response, increasing attention has been brought to the intricate ways in which philanthropists and billionaires have been asserting their presence through their actions and influence in different spheres of power. in this commentary, i challenge the idea that philanthropy can be the solution to all of our problems, and highlight some of the problematic issues that emerge when philanthropy is put at the forefront of the discussion. also, i point out to other elements that have been left out, including the wave of collective solidarity that has been channelled through mutual aid groups and organisations. in the wake of the covid- pandemic, billionaires, celebrities and philanthropy at large were quick to react, organising local and international campaigns to mobilise funds and put the spotlight on a global health issue that, as we would only come to realize much later, most governments outside asia were too slow to react to: from the initial $ million donated by the bill and melinda gates foundation, to the $ . million by jack ma -former ceo and founder of e-commerce portal ali baba-to the $ billion pledged by twitter ceo and cofounder jack dorsey, the list of donations, pledges and commitments made by the super-rich read almost like forbes' top billionaires list. and even those who donated "smaller amounts", like the initial $ million pledged by amazon founder jeff bezos -an estimated . % of his $ bn wealth-were equally called out for giving too little (neate, ) . while many of these donations were aimed at medical research and international organizations, such as the world health organization (who), a large part of the funds and initiatives also focused on cities. this should not come as a surprise, as it is precisely in (some) urban centres where the pandemic had its worse effects: from madrid to london to new york, local and national governments were overwhelmed by the rapid propagation of the virus and the soon-to-follow catastrophic economic impact. and yet, despite the praise the philanthropy world has received for its response to the crisis over the past several months by many media outlets, increasing attention has been brought to the intricate ways in which philanthropists and billionaires have been asserting their presence and influence in the current reality and the post-covid world that will come out of the crisis (gold and robinson, ; teachout and garofalo, ) . for the past couple of decades, geographers and urban scholars have increasingly been paying attention the role of the "super-rich" in society. as jonathan beaverstock et al. ( ) argued in this journal in the early s, "geographers seem to have little to say about the contemporary super-rich, despite their evidential role in shaping the global economy" ( , ) . ever since, geographers and urban scholars have been looking in more detail at the role of the superwealthy across a wide range of geographic viewpoints (see, for example, the volumes edited by hay, ; hay and beaverstock, ) . one of the aspects that has received less attention by scholars are the geographies of "super-philantropy" and, in particular, the wave of multi-billion donations made by high net worth individuals (hnwi) to different pressing issues, from health to education or the arts (but see hay and muller, ) . although by no means philanthropy and charity is something new, as i will cover in more detail below, the vast amount of giving at the present moment does represent a turning point in what has been referred to as the new "golden age" of philanthropy (dobrzynski, ) . in the case of the covid- pandemic, while it would be hard to deny that philanthropy has supported or, at times, filled in a vacuum left by local (and even) national governments -providing resources and funds to cities and community-based organizations-often times the ways in which such engagements and partnerships have been articulated has raised a number of questions on the role of philanthropy in urban governance (sandler, ; teachout and garofalo, ) . in this brief commentary i want to address some of the conflicting arguments around the implications of working with philanthropic institutions or hnwi, particularly at a time when the urgency of the covid- situation has often pushed aside public scrutiny or accountability. in this sense, the following points about the role of philanthropy in the wake of the current crisis are worth bearing in mind. first coined by the economist in the early s to describe the "new entrepreneurial approach" used by individuals seeking to obtain "social returns" through strategic investments in aid programs (the economist, ; bishop & green, ) , philanthrocapitalism as a concept (and all that entails) needs to be questioned as much as ever. despite all the hype and attention the term has gathered for the past couple of decades, there is nothing really new about the "novel" tools used by philantrocapitalism per se: as british sociologist linsey mcgoey has argued, the idea of social return or measurable results was already at the core of modern th and th century philanthropy practised by john d. rockefeller iii, andrew carnegie and many others (mcgoey, ) . the actual point of departure, as mcgoey points out, lies in the vast sums of money spent on philanthropic endeavours (mcgoey, ; ; levenson kehoane, ) . in the united states alone, over the past years charitable giving increased from $ billion per year to over $ billion in . far from being a western phenomenon, philanthropy is also present and equally growing in many other places. the second main characteristic about the "new philanthropy" is the explicit way in which the "opportunities for private gain" have been brought forward by those behind major philanthropic investments (mcgoey, , ) . while in the past, the motives for those embarked in philanthropy may have remained in the background, today self-interest and personal agendas are being touted as one of motivations by those who decide to invest in philanthropy. another problematic idea that needs to be addressed is the assumption that philanthropy "is something everyone can do" and not an endeavour limited to an exclusive club of wealthy individuals. this assertion that has been repeated over and over in recent months by professionals from the philanthropy world, together with the seemingly unequivocal assumption of the collective value of philanthropy for society, especially in times of crisis (sullivan, ; tarasov, ) . for example, in a guest contribution in inside philanthropy a director at rockefeller philanthropy advisors made the following remarks, philanthropy is criticized for being the preserve of the ultra-wealthy and for giving private individuals or organizations an outsized influence in defining what constitutes a public good and the best ways to deliver it. these arguments question philanthropy's social compact, which is an explicit or implicit agreement with key stakeholders about the value it creates in society. social compact also encompasses the concepts of public trust and legitimacy, as well as how philanthropy approaches the transparency and accountability that underpin its legitimacy (tarasov, , unpaginated; my emphasis) i would argue that it is precisely this "social compact" that needs to be questioned and even challenged in the first place, and consider whether philanthropy is not actually contributing to the current status quo. as mcgoey ( ) has bluntly argued, "perceptions of the indispensability of philanthropic initiatives are strengthened as a direct result of their very inability to meet stated objectives. the solution to failed philanthropy is more of it; the failure of philanthropy is its success" ( , ( ) ( ) . along this same argument -and although beyond the scope of this paper-it is necessary to point out to the increasing body of literature that in recent years has been questioning one of the founding myths behind philanthropy, this is, that it leads to a re-distribution of wealth, with the evidence pointing rather in the opposite direction (see reich, ; mcgoey, ; hay and muller, ) . also, and contrary to the argument that philanthropy is something anyone can contribute to, it is interesting to note that, while total philanthropic spending has increased for the past several decades, in the case of the united states, for example, the actual number of people giving to charity has declined in recent years. philanthropy is also a volatile sector and equally vulnerable to economic crises, despite the headlines made by multi-million donations in recent months. during the economic crisis, for example, charitable donations in the united states declined by . % in , and an additional % in (rooney and bergdoll, ) . as such, we will need to be mindful that despite the large sums that millionaires have put on the table for the covid- epidemic, a continued and sustained effort will be needed in order to support those groups, charities and programs that depend on philanthropic investments or, perhaps, rethink what kind of relationship does society and cities want have with the super-rich going forward (more on this later). for, the same way that wealth keeps concentrating on those at the very top, super-philanthropy has become a by-product of such wealth accumulation. there are some obvious implications, namely, that philanthropy risks turning into an investment (and marketing) tool for a select club of billionaires and benefactors who, at the end of the day, will get to decide and influence a wide range of issues ranging from education, to climate change to reproductive health issues or event city planning. from the beginning of the crisis we have seen a different form of collective action emerge from society and regular citizens: from doctors and nurses producing home videos of how to make their own ppes from trash bags and cling film, to soup kitchens and food banks run by neighbourhood associations and community groups, a wide display of generosity and shared solidarity has taken shape across cities in the us, the uk or spain, very different from the large and mediated fundraising campaigns organized by celebrities and the like (solnit, ; tolentino, ) . all these initiatives have relied on the common principle of "mutual aid", a concept first developed as a political idea by the russian philosopher peter kropotkin in the early th century, but which in recent it is worth noting that as the world heads to an economic recession of unknows proportions, the net worth of those at the very top has continued to grow at a steady pace: as forbes recently reported, by the end of may the top billionaires were worth "$ billion more than when the u.s. stock market hit a mid-pandemic low on march ", including the owners of facebook (mark zuckerberg) and amazon (jeff bezos), whose shares have gone up % and % respectively in this lapse of time. to put this in context, in the -month period from march through may , jezz bezos' net worth increased by %, this is, $ billion. as of today bezos's estimated total net worth is $ billion (ponciano, ) . times has been used to describe the shared form of solidarity bringing people together, especially during hard times. speaking within the context of the covid- crisis, american writer rebecca solnit recently explained the way in which the terms has evolved and being embraced by a broader spectrum of society, a dozen years ago, the term "mutual aid" was, as far as i can tell, used mostly by anarchists and scholars. somehow it has migrated into general usage in recent years and now, in the midst of the pandemic, it is everywhere. mutual aid has generally meant aid offered in a spirit of solidarity and reciprocity, often coming from within struggling communities, empowering those aided, and with an eye towards liberation and social change (solnit, , unpaginated) . solnit is one of the authors who has written more extensively about the idea of mutual aid and shared solidarity in the wake of disasters: in a paradise built in hell ( ), she provides with a detailed account of multiple instances when such shared solidarity has taken shape: from the lisbon earthquake to the hurricane katrina in new orleans, almost every time a natural (or man-made) disaster has struck, people have managed to come together and support each other through collective action driven by a shared sense of responsibility. and yet, somehow, the stories of people's generosity, resilience, and creativity in the wake of the current pandemic have gotten somewhat muddled or thrown into the same bag as philanthropy. while there is no denying of the influence and the "star-effect" of celebrities and high net worth individuals to fund raise, it is very important that we differentiate between these headline-making campaigns from the regular, every day actions of anonymous individuals, and their power to organise and reach out to one another, whether that be doctors, nurses or workers in the food industry. it is necessary that we make this distinction for, as obvious as it may seem, over the past few months we have been hearing again and again that "philanthropy can bring people together" through "individual acts of kindness" (maurrasse, , unpaginated) . i would argue, however, these "act of kindness" are not philanthropic actions but mutual aid at its core, specially seeing the context in which all these groups and collective efforts emerged from: it is important to note that, from its origins, the idea of mutual aid included an element of protest and rebellion, and that is something that should be taken into consideration when looking at the differences between philanthropy (and charitable giving) and collective action. as jia tolentino points out, "both mutual aid and charity address the effects of inequality, but mutual aid is aimed at root causes-at the structures that created inequality in the first place" ( , unpaginated) . in many ways if should not come as a surprise that many of the stories about mutual aid and support networks have come from the united states, for all these networks and examples of altruism and generosity also speak out to the systemic failure of a system that has left those most in need behind. i will be returning to this idea in my conclusion. as such, we need to be vigilant that mutual aid is not conflated with philanthropy for, at their core, they speak to different causes and, equally important, they seek to solve a different set of problems. the exceptional situation caused by the covid- crisis has led to a decline of public scrutiny and accountability of decision makers, including local governments. cities, local and national governments seemed to have surrendered to (private) philanthropy in order to implement measures, without any form of public consultation: new york state governor andrew cuomo announcement in mid-may to form a new partnership with the gates foundation to "reimagine education" -challenging "the old model of everybody goes and sits in the classroom" -caused great unease and controversy in the education sector over the use of technology, privacy and resources in an already underfunded school system, especially in the wake of previous failed projects endorsed by the gates foundation in ny state (strauss, ; teachout and garofalo, ) . equally, cuomo's decision to enlist former google ceo eric schmidt to head a commission to "reimagine new york" post-covid was met with great scepticism by local officials who regarded with scepticism the role of wealthy private individuals in what should be a public decision process (sandler, ) . in the case of madrid, the president of the region isabel díaz ayuso underwent much criticism when she unilaterally chose three fast-food chains to deliver school meals to children from low income families during the covid- lockdown imposed by the spanish government. despite being questioned by health experts, opposition parties and families for what was seen as an unhealthy and cost-saving measure, díaz ayuso argued that the urgency of the situation gave her no choice. eventually, after almost two months of feeding hamburgers and pizzas to the kids, the president gave in to the complaints and decided to cancel the deal with the fast-food providers (ferrero, ) . citing the urgency of the situation, measures like this have been adopted or passed by local (and national) governments in many countries around the world, often cases in the form philanthropic engagements. when recently discussing the role of philanthropy in the covid- crisis, new yorker former mayor and billionaire mike bloomberg argued that "philanthropy can't replace the efforts of national governments on a challenge as massive as the coronavirus pandemic (…) but it can support and augment those efforts, and help fill in gaps, and that's what we're doing" (sullivan, , unpaginated) . yet it is precisely those gaps we need to be more vigilant about. looking ahead, it is hard not to cast a sombre outlook of the world that is yet to come. at the risk of being overly provocative, i would like to return briefly to philanthropy's so-called "social compact", and the (increasingly challenged) notion that philanthropy creates value in society. although this is not a new debate, we should take issue way in which philanthropy as something universally good is being repeated again and again like some sort of mantra. i find very problematic the way in which philanthropic institutions, or the individuals that represent them, argue that philanthropy will solve humanity's problems when, for over two centuries, we have seen those problem persist or being exacerbated. also, at stake here is the way in which, in many cases, the story has become about philanthropy, and not about the structural issues it seeks to address. as hay and muller have argued, perhaps it is time we ask ourselves about "the extent to which superphilanthropy is diverting attention and resources away from the failings of contemporary manifestations of capitalism" (hay and muller, , ) . it is perhaps no surprise then that mutual aid has emerged with such intensity in the united states and other parts of the world, not only as a response to a tragic health, social and economic disaster but also in the wake of the failure of national governments and society as a whole to react and act upon underlying structural problems that have persisted for generations. as we are all aware of, the recent demonstrations and protests that have shaken the united states in the wake of george floyd's murder at the end of may speak not only to police brutality but to decades of structural racism, inequalities and injustices sweeping american cities (and many other places) for the past several decades. in a recent online segment, comedy central daily show host trevor noah made a very poignant analysis about the wave of unrest and urban violence taking place across the united states. as noah argues, once the social contract that binds us together as a society has been broken and violated by those same individuals whose job is "to serve and protect" us, what stops us from breaking that contract? as noah expresses it, when you see george floyd on the ground, and you see a man loosing his life in a way no person should have to loose their life -at the hands of someone who is supposed to enforce the law-what part of the contract is that? and a lot of people say, 'well, what good does this do?' yeah, but what good doesn't it do? that's the question people don't ask the other way around. 'what good does it do to loot target? how does it help you to loot target?' yes, but how does it help you to not loot target? (noah, , min. - ) . it is in this context that we need to ask ourselves not only what we ought to expect, but also but we should expect from those in positions of government, power or influence. and this includes as well philanthropic organizations, and the individuals who run them and fund them. the connected cities lab receives funding from a number of philanthropic institutions including the open society foundations, robert bosch foundation and fondation botnar. this paper was independently funded and carried out via the university of melbourne. covid- : lessons for an urban(izing) world getting away with it? exposing the geographies of the global super-rich philanthrocapitalism: how giving can save the world philanthropy now. diversity and creativity for changing times. carnegie reporter el caso de los menús de comida rápida de ayuso: la historia de una rectificación he's to blame for new york's coronavirus catastrophe. the guardian geographies of the super-rich questioning generosity in the golden age of philanthropy: towards critical geographies of super-philanthropy the rise and (potential) fall of philanthrocapitalism, slate magazine the role of philanthropy during the coronavirus pandemic. state of the planet the philanthropic state: market-state hybrids in the philanthrocapitalist turn philanthrocapitalism and its critics trevor noah on george floyd, amy cooper & racism in society call for super-rich to donate more to tackle coronavirus pandemic, the guardian the world's richest billionaires have gained nearly $ billion in just two months we're in a prison': singapore's migrant workers suffer as covid- surges back. the guardian a failure of philanthropy: american charity shortchanges the poor, and public policy is partly to blame what happens to charitable giving when the economy falters cuomo faces backlash for enlisting billionaires eric schmidt and bill gates to 'reimagine' ny after reopening the way we get through this is together': the rise of mutual aid under coronavirus. the guardian a paradise built in hell: the extraordinary communities that arise in disaster cuomo questions why school buildings still exist -and says new york will work with bill gates to 'reimagine education'. the washington post how philanthropists are helping during the crisis. the new york times in a moment of crisis, philanthropy is showing its unique value. inside philanthropy cuomo is letting billionaires plan new york's future. it doesn't have to be this way. the guardian the birth of philanthrocapitalism, the economist what mutual aid can do during a pandemic. the new yorker many thanks to michele acuto and the geoforum editors for their helpful comments and feedback. key: cord- - utunid authors: eikenberry, steffen e.; mancuso, marina; iboi, enahoro; phan, tin; eikenberry, keenan; kuang, yang; kostelich, eric; gumel, abba b. title: to mask or not to mask: modeling the potential for face mask use by the general public to curtail the covid- pandemic date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: utunid face mask use by the general public for limiting the spread of the covid- pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. we develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. model simulations, using data relevant to covid- dynamics in the us states of new york and washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of covid- and decrease peak hospitalizations and deaths. moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. hypothetical mask adoption scenarios, for washington and new york state, suggest that immediate near universal ( %) adoption of moderately ( %) effective masks could prevent on the order of -- % of projected deaths over two months in new york, while decreasing the peak daily death rate by -- %, absent other changes in epidemic dynamics. even very weak masks ( % effective) can still be useful if the underlying transmission rate is relatively low or decreasing: in washington, where baseline transmission is much less intense, % adoption of such masks could reduce mortality by -- % (and peak deaths -- %), compared to -- % mortality reduction in new york (peak death reduction -- %). our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. the community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high. under the ongoing covid- pandemic (caused by the sars-cov- coronavirus), recommendations and common practices regarding face mask use by the general public have varied greatly protect against droplets/aerosols and viral transmission, but experimental results by davies et al. [ ] suggest that while the homemade masks were less effective than surgical mask, they were still markedly superior to no mask. a clinical trial in healthcare workers [ ] showed relatively poor performance for cloth masks relative to medical masks. mathematical modeling has been influential in providing deeper understanding on the transmission mechanisms and burden of the ongoing covid- pandemic, contributing to the development of public health policy and understanding. most mathematical models of the covid- pandemic can broadly be divided into either population-based, sir (kermack-mckendrick)type models, driven by (potentially stochastic) differential equations [ , , , , , , , , , , ] , or agent-based models [ , , , , ] , in which individuals typically interact on a network structure and exchange infection stochastically. one difficulty of the latter approach is that the network structure is time-varying and can be difficult, if not impossible, to construct with accuracy. population-based models, alternatively, may risk being too coarse to capture certain real-world complexities. many of these models, of course, incorporate features from both paradigms, and the right combination of dynamical, stochastic, data-driven, and network-based methods will always depend on the question of interest. in [ ] , li et al. imposed a metapopulation structure onto an seir-model to account for travel between major cities in china. notably, they include compartments for both documented and undocumented infections. their model suggests that as many as % of all cases went undetected in wuhan before travel restrictions took effect on january , . they additionally estimated that, on a per person basis, asymptomatic individuals were only % as contagious, yet were responsible for % of new infections, given their increased prevalence. the importance of accounting for asymptomatic individuals has been confirmed by other studies ( [ ] , [ ] ). in their model-based assessment of case-fatality ratios, verity et al. [ ] estimated that - % of cases went unidentified in china, as of february , , while in the case of the princess diamond cruise ship, . % of individuals who tested positive for covid- were asymptomatic [ ] . further, calafiore et al. [ ] , using a modified sir-model, estimated that, on average, cases in italy went underreported by a factor of , as of march , . several prior mathematical models, motivated by the potential for pandemic influenza, have examined the utility of mask wearing by the general public. these include a relatively simple modification of an sir-type model by brienen et al. [ ] , while tracht et al. [ ] considered a more complex seir model that explicitly disaggregated those that do and do not use masks. the latter concluded that, for pandemic h n influenza, modestly effective masks ( %) could halve total infections, while if masks were just % effective as source control, the epidemic could be essentially eliminated if just % of the population wore masks. we adapt these previously developed seir model frameworks for transmission dynamics to explore the potential community-wide impact of public use of face masks, of varying efficacy and compliance, on the transmission dynamics and control of the covid- pandemic. in particular, we develop a two-group model, which stratifies the total population into those who habitually do and do not wear face masks in public or other settings where transmission may occur. this model takes the form of a deterministic system of nonlinear differential equations, and explicitly includes asymptomatically-infectious humans. we examine mask effectiveness and coverage (i.e., fraction of the population that habitually wears masks) as our two primary parameters of interest. we explore possible nonlinearities in mask coverage and effectiveness and the interaction of these two parameters; we find that the product of mask effectiveness and coverage level strongly predicts the effect of mask use on epidemiologic outcomes. thus, homemade cloth masks are best deployed en masse to benefit the population at large. there is also a potentially strong nonlinear effect of mask use on epidemiologic outcomes of cumulative death and peak hospitalizations. we note a possible temporal effect: delaying mass mask adoption too long may undermine its efficacy. moreover, we perform simulated case studies using mortality data for new york and washington state. these case studies likewise suggest a beneficial role to mass adoption of even poorly effective masks, with the relative benefit likely greater in washington state, where baseline transmission is less intense. the absolute potential for saving lives is still, however, greater under the more intense transmission dynamics in new york state. thus, early adoption of masks is useful regardless of transmission intensities, and should not be delayed even if the case load/mortality seems relatively low. in summary, the benefit to routine face mask use by the general public during the covid- pandemic remains uncertain, but our initial mathematical modeling work suggests a possible strong potential benefit to near universal adoption of even weakly effective homemade masks that may synergize with, not replace, other control and mitigation measures. we consider a baseline model without any mask use to form the foundation for parameter estimation and to estimate transmission rates in new york and washington state; we also use this model to determine the equivalent transmission rate reductions resulting from public mask use in the full model. we use a deterministic susceptible, exposed, symptomatic infectious, hospitalized, asymptomatic infectious, and recovered modeling framework, with these classes respectively denoted s(t), e(t), i(t), h(t), a(t), and r(t); we also include d(t) to track cumulative deaths. we assume that some fraction of detected infectious individuals progress to the hospitalized class, h(t), where they are unable to pass the disease to the general public; we suppose that some fraction of hospitalized patients ultimately require critical care (and may die) [ ] , but do not explicitly disaggregate, for example, icu and non-icu patients. based on these assumptions and simplifications, the basic model for the transmission dynamics of covid- is given by the following deterministic system of nonlinear differential equations: where is the total population in the community, and β(t) is the baseline infectious contact rate, which is assumed to vary with time in general, but typically taken fixed. additionally, η accounts for the relative infectiousness of asymptomatic carriers (in comparison to symptomatic carriers), σ is the transition rate from the exposed to infectious class (so /σ is the disease incubation period), α is the fraction of cases that are symptomatic, ϕ is the rate at which symptomatic individuals are hospitalized, δ is the disease-induced death rate, and γ a , γ i and γ h are recovery rates for the subscripted population. we suppose hospitalized persons are not exposed to the general population. thus, they are excluded from the tabulation of n , and do not contribute to infection rates in the general community. this general modeling framework is similar to a variety of seir-style models recently employed in [ , ] , for example. for most results in this paper, we use let β(t) ≡ β . however, given ongoing responses to the covid- pandemic in terms of voluntary and mandated social distancing, etc., we also consider the possibility that β varies with time and adopt the following functional form from tang et al. [ ] , with the modification that contact rates do not begin declining from the initial contact rate, β , until time t , where β min is the minimum contact rate and r is the rate at which contact decreases. the incubation period for covid- is estimated to average . days [ ] , similar to other model-based estimates [ ] , giving σ = / . day − . some previous model-based estimates of infectious duration are on the order of several days [ , , ] , with [ ] giving about days for asymptomatic individuals to recover. however, the clinical course of the disease is typically much longer: in a study of hospitalized patients [ ] , average total duration of illness until hospital discharge or death was days, and moreover, the median duration of viral shedding was days in survivors. the effective transmission rate (as a constant), β , ranges from around . to . day − in prior modeling studies [ , , ] , and typically trends down with time [ , ] . we have left this as a free parameter in our fits to washington and new york state mortality data, and find β ≈ . and β ≈ . day − for these states, respectively, values this range. the relative infectiousness of asymptomatic carriers, η, is not known, although ferguson et al. [ ] estimated this parameter at about . , and li et al. [ ] gave values of . - . . the fraction of cases that are symptomatic, α, is also uncertain, with li et al. [ ] suggesting an overall case reporting rate of just % early in the outbreak in china, but increasing to - % later; further, α = / was used in [ ] . in the case of the diamond princess cruise ship [ ] , ( . %) passengers and crews tested positive for sars-cov- , with ( . %) asymptomatic at the time of testing. therefore, we choose α = . as our default. given an average time from symptom onset to dyspnea of days in [ ] , and days to sepsis, a range of - days to hospitalization, a midpoint of days seems reasonable (see also [ ] ); ϕ ≈ . day − is consistent with on the order of - % of symptomatic patients being hospitalized. if about % of hospitalized patients die [ ] , then δ ≈ . day − (based on γ h = / day − ). we assume that some fraction of the general population wears masks with uniform inward efficiency (i.e., primary protection against catching disease) of ϵ i , and outward efficiency (i.e., source control/protection against transmitting disease) of ϵ o . we disaggregate all population variables into those that typically do and do not wear masks, respectively subscripted with u and m . based on the above assumptions and simplifications, the extended multi-group model for covid- (where members of the general public wear masks in public) is given by: all rights reserved. no reuse allowed without permission. the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which was not peer-reviewed) is ( . ) while much more complex than the baseline model, most of the complexity lies in what are essentially bookkeeping terms. we also consider a reduced version of the above model (equations not shown), such that only symptomatically infected persons wear a mask, to compare the consequences of the common recommendation that only those experiencing symptoms (and their immediate caretakers) wear masks with more general population coverage. we assume a roughly linear relationship between the overall filtering efficiency of a mask and clinical efficiency in terms of either inward efficiency (i.e., effect on ϵ i ) or outward efficiency (ϵ o ), based on [ ] . the fit factor for homemade masks averaged in [ ] , while the fit factor averaged for surgical masks. when volunteers coughed into a mask, depending upon sampling method, the number of colony-forming units resulting varied from % to % for homemade masks and - % for surgical masks, relative to no mask [ ] . surgical masks reduced p. aeruginosa infected aerosols produced by coughing by over % in cystic fibrosis patients in [ ] , while surgical masks reduced cfu count by > % in a similar study [ ] . n masks were more effective in both studies. homemade teacloth masks had an inward efficiency between and % over hours of wear in [ ] , while inward efficiency ranged - % and - % for surgical and n -equivalent masks. outward efficiency was marginal for teacloth masks, and about - % for medical masks. surgical masks worn by tuberculosis patients also reduced the infectiousness of hospital ward air in [ ] , and leung et al. [ ] very recently observed surgical masks to decrease infectious aerosol produced by individuals with seasonal coronaviruses. manikin studies seem to recommend masks as especially valuable under coughing conditions for both source control [ ] and prevention [ ] . we therefore estimate that inward mask efficiency could range widely, anywhere from - % for cloth masks, with ≥ % possibly more typical (and higher values are possible for well-made, tightly fitting masks made of optimal materials), - % typical for surgical masks, and > % typical for properly worn n masks. outward mask efficiency could range from practically zero to over % for homemade masks, with % perhaps typical, while surgical masks and n masks are likely - % and - % outwardly protective, respectively. we use state-level time series for cumulative mortality data compiled by center for systems science and engineering at johns hopkins university [ ] , from january , , through april , , to calibrate the model initial conditions and infective contact rate, β , as well as β min when β(t) is taken as an explicit function of time. other parameters are fixed at default values in table . parameter fitting was performed using nonlinear least squares algorithm implemented using the lsqnonlin function in matlab. we consider two us states in particular as case studies, new york and washington, and total population data for each state was defined according to us census data for july , [ ] . closed-form expressions for the basic reproduction number, r , for the baseline model without masks and the full model with masks are given, for β(t) ≡ β , in appendix a and b, respectively. we run simulated epidemics using either β = . or . day − , with other parameters set to the defaults given in table . these parameter sets give epidemic doubling times early in time (in terms of cumulative cases and deaths) of approximately seven or three days, respectively, corresponding to case and mortality doubling times observed (early in time) in washington and new york state, respectively. we use as initial conditions a normalized population of million persons, all of whom are initially susceptible, except initially symptomatically infected (i.e., out , is the initial infection rate), not wearing masks. we choose some fraction of the population to be initially in the masked class ("mask coverage"), which we also denote π, and assume ϵ o = ϵ i = ϵ. the epidemic is allowed to run its course ( simulated months) under constant conditions, and the outcomes of interest are peak hospitalization, cumulative deaths, and total recovered. these results are normalized against the counterfactual of no mask coverage, and results are presented as heat maps in figure . note that the product ϵ × π predicts quite well the effect of mask deployment: figure also shows (relative) peak hospitalizations and cumulative deaths as functions of this product. there is, however, a slight asymmetry between coverage and efficacy, such that increasing coverage of moderately effective masks is generally more useful than increasing the effectiveness of masks from a starting point of moderate coverage. figure : equivalent β ,β (infectious contact rate) under baseline model dynamics as a function of mask coverage × efficacy, with the left panel giving the absolute value, and the right giving the ratio ofβ to the true β in the simulation with masks. that is, simulated epidemics are run with mask coverage and effectiveness ranging from to , and the outcomes are tracked as synthetic data. the baseline model without mask dynamics is then fit to this synthetic data, with β the trainable parameter; the resulting β is theβ . this is done for simulated epidemics with a true β of . , , or . day − . we run the simulated epidemics described, supposing the entire population is unmasked until mass mask adoption after some discrete delay. the level of adoption is also fixed as a constant. we find that a small delay in mask adoption (without any changes in β) has little effect on peak hospitalized fraction or cumulative deaths, but the "point of no return" can rapidly be crossed, if mask adoption is delayed until near the time at which the epidemic otherwise crests. this general pattern holds regardless of β , but the point of no return is further in the future for smaller β . the relationship between mask coverage, efficacy, and metrics of epidemic severity considered above are highly nonlinear. the relationship between β (the infectious contact rate) and such metrics is similarly nonlinear. however, incremental reductions in β , due to social distances measures, etc., can ultimately synergize with other reductions to yield a meaningfully effect on the epidemic. therefore, we numerically determine what the equivalent change in β under the baseline would have been under mask use at different coverage/efficacy levels, and we denote the equivalent β value asβ . that is, we numerically simulate an epidemic with and without masks, with a fixed β . then, we fit the baseline model to this (simulated) case data, yielding a new equivalent β , β . an excellent fit givingβ can almost always be obtained, though occasionally results are extremely sensitive to β for high mask coverage/efficacy, yielding somewhat poorer fits. results all rights reserved. no reuse allowed without permission. the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/ . / . . . doi: medrxiv preprint are summarized in figure , where theβ values obtained and the relative changes in equivalent β (i.e., (β ) / (β )) are plotted as functions of efficacy times coverage, ϵ × π, under simulated epidemics with three baseline (true) β values. from figure , we see that even % coverage with % effective masks roughly halves the effective disease transmission rate. widespread adoption, say % coverage, of masks that are only % effective still reduces the effective transmission rate by about one-third. figure demonstrates the effect of mask coverage on peak hospitalizations, cumulative deaths, and equivalent β values when either ϵ o = . and ϵ i = . , or visa versa (and for simulated epidemics using either β = . or . day − . these results suggest that, all else equal, the protection masks afford against acquiring infection (ϵ o ) is actually slightly more important than protection against transmitting infection (ϵ i ), although there is overall little meaningful asymmetry. finally, we consider numerical experiments where masks are given to all symptomatically infected persons, whether they otherwise habitually wear masks or not (i.e., both i u and i m actually wear masks). we explore how universal mask use in symptomatically infected persons interacts with mask coverage among the general population; we let ϵ i o represent the effectiveness of masks in the symptomatic, not necessarily equal to ϵ o . we again run simulated epidemics with no masks, universal masks among the symptomatic, and then compare different levels of mask coverage in the general (asymptomatic) population. in this section, we use equivalent β as our primary metric. figure shows how this metric varies as a function of the mask effectiveness given to symptomatic persons, along with the coverage and effectiveness of masks worn by the general public. we also explore how conclusions vary when either %, %, or % of infectious covid- patients are asymptomatic (i.e., we vary α). unsurprisingly, the greater the proportion of infected people are asymptomatic, the more benefit there is to giving the general public masks in addition to those experiencing symptoms. fitting to cumulative death data, we use the baseline model to determine the best fixed β and i( ) for cumulative death data for new york and washington state. we use new york state data beginning on march , , through april , , and washington state data from we fix r and t , as it is not possible to uniquely identify r, t and β min , from death or case data alone (see e.g., [ ] on identifiability problems). figure gives cumulative death and case data versus the model predictions for the two states, and for the two choices of β(t). note that while modeled and actual cumulative deaths match well, model-predicted cases markedly exceed reported cases in the data, consistent with the notion of broad underreporting. we then consider either fixed β or time-varying β(t), according to the parameters above, in combination with the following purely hypothetical scenarios in each state. all rights reserved. no reuse allowed without permission. the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which was not peer-reviewed) is . . no masks, epidemic runs its course unaltered with either β(t) ≡ β fixed or β(t) variable as described above. . the two β scenarios are considered in combination with: ( ) weak, moderate, or strong deployment of masks, such that π = . , . , or . ; and ( ) weak, moderate, or strong masks, such that ϵ = . , . , or . . no masks are used up until april , , and then these coverage levels are instantaneously imposed. this yields scenarios in all (nine mask coverage/efficacy scenarios, plus two underlying trends). following the modeled imposition of masks on april , , the scenarios are run for additional simulated days. figures and summarize the future modeled death toll in each city under the different scenarios, along with historical mortality data. figures and show modeled daily death rates, with deaths peaking sometime in late april in new york state under all scenarios, while deaths could peak anywhere from mid-april to later than may, for washington state. we emphasize that these are hypothetical and exploratory results, with possible death tolls varying dramatically based upon the future course of β(t). however, the results do suggest that even modestly effective masks, if widely used, could help "bend the curve," with the relative benefit greater in combination with a lower baseline β or stronger underlying trend towards smaller β(t) (i.e., in washington vs. new york). this study aims to contribute to this debate by providing realistic insight into the communitywide impact of widespread use of face masks by members of the general population. we designed a mathematical model, parameterized using data relevant to covid- transmission dynamics in two us states (new york and washington). the model suggests a nontrivial .... there is considerable ongoing debate on whether to recommend general public face mask use (likely mostly homemade cloth masks or other improvised face coverings) [ ] , and while the situation is in flux, more authorities are recommending public mask use, though they continue to (rightly) cite appreciable uncertainty. with this study, we hope to help inform this debate by providing insight into the potential community-wide impact of widespread face mask use by members of the general population. we have designed a mathematical model, parameterized using data relevant to covid- transmission dynamics in two us states (new york and washington), and our model suggests nontrivial and possibly quite strong benefit to general face mask use. the population-level benefit is greater the earlier masks are adopted, and at least some benefit is realized across a range of epidemic intensities. moreover, even if they have, as a sole intervention, little influence on epidemic outcomes, face masks decrease the equivalent effective transmission rate (β in our model), and thus can stack with other interventions, including social distancing and hygienic measures especially, to ultimately drive nonlinear decreases in epidemic mortality and healthcare system burden. it bears repeating that our model results are consistent with the idea that face masks, while no panacea, may synergize with other non-pharmaceutical control measures and should be used in combination with and not in lieu of these. under simulated epidemics, the effectiveness of face masks in altering the epidemiologic outcomes of peak hospitalization and total deaths is a highly nonlinear function of both mask efficacy and coverage in the population (see figure ) , with the product of mask efficacy and coverage a good one-dimensional surrogate for the effect. we have determined how mask use in the full model alters the equivalent β , denotedβ , under baseline model (without masks), finding this equivalentβ to vary nearly linearly with efficacy × coverage ( figure ). masks alone, unless they are highly effective and nearly universal, may have only a small effect (but still nontrivial, in terms of absolute lives saved) in more severe epidemics, such as the ongoing epidemic in new york state. however, the relative benefit to general masks use may increase with other decreases in β , such that masks can synergize with other public health measures. thus, it is important that masks not be viewed as an alternative, but as a complement, to other public health control measures (including non-pharmaceutical interventions, such as social distancing, self-isolation etc.). delaying mask adoption is also detrimental. these factors together indicate that even in areas or states where the covid- burden is low (e.g. the dakotas), early aggressive action that includes face masks may pay dividends. these general conclusions are illustrated by our simulated case studies, in which we have tuned the infectious contact rate, β (either as fixed β or time-varying β(t)), to cumulative mortality data for washington and new york state through april , , and imposed hypothetical mask adoption scenarios. the estimated range for β is much smaller in washington state, consistent with this state's much slower epidemic growth rate and doubling time. model fitting also suggests that total symptomatic cases may be dramatically undercounted in both areas, consistent with prior conclusions on the pandemic [ ] . simulated futures for both states suggest that broad adoption of even weak masks use could help avoid many deaths, but the greatest relative death reductions are generally seen when the underlying transmission rate also falls or is low at baseline. considering a fixed transmission rate, β , % adoption of %, %, and % effective masks reduces cumulative relative (absolute) mortality by . % ( , ), % ( , ) , and % ( , ), respectively, in new york state. in washington state, relative (absolute) mortality reductions are dramatic, amounting to % ( , ) , % ( , ) , and % ( , ). when β(t) varies with time, new york deaths reductions are % ( , ), % ( , ), and % ( , ), while figures for washington are % ( ), % ( ), and % ( ). in the latter case, the epidemic peaks soon even without masks. thus, a range of outcomes are possible, but both the absolute and relative benefit to weak masks can be quite large; when the relative benefit is small, the absolute benefit in terms of lives is still highly nontrivial. most of our model projected mortality numbers for new york and washington state are quite high (except for variable β(t) in washington), and likely represent worst-case scenarios as they primarily reflect β values early in time. thus, they may be dramatic overestimates, depending upon these states' populations ongoing responses to the covid- epidemics. nevertheless, the estimated transmission values for the two states, under fixed and variable β(t) represent a broad range of possible transmission dynamics, are within the range estimated in prior studies [ , , ] , and so we may have some confidence in our general conclusions on the possible range of benefits to masks. note also that we have restricted our parameter estimation only to initial conditions and transmission parameters, owing to identifiability problems with more complex models and larger parameter groups (see e.g. [ ] ). for example, the same death data may be consistent with either a large β and low δ (death rate), or visa versa. considering the subproblem of general public mask use in addition to mask use for source control by any (known) symptomatic person, we find that general face mask use is still highly beneficial (see figure ) . unsurprisingly, this benefit is greater if a larger proportion of infected people are asymptomatic (i.e., α in the model is smaller). moreover, it is not the case that masks are helpful exclusively when worn by asymptomatic infectious persons for source control, but provide benefit when worn by (genuinely) healthy people for prevention as well. indeed, if there is any asymmetry in outward vs. inward mask effectiveness, inward effectiveness is actually slightly preferred, although the direction of this asymmetry matters little with respect to overall epidemiologic outcomes. at least one experimental study [ ] does suggest that masks may be superior at source control, especially under coughing conditions vs. normal tidal breathing and so any realized benefit of masks in the population may still be more attributable to source control. this is somewhat surprising, given that ϵ o appears more times than ϵ i in the model terms giving the forces of infection, which would suggest outward effectiveness to be of greater import at first glance. our conclusion runs counter to the notion that general public masks are primarily useful in preventing asymptomatically wearers from transmitting disease: masks are valuable as both source control and primary prevention. this may be important to emphasize, as some people who have self-isolated for prolonged periods may reasonably believe that the chance they are asymptomatically infected is very low and therefore do not need a mask if they venture into public, whereas our results indicate they (and the public at large) still stand to benefit. our theoretical results still must be interpreted with caution, owing to a combination of potential high rates of noncompliance with mask use in the community, uncertainty with respect to the intrinsic effectiveness of (especially homemade) masks at blocking respiratory droplets and/or aerosols, and even surprising amounts of uncertainty regarding the basic mechanisms for respiratory infection transmission [ , ] . several lines of evidence support the notion that masks can interfere with respiratory virus transmission, including clinical trials in healthcare workers [ , ] , experimental studies as reviewed [ , , , , ] , and case control data from the sars epidemic [ , ] . given the demonstrated efficacy of medical masks in healthcare workers [ ] , and their likely superiority over cloth masks in [ ] , it is clearly essential that healthcare works be prioritized when it comes to the most effective medical mask supply. fortunately, our theoretical results suggest significant (but potentially highly variable) value even to low quality masks when used widely in the community. with social distancing orders in place, essential service providers (such as retail workers, emergency services, law enforcement, etc.) represent a special category of concern, as they represent a largely unavoidable high contact node in transmission networks: individual publicfacing workers may come into contact with hundreds or thousands of people in the course of a day, in relatively close contact (e.g. cashiers). such contact likely exposes the workers to many asymptomatic carriers, and they may in turn, if asymptomatic, expose many susceptible members of the general public to potential transmission. air exposed to multiple infectious persons (e.g. in grocery stores) could also carry a psuedo-steady load of infectious particles, for which masks would be the only plausible prophylactic [ ] . thus, targeted, highly effective mask use by service workers may be reasonable. we are currently extending the basic model framework presented here to examine this hypothesis. in conclusion, our findings suggest that face mask use should be as nearly universal (i.e., nation-wide) as possible and implemented without delay, even if most mask are homemade and of relatively low quality. this measure could contribute greatly to controlling the covid- pandemic, with the benefit greatest in conjunction with other non-pharmaceutical interventions that reduce community transmission. despite uncertainty, the potential for benefit, the lack of obvious harm, and the precautionary principle lead us to strongly recommend as close to universal (homemade, unless medical masks can be used without diverting healthcare supply) mask use by the general public as possible. the basic reproduction number of the model, denoted by r , is given by . 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respiratory pathogen emissions: potential implications for reducing transmission of covid- & seto, w. h. respiratory virus shedding in exhaled breath and efficacy of face masks modelling the epidemic trend of the novel coronavirus outbreak in china. biorxiv. the baseline model parameters are listed in table , with approximate ranges from the literature based on both clinical and modeling studies novel coronavirus -ncov: early estimation of epidemiological parameters and epidemic predictions uncertainties about the transmission routes of novel coronavirus. influenza and other respiratory viruses why is it difficult to accurately predict the covid- epidemic covid- . github repository annual estimates of the resident population for the united states, regions, states public health responses to covid- outbreaks on cruise ships-worldwide response to covid- in taiwan: big data analytics, new technology, and proactive testing covid- epidemic: disentangling the re-emerging controversy about medical facemasks from an epidemiological perspective on the definition and the computation of the basic reproduction ratio r in models for infectious diseases in heterogeneous populations reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission one of the authors (abg) acknowledge the support, in part, of the simons foundation (award # ) and the national science foundation (award ). all rights reserved. no reuse allowed without permission. the basic reproduction number for both the baseline and the full model is for the special case when β(t) ≡ β . the local stability of the dfe is explored using the next generation operator method [ , ] . using the notation in [ ] , it follows that the matrices f of new infection terms and v of the remaining transfer terms associated with the version of the model are given, respectively, bythe basic reproduction number of the model, denoted by r , is given by the local stability of the dfe is explored using the next generation operator method [ , ] .using the notation in [ ] , it follows that the matrices f of new infection terms and v of the remaining transfer terms associated with the version of the model are given, respectively, by key: cord- -imn g authors: ciminski, kevin; pfaff, florian; beer, martin; schwemmle, martin title: bats reveal the true power of influenza a virus adaptability date: - - journal: plos pathog doi: . /journal.ppat. sha: doc_id: cord_uid: imn g nan influenza a viruses (iavs) circulate among a wide variety of different hosts. they can cross species barriers and establish new virus lineages in avian and mammalian species. as a consequence, iavs are exposed to recurrent selective pressures, leading to a range of virus variants that are able to cope with the new host environment [ ] . bats were not considered to be part of this iav habitat until recently, when two phylogenetically distinct iav lineages, designated h n and h n , were identified in the new world bats sturnira lilium and artibeus spp, respectively [ ] [ ] [ ] . likewise, old world bats can harbor influenza viruses, as exemplified by the genetically distinct h n virus found in egyptian fruit bats (rousettus aegyptiacus) [ ] . the discovery of influenza viruses in new and old world bats did severely challenge our previous conception of iav host range and phylogeny. it, moreover, provided unexpected insights into the remarkable adaptive potential of these viruses and their evolutionary origin. the genetic divergence of iavs circulating in new and old world bat species is much broader than initially anticipated. bat-derived iavs have a higher overall genetic diversity than conventional non-bat iavs [ , ] . internal gene segments that are usually highly conserved among iavs cluster as one narrow clade on a phylogenetic branch when non-bat iavs are analyzed, whereas the corresponding gene segments of new and old world bat iavs form distant outgroups [ , ] (fig a and s fig) . new and old world bat iavs did most likely split into two genetic branches as a result of either geographic separation or multiple early spillover events of ancient viruses. phylogenetic backdating of the internal gene segments suggests that the precursor of the new world bat iavs separated from all other lineages more than years ago, although some uncertainties commonly associated with molecular clock analyses exist (fig b) . interestingly, although the old world bat h n subtype arose from a common ancestor dated around ce (fig b) , its h hemagglutinin (ha) sequence is phylogenetically similar to younger sequences isolated from avian hosts (fig c) . this disparity is best explained by the occurrence of more recent reassortment events between old world bat ancestral viruses and avian strains. furthermore, our phylogenetic analyses reveal that the newly discovered bat iavs share a common ancestor with non-bat iavs (fig a and b) . it is therefore conceivable that all present-day iavs originate from bats. it is equally possible, however, that an even older iav precursor was circulating in avian species and was later introduced into mammals-including bats. what is the biological role of the bat iav surface glycoproteins? iavs initiate infection via the viral ha surface glycoprotein that binds to sialic acid receptors on host cell glycoproteins (fig a) . until recently, it was thought that sialic acids serve as the universal receptors for all influenza virus strains, thereby facilitating cross-species transmission. indeed, the ha of the newly discovered old world bat h n virus binds to α , -sialic in contrast, the internal gene segments of the bat-derived iavs form two outgroups that are located at a more basal position. notably, old world (red) and new world bat iavs (purple) are widely separated. the parallel lines indicate uncertainties between the phylogenetic trees that make up the presented phylogenetic network. (b) a timecalibrated phylogeny was calculated for pb as a representative iav internal gene segment. the timeline (presented in ce) shows that the new world bat iav segments branched off more than years ago (purple node) and that the last common ancestor of old world bat iavs (red node) and conventional iavs (blue node) is around years old. (c) surprisingly, a comparable time-calibrated phylogeny of the old world bat h ha (red node) along with conventional h , h , and h has (blue nodes) points to a much more recent common ancestor for the old world bat-derived ha. see supporting information for a detailed description of the performed phylogenetic analysis (s technical appendix) and a full-sized version of the phylogenetic network (s fig) acid moieties [ ] . surprisingly, however, h and h of the new world bat influenza strains were found to lack this property and cannot use sialic acid receptors for infection [ , , ] . instead, both new world bat-derived ha subtypes utilize major histocompatibility complex class ii (mhc-ii) molecules for cell entry [ , ] . importantly, mhc-ii proteins of multiple species, including chicken, pigs, mice, and humans, can serve as receptors, indicating that receptor usage by bat iavs does not provide a tight species barrier but is compatible with a broad host range ( fig b) [ ] . mhc-ii molecules are normally found on immune cells of the lymphoid tissue, such as b cells, macrophages, and dendritic cells [ ] , but they can also be expressed on epithelial cells [ ] . although mhc-ii molecules are indispensable for h -and h -mediated cell entry [ , ] , it is presently not clear whether they serve as bona fide binding receptors or else as necessary entry cofactors. physical interactions between h /h and mhc-ii molecules need to be demonstrated, and the binding interface(s) need to be defined. conventional iavs and the bat h n virus possess the surface glycoprotein neuraminidase (na), which removes sialic acid residues from infected cells to facilitate the release of newly formed viral particles (fig a) . the new world bat-derived iavs also encode an na protein which, however, has no detectable sialidase activity [ , , , ] . its real function has remained enigmatic until recently. preliminary data now suggest that bat n down-regulates the surface expression of mhc-ii molecules by an as yet unknown mechanism [ ] (fig b) . if confirmed, these data demonstrate that the surface glycoproteins of new world bat iavs have both receptor binding and destroying activities and hence serve the same function as the ha and na proteins of conventional iavs. a well-known characteristic of iavs is their capacity to rapidly evolve and adapt to new environments. their adaptability is based mainly on ( ) gene reassortment (i.e., the ability to exchange gene segments between strains) and ( ) genetic drift that generates a vast number of viral quasispecies due to the infidelity of the viral polymerase [ ] . reassortment between two different yet compatible viruses may generate antigenically novel strains with pandemic potential [ ] . favorable mutations acquired by genetic drift allow evasion from host immune responses and promote successful adaptation to new hosts. for instance, specific amino acid substitutions in ha (e d/g d and q l/g s) enable avian iavs to bind and infect human cells [ ] . interestingly, as the h and h proteins of new world bat iavs are homologs of the ha glycoproteins of conventional iavs, they must have undergone drastic changes to accommodate mhc-ii molecules as entry factors. an exchange of key amino acids in the putative receptor binding site prevents any interaction with sialic acid residues [ , , ] . the underlying selection pressure that resulted in the switch of receptor usage is not known and remains a matter of speculation. a plausible scenario would be that the precursor of the presently known iavs harbored a ha protein with a dual affinity for sialic acids and for an unknown-possibly mhc-ii-related-cellular surface protein, allowing infection of both birds and bats. possibly because of ecological separation of this ancestral influenza virus in new world bats, subsequent evolution in the new host led to increased affinity for mhc-ii. simultaneously, the evolutionary process fostered additional species-specific adaptations. these comprise for example the co-selection of genome packaging signals in conjunction with a specific set (code) of amino acids in the viral nucleoprotein (np) [ ] [ ] [ ] . both the segmentspecific packaging signals and a compatible np amino acid code are compulsory to orchestrate the incorporation of the viral genome into progeny virions [ ] . therefore, because of nonmatching packaging sequences and a different np amino acid code, new world bat and conventional non-bat iavs are unable to reassort their genomes [ ] -an additional unique feature of new world bat iavs, making them a truly divergent entity of iavs. conventional sialic acid-binding ha and na proteins are well studied and known to evolve rapidly in face of a rigorous host immune response [ ] . the surface glycoproteins of the new world bat iavs are still poorly understood and their adaptive potential is presently unknown. first studies show that serial passages of the h n subtype in non-bat epithelial cells resulted in the emergence of efficiently replicating mutant viruses. surprisingly, the selected mutants harbored a truncated nonfunctional n protein yet were able to replicate in mice, ferrets, and bats [ ] (fig c) . sequence analysis showed that these virus variants had acquired at least two mutations in the h head domain that appeared to compensate for the loss of a functional n . perhaps these acquired mutations reduced the binding affinity of h to mhc-ii and supported n -independet replication. virus release may have been further facilitated by the fact that new world bat iav particles bud at the apical membrane of epithelial cells [ ] , where mhc-ii molecules are scarce [ ] . remarkably, h n and h n are the first iav subtypes that utilize a proteinaceous entry receptor. the amazing ability of h to rapidly overcome the absence of a functional n suggests that the structure of h (and possibly h ) may provide a broader scope of evolutionary flexibility than that of conventional sialic acid-dependent iavs. it is therefore tempting to speculate that bat iav ha proteins, and in particular h , might have the potential to adapt to novel and so far unknown entry receptors different from mhc-ii (fig d) . up to now, more than different viruses have been isolated from or detected in bats. some of these bat-borne viruses, such as rabies, ebola, severe acute respiratory syndrome (sars), and middle east respiratory syndrome (mers) virus, have caused human and animal diseases, highlighting their zoonotic and epizootic threat [ ] . the risk for zoonotic transmission and the associated pandemic potential that emanates from an influenza virus considerably depends on its degree of human preadaptation and the ability to overcome host restrictions. whereas avian iavs carry gene segments with species-specific determinants that allow efficient replication in avian but not necessarily human cells [ ] , the new and old world bat iavs appear to possess a human-compatible gene signature due to their mammalian origin. indeed, upon serial passaging of chimeric new world bat iavs in eggs and avian cells, these viruses readily acquired mutations in several genes. in sharp contrast, no such mutations occurred in primary human airway epithelial cell cultures [ ] , indicating that the internal viral proteins are well suited for the replication in human cells. moreover, new world bat iavs might well have the potential to infect humans, because their has can utilize the human mhc-ii homolog human leukocyte antigen-dr isotype (hla-dr) for cell entry [ , ] . nevertheless, h n viruses did not induce any pathogenicity in and were not transmissible among ferrets [ ] , which are considered to be the best animal model for human influenza [ ] . aside from this, h n is also not able to overcome the intracellular restriction imposed by major host defense factors such as the human type i and iii interferon-induced antiviral factor mx (in humans, mxa), because of the lack of mxa escape mutations in np [ ] . as to bat h n , the usage of α , instead of α , -sialic acid residues, together with the lack of obvious mxa resistance mutations in np [ ] , suggests that the old world bat virus possesses a low degree of human preadaptation. thus, based on the currently available data, there is a clear, albeit low, risk for zoonotic spillover of the different bat iavs. in view of their human-adapted internal gene segments and the ability to rapidly acquire new mutations, future transmissions to humans cannot be excluded, and proper surveillance of bat iav distribution is indicated. the presented phylogenetic network is based on the segments pb , pb , pa, np, m, and ns from representative iavs (highlighted in green) and six influenza b viruses (highlighted in yellow). a more detailed close-up zoom of iavs is presented in the main text (fig a) , and methods are described in detail in s technical appendix. iav, influenza a virus; np, nucleoprotein. (tiff) s technical appendix. technical information and methods used for the phylogenetic analysis. (docx) evolutionary processes in influenza viruses: divergence, rapid evolution, and stasis a distinct lineage of influenza a virus from bats new world bats harbor diverse influenza a viruses bat influenza a (hl nl ) virus in fruit bats isolation and characterization of a distinct influenza a virus from egyptian bats bat-derived influenza hemagglutinin h does not bind canonical avian or human receptors and most likely uses a unique entry mechanism hemagglutinin homologue from h n bat influenza virus exhibits divergent receptor-binding and ph-dependent fusion activities entry of the bat influenza h n virus into mammalian cells is enabled by the mhc class ii hla-dr receptor mhc class ii proteins mediate cross-species entry of bat influenza viruses receptor for bat influenza virus uncovers potential risk to humans the ins and outs of mhc class ii-mediated antigen processing and presentation epithelial mhc class ii expression and its role in antigen presentation in the gastrointestinal and respiratory tracts structural and functional characterization of neuraminidase-like molecule n derived from bat influenza a virus crystal structures of two subtype n neuraminidase-like proteins from bat influenza a viruses reveal a diverged putative active site bat influenza viruses transmit among bats but are poorly adapted to non-bat species getting the flu: key facts about influenza virus evolution origins and evolutionary genomics of the swine-origin h n influenza a epidemic host and viral determinants of influenza a virus species specificity a conserved influenza a virus nucleoprotein code controls specific viral genome packaging an infectious batderived chimeric influenza virus harbouring the entry machinery of an influenza a virus the structure of the influenza a virus genome packaging of the influenza virus genome is governed by a plastic network of rna-and nucleoprotein-mediated interactions highly polarized hla class ii antigen processing and presentation by human intestinal epithelial cells synthetically derived bat influenza a-like viruses reveal a cell type-but not species-specific tropism bats and viruses: current research and future trends the ferret: an animal model to study influenza virus human mxa is a potent interspecies barrier for the novel bat-derived influenza a-like virus h n application of phylogenetic networks in evolutionary studies we thank otto haller for critically reading the manuscript and for constructive comments. key: cord- -prl xbnm authors: srivastava, sudhakar; kumar, amit; bauddh, kuldeep; gautam, alok sagar; kumar, sanjeev title: -day lockdown in india dramatically reduced air pollution indices in lucknow and new delhi, india date: - - journal: bull environ contam toxicol doi: . /s - - -w sha: doc_id: cord_uid: prl xbnm in december , the outbreak of viral disease labeled as novel coronavirus started in wuhan, china, which later came to be known as covid- . the disease has spread in almost every part of the world and has been declared a global pandemic in march by world health organization (who). the corona virus outbreak has emerged as one of the deadliest pandemics of all time in human history. the ongoing pandemic of covid- has forced several countries of the world to observe complete lockdown forcing people to live in their homes. india also faced the phase of total lockdown for days (in first phase) to avoid the spread of coronavirus to the maximum possible extent. this lockdown impacted the pollution levels of environment and improved air and water quality in the short span owing to very less human activities. the present work scientifically analyzed the available data for primary air pollutants (pm( . ), no( ), so( ) and co) from two major indian cities, lucknow and new delhi. the analysis was based on air quality data for before lockdown and after lockdown (first phase of days) periods of days each. the results showed significant decline in the studied air pollution indices and demonstrated improvement of air quality in both the cities. the major impact was seen in the levels of pm( . ), no( ) and co. the levels of so( ) showed less significant decline during the lockdown period. the results are presented with future perspectives to mitigate air pollution in near future by adopting the short and periodical lockdown as a tool. electronic supplementary material: the online version of this article ( . /s - - -w) contains supplementary material, which is available to authorized users. since the first case of coronavirus, named as covid- , in wuhan, china , covid- became a pandemic in a short span of time. as on may , ( . am; indian standard time; utc + : ), total , , coronavirus cases and , deaths of coronavirus patients have been reported from countries of the world (who ). india is hugely populated country with a population of . billion as of march, , which is second most in the world (ministry of statistics and programme implementation ). the problem of huge population is worsened by the fact this population lives in a country, which is th largest in the world (shabudeen ) entailing that the density of people residing in per square km area is high. indian cities are hugely populated with new delhi ranking nd most populated city in the world (world urbanization prospects ). further, indian healthcare system is also poor and lacks sophisticated facilities and specialized doctors especially in small towns and villages (ramani and mavalankar ; banerjee et al. ) . india, therefore, lies at huge risk from current pandemic of covid- . as a safety precautionary measure, prime minister of india, shri narendra modi, took an extremely bold decision and declared days complete lockdown in india from midnight of march ( march, - april, . earlier, "janta curfew" (a sort of complete lockdown; maintained by the public for the public; fig s , s ) was performed on nd march, in india. such a lockdown was enforced in china in wuhan, china on rd january, and was lifted on th april, (total days). this lockdown helped china to reduce the number of infections to close to zero. during past months, since coronavirus outbreak began, numerous studies have examined covid- infection. a lot of research on the nature of its spread, the mechanisms of its transfer from human to human, the genome of covid- , the mechanisms of its infection in human cells and its effects on various tissues has been published guo et al. ; baig et al. ; gu et al. ; driggin et al. ) . it is apparent that the lockdown and consequent reduced mobility of people and industrial and almost all other human operations would have also impacted air pollution. in fact, several studies have been published during the last few weeks for europe, china, latin america (he et al. ; ma et al. ; wang et al. ; nakada and urban ) . indian lockdown is first such event locking almost . billion people in their homes and closing down almost all activities in such a large country. in india also, a few studies have shown the positive impact of the lockdown on air and water pollution (sharma et al. ; mahato et al. ; gautam ) .this article scientifically examines the impact of lockdown on air pollution indices in two major cities of india, new delhi and lucknow. new delhi is the capital of india with an area of km and total population of . million. apart from this, seven other cities around new delhi namely noida, ghaziabad, karnal, faridabad, greater noida, meerut and gurgaon make a huge cluster and contribute to human and industrial activities. lucknow is the capital of uttar pradesh with an area of km and total population of . million. both the cities are known to experience severe pollution load days during early winter for the past - years. during november, , the air quality index (aqi) in new delhi and lucknow ranged from - to - , respectively, which was poor (unhealthy) to severe as per national air quality index (naqi ) ( table s ). the present study analyzed air pollution indices for before and after lockdown periods ( days each) for the two cities. our present study used a comprehensive air quality data in two cities of india, lucknow and new delhi. air quality data were collected from fourteen sites viz. central school, gomti nagar, lalbagh and talkatora of lucknow city and anand vihar, bawana, crri mathura road, dwarka-sector , igi airport (t ), du north campus, pusa, rohini, vivek vihar and wazirpur of delhi city (fig. ) . the main concern of the paper was to analyze the trend of concentration of pm . , so , no and co at different sites for before ( / / to / / ) and after lock down ( / / to / / ) periods of days (first phase of lockdown in india). all the data were collected form national air quality index, central pollution control board of india, website (cpcb ). the air quality index (aqi) is defined as ratios of the measured concentration of the atmospheric pollutants to their standard prescribe values (deep et al. ; joshi and mahadev ) . mathematically, the aqi can be evaluated by using following equation for primary pollutants, eq. : the spm . , sso , sno are ambient air quality standards as given by the central pollution control board of india (cpcb) and pm . , so and no represent the actual observational values of pollutants (punith and nagarajappa ) . the aqi was calculated by using mass concentration of these three primary pollutants (pm . , so and no ) for all specified locations. the high aqi values represent a higher level of atmospheric pollutants at the monitoring site. according to deep et al. ( ) ; guttikunda et al. ( ) and naqi ( ), the aqi scale can be divided into six different categories as per the range and associated health impacts (table s ) . to understand the influence of long-range transportation of atmospheric pollutants at both monitoring zones, the air mass back trajectory analysis was also performed. the air mass back trajectory was extracted from national oceanic and atmospheric administration (noaa) air resources laboratory (arl) hybrid single-particle lagrangian integrated trajectory (hysplit) model (stein et al. ) . the days air mass back trajectories were calculated for local time : at the elevation of m from mean sea levels (he et al. ; rozwadowska et al. ) for both cities. the data of air quality parameters i.e. pm . , no , so and co were taken for four locations of lucknow and ten locations of new delhi for before lockdown ( / / to / / ) and after lockdown ( / / to / / ) periods (tables s a, b). the level of pm . varied from avg - μg/m in four locations of lucknow before lockdown. on th march, , pm . level was the lowest μg/m at gomti nagar and highest μg/m at talkatora. on th march , pm . levels declined to and μg/m , respectively in these areas while to and μg/ m , respectively on th april, (fig. a) . in new delhi, the pm . level ranged from to μg/m during before lockdown period in different locations. on th march, the range of pm . was to μg/m and on th april, , it was to μg/m (fig. a) . the range of no before and after lockdown period in lucknow was - μg/m and - μg/m , respectively denoting a significant decline (fig. b) . in new delhi also, before and after lockdown levels of no were significantly different. before lockdown, no ranged from to μg/ m while after lockdown, it ranged from to μg/m . the low value of μg/m in new delhi before lockdown was from indira gandhi international airport terminal- ( fig. b) . thus, even before lockdown, some highly maintained and clean areas had low pollution levels. the levels of so , however, did not show much change before and after lockdown in both lucknow and new delhi (figs. c, c) . the level of co showed decline from - μg/m to - μg/m in lucknow while from - μg/m to - μg/m in new delhi (figs. d, d) . the average and median (fig s ) values of all these four parameters were also calculated for both the cities for before and after lockdown period ( days befor lock down after lock down avg co fig. a-d the effects of lockdown before and after pm . , no , so and co level at lucknow and delhi city average value of pm . was . μg/m (gomti nagar) and . μg/m (gomti nagar) before and after lockdown, respectively in lucknow. for new delhi, the minimum average values of pm . were . μg/m (north campus, du) and . μg/m (north campus, du) before and after lockdown, respectively. in case of no the average value was . μg/m (before) and . μg/m (after) in central school, lucknow and . μg/m (north campus du) and . μg/m (igi airport) in new delhi before and after lockdown, respectively. the minimum average value of so was found to be . μg/m (central school) and . μg/m (talkatora) in lucknow before and after lockdown, respectively. the values of so were . μg/m (anand vihar) and . μg/m (pusa) in new delhi before and after lockdown, respectively. in case of co, the minimum average value was . μg/m (gomati nagar) and μg/m (gomti nagar) in lucknow and . μg/m (pusa) and . μg/m (bawana) in new delhi before and after lockdown, respectively. these days average values of all four major air contaminants for before and after lockdown periods clearly indicate the significant reduction in the concentration of primary air pollutants. hence, the trend analysis depicted a decline in air pollution indices in both the cities. however, some areas, like residential colonies, airport terminals and official localities, where the cleanliness is maintained in much better way and vehicular load is less, the pollution was found to be low even during normal phase. hence, the minimum levels do not clearly indicate the extent of decline in overall pollution across the city during lockdown phase. pm . are submicron size particles, which affect health of people through congestion in lungs (ma et al. ; li et al. ) . no , so and co affects human health severely and cause respiratory tract illness, asthma exacerbations and decreased lung function etc. (harre et al. ; oguntoke and yussuf ) . however, even after the decline, the level of pm . remained higher than who recommended level of μg/m for the annual mean (who ) . same is true for other parameters, whose who safe limits are µg/m (no ), µg/ m (so ) and µg/m (co) for the annual mean nonetheless, such a significant decline in air quality is supposed to lead to improved health of people and avoid air pollution linked health problems and even deaths. he et al. ( ) in a similar study on lockdown induced air pollution effects in china indicated that improvement in air quality might avoid , to , premature deaths on a monthly basis. however, they suggested that if indoor air quality becomes toxic during lockdown, it might reduce the presumed benefits (he et al. ) . the exact benefits of current air pollution decline would come to knowledge in due course of time. presently, however, it is well clear that reduced human activities have created a much clear and clean air. the aqi was also calculated for locations for before and after lockdown in two cities (fig. ) . the aqi of lucknow was found to be in the range of . to . and remained in the unhealthy moderately polluted to poor range (aqi between and ) as described in the naqi (table s ). after the implication of lockdown, the aqi was significantly changed and was found to be in the range of . to . which falls in good ( - at central school fig. air quality index in lucknow and delhi city (before and after lockdown). aqi were calculated using pm . , so and no and gomti nagar) to satisfactory ( - lalbagh and talkatora) aqi range. in new delhi, the aqi was found to be poor at bawana, crri mathura road and dwarka-sector , as well as at some other monitoring site such as anand vihar, igi airport (t ), north campus delhi university (du), pusa, rohini, vivekvihar and wazipur with the values ( - ) being in moderately polluted to poor aqi range ( to ) before the implication of lockdown. however, a dramatic reduction was observed in the aqi at all ten monitoring sites over delhi with aqi range of . to . after lockdown. thus, aqi values after lockdown fell in the range of good to satisfactory. the drastic change observed aqi values were mainly due to cut down in local anthropogenic emission sources such as industrial units, vehicular movements, transportation, and construction work, etc. to understand the influence of long-range transportation of atmospheric pollutants at both monitoring zones, the air mass back trajectory analysis was also performed. air mass trajectories for four locations in lucknow and ten locations in delhi were very close to each other and so locations were considered as a single location in both cities. the mass concentration of pm . , so , no and co showed significant fluctuation during before lockdown and after lockdown periods (fig. a, b) . the air mass travelled from european, african, and gulf countries as well afghanistan, tajikistan, western pakistan via rajasthan, punjab to delhi and then to lucknow during both events. however, few trajectories also originated from the arabian sea and the gujrat state of india in case of lucknow. in new delhi, significant contribution was also noticed from local emission entities located in national capital region (ncr). so the air quality in both cities was dominantly influenced by long-range transportation, which also contributed to variation in the pollutant load. air back mass trajectory has been well documented and examined by tiwari et al. ( ) and yerramsetti et al. ( ) for ambient air of delhi and lucknow, respectively. in conclusion, results of the present study indicate a sharp decline in overall air quality indexes and in the concentration of primary air pollutants. the study needs to be extended to analysis of secondary air pollutants, such as ozone, also. however, such a lockdown cannot be planned in normal conditions in such a huge country and therefore it cannot be considered as a permanent solution. nevertheless, taking lessons from the present lockdown and emerging and foreseen environmental scenarios, we propose following prospective measures that can be adopted in future to mitigate air pollution. . in every to months, a short to days complete/partial lockdown can be practiced to mitigate environmental pollution especially air pollution. during such a lockdown, people should be encouraged to have regular walk and jogging in nearby areas without vehicular use. in this way, people would not only avoid continuous indoor air and mental stress of lockdown but would also enjoy outside clean air. . weekly or fortnightly, one "no vehicle day" can be practiced. evidence of the covid- virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms putting a band-aid on a corpse: incentives for nurses in the indian public health care system central pollution control board clinical characteristics and intrauterine vertical transmission potential of covid- infection in nine pregnant women: a retrospective review of medical records evaluation of ambient air quality in dehradun city during - cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease (covid- ) pandemic the influence of covid- on air quality in india: a boon or inutile covid- : gastrointestinal manifestations and potential fecal-oral transmission the origin, transmission and clinical therapies on coronavirus disease (covid- ) outbreak-an update on the status air 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implementation, govt. of india covid- pandemic: impacts on the air quality during the partial lockdown in são paulo state central pollution control board (ministry of environment, forests & climate change) air pollution arising from vehicular emissions and the associated human health problems in abeokuta metropolis nigeria monitoring of spm, so , no , and air quality index in selected areas of davangere city during summer season health system in india: opportunities and challenges for improvements cluster analysis of the impact of air back-trajectories on aerosol optical properties at hornsund spitsbergen impact upon the indian socio-economic fronts by climate change effect of restricted emissions during covid- on air quality in india hysplit atmospheric transport and dispersion modeling system assessment of pm and pm over guwahati in brahmaputra river valley: temporal evolution, source apportionment and meteorological dependence severe air pollution events not avoided by reduced anthropogenic activities during covid- outbreak air quality guidelines for particulate matter, ozone, nitrogen dioxide and sulfur dioxide: global update : summary of risk assessment world health organization ( ) coronavirus disease (covid- ) situation reports. world health organization population division the impact assessment of diwali fireworks emissions on the air quality of a tropical urban site a novel coronavirus from patients with pneumonia in china the authors declare that they have no conflict of interest. key: cord- -y xpvwol authors: bayne, karen; wreford, anita; edwards, peter; renwick, alan title: towards a bioeconomic vision for new zealand – unlocking barriers to enable new pathways and trajectories date: - - journal: n biotechnol doi: . /j.nbt. . . sha: doc_id: cord_uid: y xpvwol there has been significant national interest and movement towards bioeconomic policy over the past decade. through an examination of the current bioeconomic pathways in new zealand, this paper outlines key barriers that transition pathways will need to overcome and factors needing development within the country’s bioeconomic environment. new zealand’s strength in primary production, coupled with a market-led economy and recent green growth with low carbon policies, provide an excellent platform for bioeconomic development. however, the strength in established biological industries and lack of clearly defined vision or cohesive support for bioeconomic development provide sufficient inertia to realising the full potential. for a bioeconomy in new zealand to flourish, a primary sector model that is cohesive and more integrated is needed to develop new niche industries and attract finance, while providing an overarching governance system to the primary industries. new zealand has long had an economy based on the primary industries -farming, forestry and food production. these have commonly been based on primary products as commodities, with new zealand seen as a key commodity exporting economy in asia-pacific [ ] . while many new zealand energy and growth strategies hint at production via a bioeconomy [ , ] , it has only been during the covid- pandemic that a bioeconomy roadmap or strategy has emerged, primarily to accelerate recovery [ ] . this new national strategy formalises new zealand's potential to capitalise on its strength in natural resources, and existing strong research and development in the primary sector focussed on innovation for national wealth gain. however, it does appear to remain agri-dominant, constraining opportunities for inter-sectoral innovation and a wider application of biotechnology investment. by , the new national strategy seeks to add $us b in export earnings, reduce biogenic methane % below levels, and grow employment in the primary sector by % [ ] . new zealand economic policy since the mid- s has been market-led, with limited government intervention in the primary sector markets [ ] . a heavily siloed agricultural economy has resulted with each primary sector operating in an insular manner and a duplication of efforts within research and development (r&d), trade policy and export marketing across the sectors [ ] . as the population expands, meeting the government's growth targets [ ] in a sustainable manner will require a shift in thinking that allows for adding value to natural resources while also reducing environmental degradation and maintaining social licence to operate. it may appear that new zealand has a pre-existing dominance in biological industries, particularly in food and fibre, a well-established export economy, and therefore little capacity or need to increase and improve on building a flourishing bioeconomy. such thinking ignores the fact that the current new zealand primary-sector economy has several major limitations impeding the emergence of a bioeconomy, including its pre-existing dominance. this paper explores these limitations to the present 'old' bioeconomic production model currently operating in new zealand, and discusses potential for transformation within the new zealand primary production system. first, the paper provides a review of the visions and drivers of international bioeconomies and the current status of the bioeconomy in new zealand. following this the pathway and trajectories being taken to support a 'new' bioeconomy in new zealand are examined, before identifying the main barriers to a more widespread adoption of this integrated bioeconomic approach. strategies for overcoming these barriers to enable a flourishing bioeconomy are then discussed. biotechnology has been a critical driver in the ability to transform biological resources for enhanced economic wealth and societal benefit [ ] . the biotech 'revolution' reached a scale by which a new term, bioeconomy, was coined to encompass the wealth contribution being created from biotechnology -in biotechnology contributed $us b to the us economy [ , ] . the oecd heavily reference biotechnology in the development and growth of a bioeconomic future [ ] . in particular, biotechnological processes (including bioenergy, chemical and industrial biotech processes) have enabled higher value extraction from a range of biomass inputs across the primary sector, allowing conversion to critical components of the bioeconomy -biofuels, bioproducts and advanced food and fibre production [ ] . some proponents of a bioeconomy cite this ability to capitalise on biotech advancements using biological systems (e.g. [ , , ] ), but the bioeconomy has come to mean much more than biotechnology. today, the bioeconomy is promoted variously as a means to create wealth, address a multitude of environmental pressures through the reduction and re-integration of waste streams (circular economy), generate new value from waste, enable a low carbon economy, design and develop production and processing facilities and entirely new integrated and resilient industries and create myriad economic opportunities through biological science [ ] . in a global strategy review, seven key drivers have been identified [ ] : . waste reduction and circularity. . health improvements to reduce poverty levels, improve life expectancy and reduce infant mortality. . addressing climate change by reduction in greenhouse gas (ghg) emissions perspectives on the bioeconomy have shifted over time, beginning with an initial focus on biotechnology and green growth, before moving into a bio-resource focus and inclusion of environmental objectives, in particular resource substitution surrounding 'peak oil' in the first decade of this century. over the past decade a 'biotech innovation' phase saw the rise of life sciences for commercial and industrial growth and is now being driven by a dichotomous evolution towards both circular bioeconomies that include cascading and the interlinkage of different biomass value chains, with an 'agroecological' emphasis on sufficiency and socio-political transition to achieve the same ( [ , ] . three main 'visions' which various global strategies appear to be following have been outlined [ ] . first, the bioeconomy as a means to create jobs and economic wealth through the application of biotechnology and commercialisation of biobased r&d. this 'biotechnology' vision led to science clusters and was mainly taken up by mainstream science fields. the second 'bioresource' vision expands on economic growth, but through a sustainability lens, and is usually achieved through the conversion and improvement in processing of bioresources. the bioeconomy is usually promoted in order to optimise land use, particularly in the establishment of marginal lands in biofuels production, and in increasing the volumes of bioresources and including bioresources to reduce waste flows. a consideration in this vision is the ability to enhance the rural sectors through sustainable regional development in agriculture. these first two visions have an engineering and natural sciences perspective and may be complementary to some extent [ ] . in comparison, the 'bio-ecology' vision is more concerned with environmental conservation and maintenance, particularly sustained ecological viability and avoidance of degraded ecosystems, such as soils and water systems. this third vision takes a more integrated production and value-added approach, ensuring not only circularity, but ecological and social sustainability within production. in this vision the focus is moving towards impacts of bioeconomic policy and vision on society, and will require socio-political trajectories and socio-technical development to enable appropriate transition paths [ , ] . the main boundaries of the bioeconomy were outlined in [ ] . they include activities leading to:  lowered ghg emissions;  and/or reducing waste or incorporating renewable or recyclable materials;  and/or processes which look to cascade value throughout the chain and extract higher value downstream from wastes;  and/or new products that utilise the functional benefits that biological resources alone provide and that are not linked to waste reduction or fossil fuel substitution. four main bioeconomic pathway paradigms were outlined [ ] that emerge from the intersection of visions (on an industrial biotechnology -agroecology continuum) with drivers (capitalist growth -lowproduction sufficiency continuum) (figure ). new zealand has , km land mass and a small population base. this equates to . ha of land resource per capita, relatively generous at global scale. it has significantly higher pasturelands than the oecd average ( % versus %) and a higher forest cover ( % versus %), but lower arable cropping than oecd average (just % compared to %). new zealand productive land use is dominated by pastoral farming, particularly dairy farming ( % of agricultural operating income), followed by sheep and beef farming. along with direct export earnings, the primary sectors are also fundamental to employment, particularly in the regions, and in the science sector [ ] . new zealand has been reducing reliance on coal and natural gas but relies heavily on imports of fossil fuel for transportation energy. % of the pj (petajoules) total primary energy supply consumed annually is in fossil fuels [ ] . in contrast, new zealand generates pj of renewable energy, with the majority ( %) from geothermal sources and % from hydropower, % bioenergy and % wind. fifty-eight of the pj of bioenergy is in the form of biomass, usually combustion of sawmilling and pulp and paper residues [ ] . biotechnology contributes to the national economy, mainly through advances in industrial processing and genetics. the last national biotechnology survey was conducted in [ ] where bioscience then contributed $us m to gross domestic product (gdp). biotechnz, a member-funded association created by the new zealand technology industry association incorporated to support the national biotechnology community, is currently surveying new zealand biotechnology firms to establish their contribution to the economy as well as identifying opportunities to contribute to further economic growth [ ] . new zealand's gdp contribution from the current bioeconomy is estimated at %, or $us b, with % from food, % from forestry, % from construction (mostly housing), % from support services, and % from wastewater treatment [ ] . based on the available resources, new zealand's primary sectors will still be predominant players in any transition to a 'new' bioeconomy, and have an important influence globally through exports, as nearly half our $us . billion export revenues are from the primary industries [ ] . however, outside of agritech, biotechnology will likely have an increasing role to play in the growth of our bioeconomy in a post-covid environment for advancing healthcare and chemical processing technologies using molecular biology [ ] . the analysis in this paper is a mixed methods approach, based primarily on a review of relevant literature, complemented by a survey of participants at a national symposium in april . articles reflecting the current bioeconomy discourse and literature on innovation and transformation were sought using research databases (e.g. scopus, worldcat etc.) with an emphasis towards selecting bioeconomy and transition review articles, or those articles where national bioeconomy and biotechnology strategies were discussed. in addition to this scientific literature, international and regional policy strategies were reviewed, including relevant nz policy documents. international literature concerning bioeconomic strategies, divergent visions of the bioeconomy, and current concepts concerning bioeconomic pathways and policy development (both international and within new zealand) was examined. international approaches were concurrently assessed against the current new zealand approach to bioeconomic development, primarily from grey literature, which complemented the data gathered through the survey. the survey involved distribution of paper surveys to approximately participants prior to a presentation by one of the authors on the topic of the bioeconomy. questions were developed based on literature, particularly [ ] . respondents were questioned on their familiarity with and expectations around the concept of the bioeconomy in a nz context. forty-seven completed, useable surveys were returned. a descriptive analysis of the results was undertaken and is summarised in the next section. the data from the survey and grey literature was assessed against current drivers and visions as espoused by [ ] and [ ] , and against the pathway quadrants developed by [ ] , to provide some insight into the current new zealand approach to a bioeconomy. finally, the strengths and weaknesses in new zealand's bioeconomy, as outlined by [ ] , were cross-examined against the current trajectories using swot analysis and a causal framework investigating drivers, barriers and enablers. in new zealand, the current definition of a bioeconomy is "the set of economic activities relating to the invention, development, production and use of biological products and processes " p. [ ] . this definition is fairly broad in nature, though it is missing many of the more social and environmental elements that are required for a fully functioning bioeconomy. this relates strongly to the more linear biotechnology or bio-resource vision than the interactive or circular bioecology visions outlined by [ ] . in [ ] , the area highlighted is that "new zealand arguably already has a 'bioeconomy' in the literal sense of the term, as much of the economy is based on the primary sector" p (just over half of export earnings [ ] ). figure , adapted from [ ] , indicates the different outputs and impacts between the existing 'old' bioeconomy within new zealand, and the emerging 'new' bioeconomy. two main drivers are behind new zealand's bioeconomic transformation: developing higher value biobased products or biological inputs to create economic value and improving sustainability through mitigating environmental issues (waste, pollution, energy use and ghg emissions). surveyed stakeholder respondents were most familiar with the term 'bioeconomy' in the context of bioenergy ( %), and food production ( %). fewer than half were familiar with the bioeconomy in the context of biotechnology ( %), % were familiar in the context of innovative products from primary production, and % were not familiar with the term at all. using categories derived from [ ] , respondents ranked these categories (figure ) with = most important and = least important. the highest ranked potential benefit was a shift from fossil fuels and associated environmental effects ( . ), followed closely by higher value products ( . ) and a resource-efficient society ( . ). ranking slightly lower in terms of priorities was less waste to landfill ( . ) and improved health and nutrition ( . ). further down in priority was energy security ( . ) and lowest ranked of all was job creation ( . ). it is worth noting the high-ranking that a shift from fossil fuels received, as the current developments in the bioeconomy in new zealand do not place particular emphasis on this benefit. higher value products followed closely behind in the survey, which is where most of the focus is currently in new zealand. although historically bio-resource centred in outlook, recent interest in creating a circular bioeconomy has emerged that addresses primary sector waste, and commitments to reduced ghg emissions (the low carbon economy), while maintaining economic growth ( [ ] [ ] [ ] ). these include a recognition of the opportunities available through high-value forest-based residues ( [ , ] ) and lowering of carbon emissions [ ] . overall (as stated in [ ] ), the scan of current activity within new zealand's emerging bioeconomy shows the following bioeconomic pathways [ ] : the bioeconomy pathways, when mapped against the framework in [ ] , show that the transition is still largely driven by capitalist growth rather than sufficiency trajectories, but is split between the development in new agro-ecological industries and a focus on industrial biotech (figure ) . new zealand has yet to move fully into an 'eco-retreat' driven pathway that addresses the current social concerns of agricultural expansion coming from the non-producer side of the debate. while these individual pathways show promise, they are unlikely to lead to the full realisation of the 'new' bioeconomic direction in the presence of several barriers, discussed below. by assessing the new zealand bioeconomy against a set of six structural elements (renewable resources; knowledge, innovation & technology; finance and governance; research & development; private and public expectations; processes, products & services) strengths and weaknesses present in enabling bioeconomic transformation have been highlighted [ ] . an examination of new zealand's current bioeconomic system against the 'new' bioeconomy vision and pathways shows several barriers to transitional pathways present in the primary-sector system that might hamper bioeconomic development reaching its full potential, due to the following weaknesses. first, the returns from agricultural production are low compared to international profits ([ ] [ ] ); secondly, the environmental cost of production is reaching a point by which it is clear that changes to the current intensification norm are needed [ ] ; thirdly, new zealand's siloed primary sector economy and market dominance of large well-established corporates provides inertia to sectoral transformation; fourthly, some recent efforts to build and grow the bioeconomy have been met with social and market resistance; and finally, new zealand is currently lacking governance and financial enablers to provide effective transition [ ] . the real contribution of agriculture, forestry and fisheries to the national gdp has dropped from around - % in the s to - % during - [ ] , though accounting for agricultural additionalities it has been estimated at closer to % gdp contribution [ ] . returns from primary production are still much lower than their real market value, due to three core factors. first, the majority of new zealand's primary production is in commodity goods, used as 'feedstocks' into other sectors, and into international markets for secondary processing. new zealand has lower than optimal manufacturing and processing sectors in which to turn these goods into higher value products but lower labour costs relative to many other industrialised nations [ ] . secondly, market value is lost due to competition both within and between industries and sectors. collaboration in terms of joint marketing for export access, joint transportation, port and warehouse storage, shipping and inventory assessment could benefit new zealand producers from the same regions, or having similar supply chain partners. thirdly, some commentators note that there is increased revenue to be made through capitalising further on the unique attributes that provenance and cultural heritage provide, even for commodity goods [ ] . as a result, the primary sector goods sold in international markets for $us b earn the new zealand economy just $us b, meaning the nation loses out on % of the real value of our largest sectoral exports [ ] . the "sustainable intensification" [ ] route followed by new zealand primary production is now in question, as the country experiences unprecedented levels of polluted waterways [ ] and very little reduction in ghg emissions [ ] . a radical reduction in new zealand's dairy cattle numbers is required to reach climate change obligations [ ] , in conjunction with increased tree planting [ ] . recommendations from the oecd are for new zealand to develop a long-term vision for a transition towards a low-carbon, greener economy. however, the new zealand government currently promotes a 'green growth' strategy [ ] , aimed at substantially increasing export revenues, thus retaining a capitalist growth over sufficiency model. attaining the higher export revenues without significant increases in environmental costs requires higher value production. higher value production, or ensuring our lost export value moves back up the supply chain to producers' pockets, will need a crosssectoral viewpoint, alongside new sector emergence from a multi-sector and multi-actor innovation system that supports and aids the bioeconomic transition path. new zealand's primary sectors operate independently of one another, which is not conducive to the principle of circular economy and the sort of supply chain integration needed for biorefinery inputs, which often draw from multiple feedstock sources. although at the national level the ministry of primary industries provides overarching policy, both sectoral governance and producer bodies are structured to enable independent production and thinking. for example, multiple producer bodies exist for each major sector: horticulture (zespri), agriculture (beef+lamb; dairynz), fisheries (seafoodnz) and forestry (woodco). this is also evident from the prevalence of sectoral-based activities, in terms of field days, seminars, pro-sector initiatives and member associations, from within r&d itself to industry organisations and farmers themselves. bioeconomy initiatives also tend to be promoted as sectoral growth strategies, such as the wood processing strategy, and aquaculture strategy. these look to enhance economic returns to a single sector, rather than creating a crosscutting bioeconomy allowing for multiple feedstocks and a range of high value outputs through a regional strategy for industrial biofinery. more recently, calls for a national strategy on sustainable j o u r n a l p r e -p r o o f food production have emerged , but again this lacks integration with other bioeconomic sectors such as biofuels and biofibre production [ ] . one cannot assume that 'all things bio-based' will naturally result in improved sustainable development goal (sdg) outcomes, as evidence shows that the bioeconomy cannot be considered as self-evidently sustainable [ ] . if done well, it will provide goods and resources for an ever-increasing population, while reducing the amount of carbon emissions and enabling developing nations to participate in greater economic wealth generation. poorly designed bioeconomic transition that requires an immense volume of biomass demand could result in harmful impacts such as biodiversity and soil loss, competition over land use, and escalation of hunger and resource conflict [ , ] . european bioeconomy strategies now acknowledge that a biobased economy can only be sustainable through a concurrent socio-ecological transformation [ , ] . in new zealand, the aquaculture sector has shown significant potential, and an aquaculture strategy has been released aiming for a quadrupling in value of the industry by [ ] . however, public resistance to aquaculture due to rapid growth has been an issue for over a decade [ ] . more recently, public resistance to salmon farms in the marlborough sounds has resulted in legal challenges, with only four of nine farms being approved [ ] . resistance and public concerns surround the impact on local residents from a change in visual ocean vista, night lighting, the perceived fouling of waterways and introduced species [ , ] . presently, new zealand takes a precautionary principle to use of new technology [ ] . acceptance of genetic modification (gm) could radically enhance a bioeconomy in new zealand, but social support appears to differ depending on how gm is implemented ( [ , ] ), and the economic benefits remain uncertain [ ] . more recently, it was found that public acceptance of gm for controlling invasive species was still contentious and highly variable and depended on the context in which it might be introduced [ ] . public concern regarding the 'neo-liberalisation of nature' and 'biocapitalism' through extension of market forces to biological resources ( [ , ] ) as well as ownership, equity and capture of indigenous knowledge, requires deliberation when creating bioeconomic value. in the early s, there was much interest and growth within the new zealand science environment towards biotechnology, and a national biotechnology strategy emerged in [ ] . the formation of nzbio as a networking and connecting private sector organisation to debate and enhance issues of biotechnology for new zealand further advanced the nation's biotechnology sector. in , the new zealand bioenergy strategy was released [ ], with strong support from the forestry and wood processing sectors of new zealand. while incorporated in some international bioeconomic reviews (e.g. [ ] ) as a national bioeconomy strategy, this was developed independently outside of government by the bioenergy association of new zealand (banz) and nzbio. the new zealand bioenergy strategy sought to deliver substantial economic growth and employment, but also noted the need for collaborative industry vision, and strong government leadership in order to achieve the primary goals: supplying % of the country's energy need and % of the country's transport fuels by , through leveraging the capacity and expertise in the forestry and wood processing sectors [ ] . globally, biofuels consumption between - is anticipated to increase in both bioethanol (by b litres) and biodiesel (by b litres) [ ] . following the heightened interest at the start of the century, the optimism and momentum around biotechnology for new zealand has waned, though biotechnz retains a vision for new zealand to "maximise nz bioscience and technology capability to create a strong nz bioeconomy" [ ] . today, new zealand no longer has a national biotechnology strategy, though nzbiotech states that this is "vital" [ ] . the failure of some new zealand biotechnology start-ups is also attributed to lack of investment, both private and public (e.g. protemix, icp), where the size of the investment market in new zealand makes economies of scale to commercialise biotechnology more difficult [ ] [ ] . biotechnology leaders advocate an environmental application for its growth in new zealand over health and medical applications, leveraging strong biomass resources and agritech science [ ] . the first indications of government policy since towards creating a bioeconomy only emerged in with the primary sector science roadmap [ ] where the bioeconomy is specifically referred to, with the sub-title "strengthening new zealand's bioeconomy for future generations". more recently, the new zealand energy efficiency and conservation strategy - (nzeecs) [ ] has sought to establish an energy productive, low emissions economy, mainly through enhancing production of renewables and reducing reliance on fossil fuels, particularly in transportation (through increased electric vehicle fleet) and electricity supply (a target of % renewable electricity production by ) [ ] . most recently, (july ), the new zealand government released "fit for a better world" as a post-covid recovery strategy encompassing principles of te taio (respect for the natural world), zero carbon and quality food and fibre products [ ] . this bioeconomy strategy sees the primary sector as the foundation of new zealand's economic recovery, and envisions "providing the world's most discerning consumers with outstanding, ethically-produced food, natural fibres, drinks, co-and bioproducts, all sourced from our land and oceans" p. [ ] both finance and governance were identified [ ] as critical elements that are currently not fully present in the new zealand bioeconomic system, and that hamper a high-value bioeconomy from being fully realised. though the strategy and vision now promote a fully integrated bioeconomic pathway to be realised, the supporting governance and financial structures to implement and realise the national vision remain critical. overcoming the barriers identified in the previous section is essential for new zealand to achieve its potential in this area, while leveraging off the strength of our primary sectors. in returning to the strengths previously identified [ ] , and nascent developing pathways, four factors may facilitate a sustainable pathway to a genuine bioeconomy: . allowing room for a greater number of smallerscale operators; . enabling markets for higher-value bio-based producers; . ensuring continuity for the established mainstream; and . increasing adaptability and flexibility within the various bio-based sectors to allow cross fertilisation to occur. for a bioeconomy to develop, new zealand needs to conquer the question of how to be viable with smaller scale. while consolidation provides efficiencies and economies of scale in commodity production, smaller scale enterprises will likely be in specialised production and niche markets. remote rural communities require some form of enterprise and small scale, distributed production that supports a circular bioeconomy could achieve the drivers for greener economic growth, as well as job creation and regional development. smaller scale producers will, however, need to leverage the capability built from within the mainstream players, particularly in terms of r&d capacity, integration into the larger sectoral supply chains, and infrastructural investment. for smaller-scale operators to thrive, they will require entry into global markets. the global marketplace rewards producers that can connect with consumers on an individual and experiential level. many smaller enterprises will require a range of global supply chain partnerships that can build and deliver higher-value production and provide differentiated marketing solutions to ensure wealth from consumers reaches the original producers. quality niche production of goods that meet conditions sought after by international markets have been realised by a small number of producers, some of which (e.g. comvita, winenz, merinonz) have moved from niche production into mainstream agricultural export-revenue production. not all production will need to transition immediately to a 'new' bioeconomic business model, and in ensuring growth for the smaller-scale and higher value niche producers, any bioeconomy strategy must also provide stable continuity and transition time for the existing cash cow. there is large momentum in the existing new zealand bioeconomic system, with many producers both wanting to transition to a more sustainable and higher-value production model, but fearing the transitional loss of power-base and authority that their sector, business model or enterprise currently has. high capital investment for niche production may only be available from within existing large corporate agricultural entities, who can aid transition. more established sectors have a role to play in niche industry support by linking with them, as well as enabling boundary expansion within their larger sectors to enable new thinking and potential development paths. niches in turn can assist the established sectors to transition by providing opportunities for diversity and innovation. . increasing adaptability and flexibility within the various bio-based sectors to allow cross fertilisation to occur. breaking down the heavily siloed structural system within the primary sector is essential to enabling circularity and a production system that can handle multiple input feedstocks, cross-sectoral actors and a regional biorefinery approach to distribution and marketing of multiple biological outputsfood, fuels (energy and power), as well as value-added biomaterials and biochemicals from biomass [ ] . at the larger scale, separate entities could come together in an industrial collective involving physical exchange of materials, energy, water, and/or by-products. in a fully-functioning bioeconomy, regionally distributed processing and manufacturing through smaller and more agile clusters might displace the current centralised hubs that support regional but specialised production, processing and manufacturing infrastructure, but might fail without high-level vision and pathway support. enacting cross-sectoral pathways and integration within stakeholder processes, as called upon by [ ] is now urgently required. it is likely that radical changes in food production and fibre processing would be required to both better position new zealand's primary industries, while also avoiding further environmental damage. in reorganising the bioeconomy to meet these challenges, building flexibility in future land and value chain options should be introduced to avoid new types of silos forming, while also improving natural resource base resilience to future shocks. new zealand has the required elements in a large and well developed biological resource-base, the necessary expertise and drivers, and the emerging impetus for system change. ironically, the current primary sector strength may be the prime inertia in the system towards enabling a new bioeconomy from forming. to fully transition to a functioning bioeconomy, new zealand will need to unlock and open the bounded edges that define its agricultural, forestry and marine sectors, to enable cross-fertilisation of ideas and technologies, as well as create less distinct sectoral boundaries that allow for penetration by new market players, particularly in the service and manufacturing industries. unlocking bounded systems to incorporate increased biotech capability and applications to flourish could lead to novel solutions to environmental restoration and regional economic growth for new zealand. finding ways of linking and connecting the primary sectors with the service and manufacturing sectors through the application of bioscience to non-primary markets is also critical. without whole of government support and interventions, shifting towards and realising the full potential of the new bioeconomy seems unlikely. while the ministry for primary industries has produced a defined strategy, it needs to lead rather than defer to the market-led economy, to support collaborative partnerships outside of primary industry silos and to integrate efforts for crossfertilisation amongst research and industry. the research needed to transition primary sectors towards higher value production may also be outside of the mainstream areas of current industry funding priorities, whose members have significant investment in the status quo. therefore ways to draw new investment into new zealand is required to fund high-risk bioscience and novel agritech. for new zealand to successfully transition and emerge as a global leader in the 'new' bioeconomy, the current bioeconomic direction will need to be radically transformed, repositioned and restructured, with existing efforts and trajectories integrated into a cohesive whole. it is likely that such transformation will not come solely from within the primary sectors themselves but from new thinking and niche activities that occur on the sectoral edges, particularly if these are allowed to blur and intermingle. connection of the strong existing regime with new niche players that emerge will enable cross sectoral interaction, new biobased activities and ideas. these will require support at governance level by a cohesive, overarching strategic direction and implementation policy for the nation. until government presents a joined-up, whole of government strategy and implementation pathway -one that includes incentives for international investment in agro-ecology and biotechnology and new economic models of regional wellbeing that focus towards self-sufficiencyit is unlikely that industry has the impetus to radically transform their current direction towards the new bioeconomy. research project tasks were shared equally amongst team members, with the following key oversights: bayne, market transition emphasis and manuscript lead; wreford, adaptation emphasis, survey design and overall project lead; edwards, policy and social licence emphasis; renwick, resource economics emphasis. commodity prices and the macroeconomy: an extended dependent economy approach driving economic growth through biobased industries the primary sector science roadmap -strengthening new zealand's bioeconomy for future generations. wellington: ministry for primary industries wellington: new zealand government oecd countries and emerging economiesparis enabling a transformation to a bioeconomy in new zealand economic plan for a productive, sustainable and inclusive economy wellington the growing us bioeconomy: drivers, development and constraints synthetic biology in the driving seat of the bioeconomy the bioeconomy to : designing a policy agenda plant biotechnology for food security and bioeconomy reconciling food and industrial needs for an asian bioeconomy: the enabling power of bioeconomy: shaping the transition to a sustainable, biobased economy a transition to which bioeconomy? an exploration of diverging techno-political choices what is the bioeconomy? a review of the literature the biobased economy in europe -hype or reality? perspectives for the baltic regions situation and outlook for primary industries. wellington: new zealand government pepanz. new zealand's consumption country report: new zealand- update. bioenergy policies and status of implementation wellington: government press biotechnz to survey nz biotechnology companies and supporting organisations ministry of business innovation and employment a strategy for a bioeconomy innovation cluster across yorkshire and humber bio-economy and the sustainability of the agriculture and food system: opportunities and policy challenges how the new circular bio-economy could deal with the problem of plastic strategic rationale for a bio-pilot plant hub for new zealand forestry will drive new zealand's circular bioeconomy -no twig or needle wasted yes, we can make money out of lignin and other bio-based resources potential bioplastics plant for marton gets government funding research nz herald online available from www.productivity.govt.nz/low-emissions wellington: new zealand government research book hamilton: our land and water farming for our future new zealand dairy farming: milking our environment for all its worth agricultural gdp catches well under one quarter of the agribusiness system why manufacturing really does matter estimation of consumer willingnessto-pay for social responsibility in fruit and vegetable products: a cross-country comparison using a choice experiment global food demand and the sustainable intensification of agriculture water quality trends in 's greenhouse gas inventory net zero in new zealand: scenarios to achieve domestic emissions neutrality in the second half of the century nz could buy time by planting trees -lots of them the future of food & the primary sector: the journey to sustainability competitive bioeconomy? comparing bio-based and non-bio-based primary sectors of the world natural capital and bioeconomy: challenges and opportunities for forestry indicators and tools for assessing sustainability impacts of the forest bioeconomy visions of sustainability in bioeconomy research bioeconomy policy in europe, germany and new zealand wellington: new zealand government charting a course: shellfish aquaculture and indigenous rights in new zealand and british columbia discourse, agency, and social licence to operate in new zealand's marine economy factors controlling the development of the aquaculture industry in new zealand: legislative reform and social carrying capacity examining residents' proximity, recreational use, and perceptions regarding proposed aquaculture development the burden of proof within the scope of the precautionary principle: international and european perspectives available at ssrn new zealand public acceptance of biotechnology new zealanders and biotechnology: attitudes, perceptions and affective reactions genetic modification technology and producer returns: the impacts of productivity, preferences, and technology uptake pernicious pests and public perceptions: wilding conifers in aotearoa new zealand the neoliberal underpinnings of the bioeconomy: the ideological discourses and practices of economic competitiveness european transitions towards a corporate-environmental food regime: agroecological incorporation or contestation? new zealand biotechnology strategy: a foundation for development with care. released governance of the bioeconomy: a global comparative study of national bioeconomy strategies oecd-fao agricultural outlook - . food and agricultural organisation of the united nations biotech an ailing area of nz economy collapse of icp biotech a sorry saga new zealand press association what went wrong at protemix unlocking our energy productivity and renewable potential -new zealand energy efficiency and conservation strategy - (nzeecs) the transition to a bio-economy: national perspectives new zealand's low emission future science investment fund in the preparation of this manuscript. key: cord- -gg qcpmz authors: rubin, geoffrey a.; wan, elaine y.; saluja, deepak; thomas, george; slotwiner, david j.; goldbarg, seth; chaudhary, salma; turitto, gioia; dizon, jose; yarmohammadi, hirad; ehlert, frederick; rubin, david a.; morrow, john p.; waase, marc; berman, jeremy; kushnir, alexander; abrams, mark p.; halik, carolyn; kumaraiah, deepa; schwartz, allan; kirtane, ajay; kodali, susheel; goldenthal, isaac; garan, hasan; biviano, angelo title: restructuring electrophysiology during the covid- pandemic: a practical guide from a new york city hospital network date: - - journal: crit pathw cardiol doi: . /hpc. sha: doc_id: cord_uid: gg qcpmz the coronavirus disease crisis is a global pandemic of a novel infectious disease with far-ranging public health implications. with regard to cardiac electrophysiology (ep) services, we discuss the “real-world” challenges and solutions that have been essential for efficient and successful ( ) ramping down of standard clinical practice patterns and ( ) pivoting of workflow processes to meet the demands of this pandemic. the aims of these recommendations are to outline: ( ) essential practical steps to approaching procedures, as well as outpatient and inpatient care of ep patients, with relevant examples, ( ) successful strategies to minimize exposure risk to patients and clinical staff while also balancing resource utilization, ( ) challenges related to redeployment and restructuring of clinical and support staff, and ( ) considerations regarding continued collaboration with clinical and administrative colleagues to implement these changes. while process changes will vary across practices and hospital systems, we believe that these experiences from different ep sections in a large new york city hospital network currently based in the global epicenter of the coronavirus disease pandemic will prove useful for other ep practices adapting their own practices in preparation for local surges. in march , new york city became the new global epicenter of the coronavirus (covid- ) pandemic. the exponentially rising new york city covid- caseload and the preceding experiences in china, italy, and washington state demonstrated a stark reminder that a catastrophe like a pandemic may potentially overwhelm even the most advanced health systems. in , during the influenza a (h n ) pandemic, the institute of medicine detailed "crisis standards of care," defined as a "substantial change in the usual health care operations and the level of care it is possible to deliver… justified by specific circumstances and… in recognition that crisis operations will be in effect for a sustained period." all medical departments in new york city instituted their respective crisis and contingency protocols while trying to maintain the highest possible quality of care for the upcoming months. in lombardy, italy, the unique organizational issues of an interventional cardiology department in treating patients during the pandemic crisis were recently described, including recommendations for patient riskstratification, cardiologist team reassignment, interhospital collaboration, and safety considerations. with regard to electrophysiology (ep) services, the surge in covid- activity in new york city presented multiple challenges, requiring considerable "ramp down" and structural reorganization specific to the field of ep, as many services do not remain idle during this time period. we describe the changes in usual operations implemented in our dedicated ep laboratory sections across the newyork-presbyterian (nyp) enterprise (i.e., columbia university irving medical center, weill cornell medical center, queens, and brooklyn methodist hospital). our collective experience across the nyp ep services may be representative of the rapid institutional changes that are required during a pandemic or national disaster. therefore, we believe that these details of "how to ramp down" can serve as a practical guide and be of particular interest to other ep sections as rapidly rising cases of covid- threaten other parts of the country. we additionally relay a handful of case scenarios from our experience that point out examples for how ep sections can prepare their policies and procedures (with prior cuimc institutional review board approval). understanding the potential scope of the covid- problem has been challenging at all levels of policy-making, including national, state, and local, and within individual organizations. in the early days of march , there was considerable debate across the country, including over social media, about the scope of scaling back and reprioritization of services, including whether nonurgent ep procedures should be postponed. although the answer to these questions seems obvious in retrospect, the timing of when to begin canceling cases has often been staggered and made at the local level. to offer an example of the global sense of how the covid- crisis has impacted our hospital network, as of the writing of this article on april , , the entire nyph medical system (which includes more than these hospitals) reported covid+ inpatients ( at columbia, at weill cornell, at queens, at brooklyn methodist, and remainder at affiliate hospitals); a total of of these patients were located in icus given the severity of their illnesses. to meet these demands, one goal of the network has been to increase intensive care unit (icu) bed capacity from a baseline of approximately icu beds to over icu beds, a herculean task requiring a complete transformation of all hospital resources, including staff duties and physical plant. we describe the pivoting of operations within the context of broad categories of reorganization, including ( ) procedure-related and inpatient care, ( ) outpatient care, and ( ) administrative restructuring. we follow the recently consolidated hrs/acc/aha covid- practice guidance. such a rapid and complete ramp down requires effort to communicate with and reassure scheduled patients that the procedure can be safely postponed. in reality, a decision about procedure triage is not necessarily a black and white one but includes shades of gray. for example: • we adopted a policy to perform procedures only in patients felt to have a likelihood of significant clinical deterioration within a short period of time, which has varied, depending on local availability of ancillary staff and ppe resources, from between hours to - weeks. • all other prescheduled elective cases have been canceled without a reschedule date. • direct admissions or transfers are very limited, given the surge of ed patients requiring admission. • as procedural areas have been converted into icus, the availability of procedural space for ep procedures must be carefully discussed with hospital leadership. the ep procedural volume has decreased along with the overall non-covid+ volume in the hospital. in our experience, lab volume has decreased by %- % across all sites. the majority of procedures performed are implantable devices, predominantly permanent pacemakers (ppms) for high-grade atrioventricular block (avb). across our institutions, to date, only one ablation has been performed, which occurred just before the start of the patient surge. one device system extraction due to recalcitrant sepsis with a visible lead vegetation was performed. patients with ventricular tachycardia (vt) have been to date managed medically, usually with amiodarone (and in many cases as outpatients with frequent follow-up, as described below). as the time spent operating under these conditions increases, we anticipate the increased possibility that patients will breakthrough medical therapy and require ablation therapy. in short, if the case is not urgent, it is not done. workflows that have been ingrained for years all need to be reconsidered. for example, we maintain one operational ep lab at each center, sometimes shared with cath lab colleagues. in order to preserve ppe, and because staff, including specialized scrub technicians and nurses, have been "redeployed" to other units, we function by the mantra, "if it can be done by one person, then it should be done by one person." cases are performed by a single attending. a surgical mask is placed on all patients, and if a patient's respiratory status is in question or tenuous before a procedure, then consideration of endotracheal intubation is discussed before patient transport to minimize aerosolization risk in the lab. n masks are used by operating physicians for all cases. as many anesthesia teams have been redeployed to assist with central lines and intubations, conscious sedation administered by the ep md (with backup anesthesia services) is utilized if felt to be a reasonable option that does not compromise patient safety. frequent updates are required for appropriate communication in the era of social distancing, including updates regarding staff who are ill and not able to work. for example: • daily morning meetings, conducted by videoconference, have allowed for the ep attendings, as well as nurse practitioners and administrative staff, in the columbia practice to remain in active communication. this venue allows for discussion of challenging cases, deliberation of how to message recommendations in a unified way (e.g., regarding covid-related consultation questions), schedule shared responsibilities, and contingency plan. smaller ep groups remain in communication via telephone. • preplanning and coordination of urgent procedures with colleagues of other disciplines, including anesthesia, nursing, blood bank, backup surgery (the latter for urgent extractions), allows for these representatives to deploy already stretched staff/resources and expedite throughput of patients. • discussion and coordination with colleagues in other hospitals allow for "reality checks" regarding local practice patterns, and brainstorming of strategies to address shared challenges. the following is a summary of significant lab practice changes, specific cases, and "pearls" from our collective experience: • one area of deliberation has involved the timing of stable pacemaker-dependent outpatients with devices at elective replacement interval (eri). as there is variation between companies in battery longevity and case reports of rapid unexpected battery depletion after eri and remote monitoring interrogations may further deplete the battery, we recommend performing a generator change within month after the onset eri in these patients, which we believe is in keeping with the hrs/acc/aha guidelines which classify these cases as non-elective/urgent. a list of patients monitored at home with devices around eri should be maintained, so accurate contact information is important. • we have performed implantable cardioverter-defibrillator (icd) placement on stable outpatients wearing an external icd and awaiting a permanent implantable device or inpatients with multiple episodes of nonsustained vt and systolic dysfunction (hrs/acc/aha classification as semi-urgent ). device implantations are discharged the same day, when feasible, and ideally with remote monitoring capability. • in the case of a covid-negative patient presenting to the hospital in high-grade avb, we arranged to perform an expedited same-day ppm (including lab team mobilization on weekends). similarly, we are prepared to perform same day and secondary prevention icd placement in heart failure patients with vt. • in the case of an unstable transcatheter aortic valve replacement at high-risk for avb, we coordinated with the structural © wolters kluwer health, inc. all rights reserved. www.critpathcardio.com | valve team to be on-site and perform a ppm immediately following valve deployment in the same operating room if the patient developed irreversible avb, facilitating same-day discharge. coordination between cath and ep nursing (if not cross-trained) must be considered, as nursing staff may have been redeployed to other units. • for atrial fibrillation with rapid ventricular response refractory to medical therapy requiring cardioversion, computed tomography angiography scans are used (whenever possible) to ruleout left atrial appendage thrombi instead of transesophageal echocardiograms to minimize aerosolized exposure to transesophageal echocardiograms and anesthesia staff. intracardiac echocardiogram to assess for thrombus has also been considered for appropriate candidates. • attempt to perform device interrogations remotely. it is important to coordinate as early as possible with all device companies, as well as with clinical colleagues in the emergency department (ed), to establish remote monitoring capability in the ed and even icus. indications for interrogation are limited to frank syncope, documented device malfunction, recurrent icd shocks, need for a program change, and rule-out atrial fibrillation/flutter + cryptogenic stroke. • we have rotated device representative assistance in an effort to minimize exposure risk. • for hospitals that do not routinely perform device implantations on weekends, implement a strategy of opening the ep lab during this time period to implant a ppm in avb patients and expedite patient flow/free up icu bed space. • urgent device implants have been performed while tolerating higher than usual international normalized ratios (e.g., international normalized ratio > . ), when benefit:risk ratio deemed appropriate. • some patients have had procedures, including generator changes and direct current cardioversions, performed outside the metro new york area to minimize exposure risk and preserve ppe and other hospital resources. inpatient consult volume has diminished to approximately / of its baseline during the pandemic. consultations are evaluated by one person to minimize exposure. based on guidance regarding emergency healthcare provision during this crisis in the state of new york, if in-person consultation is not deemed to be necessary for diagnosis and treatment, then provider discretion is used to forego such potential exposure. careful attention to communicate case presentations and recommendations thoroughly among consulting teams, consultants, and patients is paramount. real-world applications of these points include: • consults are performed remotely if possible via the electronic medical record, including health insurance portability and accountability act (hipaa)-compliant texts of electrocardiograms (ecgs) and telemetry strips sent to the consultant via the media section of the emr. some centers have remote access to inpatient telemetry. telephone consultation with covid+ inpatients (when possible), as well as discussions over the phone with family/friends (who are not able to remain with patients during this time period), has been utilized. • in the case of covid-positive patients, we use telemetry to determine the rhythm and measure the qtc, preferably with lead ii. covid- related consults have included atrial fibrillation, atrial tachycardia, sinus arrest, accelerated idioventricular rhythm and vt in patients with myocarditis, and qtc prolongation with torsades. • physician protection is paramount, and refresher web-based videos of donning and doffing were reviewed by all clinical staff. step : set up telehealth and address its challenges with the onset of the covid- pandemic, telemedicine across the country advanced dramatically within week. guided in part by changes in billing restrictions regarding televisits, as well as hipaa restrictions, we transitioned nearly all patients to telehealth visits using videoconferencing capability native to electronic medical record system or using third-party video applications. a summary of outpatient challenges, considerations, and recommendations is presented in table . for front-end staff: to facilitate remote "work from home" ep, some challenges and solutions have included: • for staff without access to appropriate computer equipment, the division purchased and loaned ipads for some staff at one hospital to perform televisits and loaned laptop computers for other staff who needed to access the electronic record system. • recognize the increased efforts required to ( ) contact patients to shift previously scheduled outpatient in-person visits and device checks to televisits, ( ) remind patients not to come to clinic in-person, ( ) obtain appropriate training to accommodate this change in workflow, ( ) have staff guide patients through the process of being televisit-ready. additional staff (e.g., medical assistants) are often required to be deployed to accomplish these tasks. • coordination of call-forwarding of office numbers and fax management to staff now working from home. • brainstorming flexible work solutions for those staff now with children at home from school or ill relatives needed to be addressed. our network has been heavily involved in coordinating and communicating options to staff. • working with informational technology (it) staff (who themselves required additional support due to increased demand) to ensure adequate password access, virtual private network (vpn) access, and access to all required remote systems from home. • while supporting flexibility and addressing barriers to homebased work, reinforcing the need for prioritization of workrelated commitments while based in a home environment. • reaching consensus regarding changes in workflow patterns, including televisits, that are occurring due to the covid- crisis. interestingly, whereas in the past, patients were resistant to setting up telemedicine, we have found that patients are now amenable to this option and have expressed satisfaction with reduced travel time and peace of mind regarding social distancing. for clinical providers performing televisits, potential challenges and solutions of rapid adaptation to telehealth have included: • review if and how it is possible to perform televisits through the electronic medical record system, if possible. • in this crisis setting with relaxed hipaa regulations, other third-party applications have also been utilized for televisits, and specific accounts have been opened for each attending, with a discussion of individuals' preferences. all video conference visits have been deemed eligible for reimbursement by centers for medicare & medicaid services, provided that documentation confirms the patient consented to telemedicine and specifies the time spent in consultation. documentation of televisit type is noted in case other modalities, such as telephone visits, are deemed acceptable for billing. • if smartphones are used, consider whether personal phone number is viewable while using these different modalities. for patients, the following potential challenges and solutions have included: • each patient's televisit capabilities must be assessed. some patients may not be technologically adept, or not have access to a smartphone, laptop, wifi, or e-mail. although a telephonebased evaluation is not reimbursed at this time, we have found it is still an effective way to provide care to anxious patients who are unable to access telehealth in other ways. we have found that the following basic telemedicine "pearls" help smoothen the experience for patient and caregiver: • communicate an exact time when the patient should log in to prevent miscommunication. remind patients that providers may be late to calls, and to please allow for a certain time period to lapse before logging off. • consider enlisting family members to assist patients requiring technical help to initiate or complete a visit. • when speaking to the patient, look directly into the camera on your computer to simulate eye contact. explain to the patient that if you look away, it is to take notes. • ensure appropriate lighting is present in the physician's home "office" space. • patients transmitting remotely who were coming for an annual visit were rescheduled for a time in the distant future with continued remote monitoring; patients who had remote monitoring-capable devices but were not enrolled were called by an md or np and encouraged to enroll, and a remote monitor was sent to them; patients with devices incapable of remote monitoring were scheduled for an outpatient session in the future, with timing dependent on prior history, including estimation of battery life. • postprocedure "wound care" follow-up has been accomplished through a dedicated, staffed e-mail address where patients may send photos of their wound site. rapid provision and in-servicing in the use of remote home interrogators is imperative, as patients can send remote downloads from their home monitors to serve as postprocedure interrogations. • apple watch, kardia recordings, and mailed holters and patch monitors have been used to assess for arrhythmias and to follow the qt interval. remote ecg transmissions have been useful to document exacerbations of arrhythmias, such as atrial fibrillation, in otherwise stable outpatients, as well as provide reassurance to those patients with heightened anxiety in general during the covid- crisis. • when higher-risk patients are seen in person, the ep administrative staff is informed. a screening for covid- symptoms must be performed before the visit. if possible, efforts should be made to have the consult at a less utilized "off-site" away from the hospital. at least one hospital has transitioned all outpatient visits off-site, as this option was felt to minimize exposure risk to outpatients (versus a facility with a high percentage of covid+ patients). • examples of patients who had in-person appointments during the covid- surge in our system include assessments for patients with a concern for radiation skin injury after prolonged biventricular device placement, poor wound-healing in a device patient that required cleaning and adhesive, a thorough device interrogation in a ppm-dependent patient with a question of rv lead integrity, and an icd interrogation for a patient with a lead conduction fracture and increasing episodic noise. • lastly, it is an enormous challenge to manage patients who are shocked by their icd at home during the covid- pandemic. in our experience, due to patient reluctance and/or limited availability of ed and inpatient resources, cases ordinarily managed with ed visits/admissions or direct admissions may not be possible. to date, of patients with multiple icd shocks due to vt, all were medically managed after presenting to the ed for assessment of vitals and baseline laboratory testing and released home with careful follow-up, without inpatient admission. examples include: • a patient with history of familial dilated cardiomyopathy and a subcutaneous icd received successive shocks for monomorphic vt. he was advised to take an extra dose of carvedilol and was transported by ambulance to a local ed, where he received an intravenous amiodarone load and was discharged on oral amiodarone hours later without recurrent events, with plan to follow-up at a later date, as medical resources allow. • a patient with history of ischemic cardiomyopathy and a single lead icd was brought to a network hospital site after receiving shocks for monomorphic vt in the ventricular fibrillation zone in the setting of medication noncompliance. he received intravenous amiodarone mg bolus and hours of an infusion at mg/min before being discharged on metoprolol and oral amiodarone load. • md scheduling: given the dramatic decrease in ep-centered patient volume, each on-call physician is involved in direct patient care at each hospital. as mentioned above, one attending performs procedures alone, with a backup physician available for assistance if needed. this system allowed for the flexibility of physician staff to continue to attend to their prescheduled responsibilities, including outpatient telehealth visits and inpatient rounding within the cardiology division, and to record staff available for possible redeployment. • contingency planning for deployment and illness: continuous flexibility regarding the rotation of md staff should be maintained to adjust for physicians who fall ill or are redeployed in other areas of the hospital system, including ready availability of staff. • internal redeployment: providers and staff (physicians included) with patient-facing duties who have relevant medical comorbidities, and/or older age have been redeployed to nonpatient-facing duties, including -covering inpatient as well as outpatient remote televisits, including for colleagues who have been redeployed -talking to patient families over the phone who are unable to be physically with their loved ones in the hospital -fielding overnight and weekend calls to relieve inpatient-based colleagues -curbside consultations with junior ep staff members -continuing teaching duties of trainees when appropriate -administrative scheduling (i.e., to see patients remotely, talk with patients' families). practically, we have created a schedule to delegate and track specific responsibilities for each md that is accessible through a shared ep drive or the internet, with the goals of transparency and equitable balance of responsibilities. this has allowed for regular updating, including • one procedure attending in-house per day for procedures, clinic or floor work • one attending at home for procedural backup • remaining attendings and fellows on a list to be deployed to non-ep areas (e.g., icu/expanding icd footprints or clinic as needed due to the expansion of icu units, hospitalists, and general medicine services). • contingency planning for fellows and non-md staff: other staff members' responsibilities have also changed considerably, often directed by hospital leadership, including department chiefs. these include: • emergency temporary attending privileges have been granted to fellows in their board certified/eligible fields. • nurse practitioners and physician-assistants have been transitioned to outpatient remote practices and also redeployed to surging eds, cough/fever clinics, and icus. • contingency planning for coverage of fellow duties and nonclinical staff is considered on a daily basis. • satellite offices have been consolidated to minimize exposure risk and allow for redeployment of staff to other needed areas. each deployment is managed centrally in conjunction with the cardiology and medicine divisions, depending on the particular needs of the hospital, and staff has also been deployed to hospitals within the network, as emergency privileges for all clinicians within the network hospitals were authorized. further staff responsibilities include designating colleagues to coordinate research efforts with institutional review board and other departments on topics of more urgent covid-related interest (e.g., qtc in the setting of covid- treatment, obtaining -lead ecgs off telemetry in units since unable to perform frequent -lead ecgs on covid- patients). lastly, but certainly not least in importance, is the need for regular, -way communication between sections and hospital leadership (fig. ) . for larger ep practices, we recommend that at least one staff member directly communicates with hospital and clinical division leaders each day for several reasons. these communications allow ep staff to: • understand and appreciate the broader institutional picture, including the scope of the pandemic and its impact on the network • discuss resource use and capacity • discuss staff allocation, challenges, and illnesses • troubleshoot daily clinical and administrative challenges • provide and receive feedback in the setting of altered workflows • convey that ep practices are relatively smaller compared with other services, and deployment needs of the hospital should be balanced with the need for availability of a core number of ep staff with specialized skills necessary to perform urgent/emergent ep procedures • coordinate staffing changes regarding ill/exposed staff members from workforce health & safety and infection prevention & control departments. • obtain information regarding possible housing, travel, and meal options for staff, including ( ) the provision of temporary housing while working and unable to travel back-and-forth, or desiring of isolating from loved ones at home, ( ) reimbursement of parking expenses for staff who normally travel without vehicles, ( ) shuttle schedules for urban commuters, and ( ) meal provisions while at work. these resources have been provided to us by the network system, including temporary housing provision for over staff members. all this information is relayed during a daily ep section videoconference. the point-person is responsible for communicating directly to hospital/clinical leadership. one procedure attending in-house per day one attending at home for procedural backup; (others on a redeployment wait-list) remaining attendings/fellows on a list to be deployed to non-ep areas elderly, at-risk physicians reassigned to televisits, overnight calls, teaching duties, curbsides from ep in-house colleagues emergency temporary attending privileges granted to fellows contingency planning for coverage of fellow duties considered on a daily basis designate colleagues to coordinate research efforts with institutional review board practically, our shared morning workflow proceeds as follows: • holding a regularly scheduled video conference among physicians and ancillary staff to discuss health check-ins, hospital capacity updates, and procedural and ethical discussions. an agenda is circulated before each meeting, and minutes are kept. depending on local staffing and workflow, frequency of meetings has varied from daily to a few times per week. • video conferences allow for the continuation of fellow education conferences, which are performed remotely with powerpoint lectures and electrogram-based "quizzes." • solicit questions, suggestions, and feedback, including reviewing the importance of appropriate ppe use, as well as experiences and best-practice tips for donning and doffing ppe. we find that these daily meetings also present a much-needed opportunity to decompress and maintain positive morale among staff, as more deliberate communication with colleagues is necessary to overcome the physical barriers to "curbside encounters" imposed by social distancing. striving to maintain regularly scheduled weekly electrogram conferences and case reviews helps to maintain a sense of camaraderie and "normalcy" during these challenging times. during the covid- pandemic in new york city, restructuring in the form of multiple "ramp down" and pivot modifications have been rapidly applied to the ep services across the nyph hospital system, resulting in deployment of ep resources in a streamlined but not idle fashion. it is obviously better to prepare in advance for such ramp down, with contingency protocols in place before the covid- pandemic reaches a hospital system. we understand that not all ep practices are the same, and groups will face different challenges, including managing the financial burden and sequelae of decreased volume, as well as the possible "second surge" of both inpatients and outpatients who have remained at home with ep disorders until peak covid- surging has dissipated. nevertheless, we hope our experience is useful for ep sections in other parts of the country and world who, unfortunately, anticipate an influx of covid- cases. as we learn from each other how to face an unprecedented modern pandemic, continued communication, collaboration, and preparedness are critical to helping our patients and each other. committee on guidance for establishing standards of care for use in disaster situations. guidance for establishing crisis standards of care for use in disaster situations: a letter report critical organizational issues for cardiologists in the covid- outbreak guidance for cardiac electrophysiology during the coronavirus (covid- ) pandemic from the heart rhythm society covid- task force; electrophysiology section of the american college of cardiology; and the electrocardiography and arrhythmias committee of the council on clinical cardiology unpredictable battery depletion of st jude atlas ii and atlas+ ii hf implantable cardioverter-defibrillators department of health & human services. notification of enforcement discretion for telehealth remote communications during the covid- nationwide public health emergency standard and precordial leads obtained with an apple watch covid- and the risk to health care workers: a case report older clinicians and the surge in novel coronavirus disease (covid- ) key: cord- - x pe qd authors: wainwright, claire e title: new therapies for people with cf in the cftr modulator world date: - - journal: j cyst fibros doi: . /j.jcf. . . sha: doc_id: cord_uid: x pe qd nan cftr modulation has led to improved health outcomes for patients with cf, although the benefits derived from cftr modulation have also led to difficulties in the design of clinical trials for new medicines. established trial endpoints may not be as sensitive to change in healthier populations, and new outcomes or biomarkers may be required. patients may be less inclined to stop effective treatment for clinical trials, and this makes gold standard placebo-controlled trials more challenging. de boeck et al . provides the summary of discussions from a workshop held in november that focused on drug trial design in the new era of cftr modulation. the workshop included invited clinical experts as well as representatives from pharmaceutical companies, the european medicines agency (ema), experts in health technology assessment and patient organisations [ ] . there were welcome discussions on trials and approaches to drug development for groups such as those with rare cftr mutations and vulnerable groups such as infants and young children. infants and young children require special consideration as they may derive the greatest benefit in the long term from early improvement of cftr function, although early exposure may also increase the potential for greater harm given the developmental context. measuring efficacy in uncooperative young children also presents many challenges, and there are time constraints to understanding longitudinal safety and outcomes. regulatory requirements for drug development vary between different countries. these differences lead to barriers for drug development and contribute to reduced global access and increased costs associated with drug development. harmonization between regulatory authorities should provide agreement on the technical and marketing requirements for therapeutic products. this requires cooperation between the regulatory authorities working with pharmaceutical companies to achieve an agreed pathway for the ethical development of new therapies and reduce both duplication of effort, and the time taken to bring a product from bench to bedside across different jurisdictions. globally there are those who are living without access to new cftr modulation, or other new medicines, because of regulatory issues as well as the cost of these expensive treatments. mayer-hamblett et al . reflect the discussions and outcomes from a workshop of invited international experts on clinical trials and trial networks that was held in october associated with the north american cf meeting [ ] . the workshop focused on the development of new therapies for cf and discussed the challenges and approaches to regulatory requirements in the post cftr modulator environment including treatments for rare mutations. the workshop highlighted the crucial importance of clear communication between all stakeholders. the workshop also provided strategies for the development of new anti-infective, anti-inflammatory and other symptomatic treatments, as well as for the development of new cellular therapies that would be impacted by the availability of cftr modulation. regulatory authorities have started to find solutions to some of the challenges raised in both the workshops. the food and drug administration (fda) in took the step of approving the potentiator ivacaftor for an extended list of cftr mutations based on laboratory studies rather than specific clinical trial evidence. the premise for this decision was that clinical trials for many rare cftr mutations would not be feasible, and that cell models of functional cftr responses were generally predictive of the clinical benefits [ ] . this approach will need careful consideration and agreement on which cellular approaches are required, and for which therapies they are appropriate in the future, but this has certainly opened a new door for drug development and regulatory approval. during the peer review process, an issue arose around the terminology used in both manuscripts. this led to considerable debate between the authors, the reviewers and the journal, and given the strong opinions around the terminology, it may be worthwhile to reflect on this debate. both manuscripts initially used the term "highly effective cftr modulators" to identify the exceptional outcomes from two cftr modulators currently in clinical use. the two cftr modulators include ivacaftor in patients with cftr gating mutations [ , ] , and the triple combination elexacaftor, tezacaftor and ivacaftor (trikafta tm ) in patients aged years and older who are either homozygous [ ] or heterozygous for f del-cftr [ ] . two other cftr modulator therapies in clinical use, orkambi tm , and symdeko tm (also known as symkevi tm ), are associated with more modest improvement in cftr function and clinical outcomes [ , ] . given this background, and the growing common usage of this terminology, why should there be any concern about the use of "highly effective cftr modulator" to differentiate these drugs in the scientific literature? drugs are classified based on their pharmacological effects, their chemical structures, molecular targets or specific drug actions, and the recognised classification of "cftr modulators" fits nicely within this approach. as clinicians and scientists, we describe and compare specific drugs in terms of their potency, effect or toxicity and such comparisons and discussion are critical in developing appropriate clinical use. to date, however the classification of drugs has not included adjectives that describe them. new cftr modulators are in development and, like other new drugs, may end up being equivalent or may be more, or may be less effective for specific outcomes compared with the various current clinically available cftr modulators. if we start to differentiate within the cftr modulator class in the scientific world by the term "highly effective', what will we use to set the bar to achieve this accolade, and could there be consequences to doing this? how will we account for variation in effects on different outcomes or between individuals? naming or labelling things is a very powerful tool that is well recognised in the advertising world. in the clinical trial setting there has been concern around the explosion in the use of acronyms for naming clinical trials and the risks that positive sounding trial acronyms pose with regards to the therapeutic misconception [ ] . the language of science should be clear and objective while still providing the opportunity for creative thought, but the labelling of drugs as "highly effective" as part of their classification feels close to leaving objectivity behind. the global sars-cov- pandemic emerged after both workshops. the pandemic has led to substantial impacts on health and on the global economic outlook. it is likely that there will be repercussions felt across all sectors of the economy, including drug development and support for clinical research. what this means for cf research and the pipeline of new treatments for cf specifically, or indeed for how clinical trials will be conducted, or new therapies may be reimbursed in the future, remains to be seen. the pandemic however has prompted urgent collaboration globally to develop vaccination and treatments to combat covid- , the disease caused by sars-cov- . in june , a great start was made in regulatory harmonization with a meeting chaired by the fda and ema under the auspices of the international coalition of medicines regulatory agencies (icmra,) which brought together experts from over countries and regulatory authorities. the meeting led to broad agreement on the data required from laboratory, animal and human research as well as aspects of phase clinical trials aimed at the rapid development and regulatory approval for vaccines for covid- . we can only hope that this example of global collaboration will lead to a more established pattern of harmonization and more rapid development of other important medicines in the future. the outputs from the two workshops have provided a very helpful start in setting the scene for clinical development of new treatments for cf in the cftr modulator era. there were some issues however that may benefit from further consideration in the future. the high cost of new treatments and reimbursement remains a considerable concern for cf care. this of course is a thorny global issue for all areas of health worldwide, and while there are no easy solutions, we need to keep reconsidering the issues and chip away at the problem. the other major area that deserves further thought includes trials and regulatory pathways for new medicines in vulnerable groups such as pregnant or lactating mothers, those with solid organ transplants, and those with severe liver disease. these groups are almost always excluded from clinical trials and regulatory packages although clinicians and patients may choose to use the medicines once they are generally approved. there has been some encouraging progress recently with the fda guidance on the issue of trialling and monitoring medicines during pregnancy and lactation. future collaboration and communication between regulatory authorities, pharmaceutical companies, clinicians and patient groups will be needed to consider how best to establish the clinical use of new cf medicines for these very challenging populations. there has been enormous improvement and exciting development in cf care especially with cftr modulation, but much work remains to be done to ensure equi- cystic fibrosis drug trial design in the era of cftr modulators associated with substantial clinical benefit: stakeholders consensus view building global development strategies for cf therapeutics during a transitional cftr modulator era the u.s. food and drug administration's experience with ivacaftor in cystic fibrosis. establishing efficacy using in vitro data in lieu of a clinical trial a cftr potentiator in patients with cystic fibrosis and the g d mutation efficacy and safety of ivacaftor in patients aged - years with cystic fibrosis with a g d mutation efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the f del mutation: a double-blind, randomised, phase trial elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single phe del allele lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for phe del cftr tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for phe del acronyms confuse everyone: combating the use of acronyms to describe paediatric research studies key: cord- - bh authors: smithgall, marie c.; whittier, susan; fernandes, helen title: laboratory testing of sars cov- : a new york institutional experience date: - - journal: nan doi: . /j.yamp. . . sha: doc_id: cord_uid: bh nan title, status or ethnicity. • there are two main categories of tests used to detect current or past viral infection: molecular and serologic assays. • molecular assays aim to determine if a patient is actively infected with a pathogen of interest, while the purpose of serologic testing is to determine prior exposure. • serological assays determine a patient's exposure history. at this time, it is unknown whether antibody detection equate to immunity. (eua). perhaps the most noteworthy outcome is that this scenario has made laboratory professionals more visible and respected and induced a deeper sense of ownership of the profession. this brief report will provide an overview of the types of testing available for sars-cov- patient management, as well how testing has impacted the situation in new york city. clinicians rely on laboratory testing to provide clinically relevant, actionable results, which can direct both inpatient and outpatient care. there are two main categories of tests used to detect current or past viral infection: molecular and serologic assays. antigen-detection assays have also been used historically for diagnostic purposes. molecular assays aim to determine if a patient is actively infected with a pathogen of interest, while the purpose of serologic testing is to determine prior exposure. the most widely used assays for detection of sars-cov- utilize reverse transcriptase polymerase chain reaction (rt-pcr). this technique is already commonly used in microbiology laboratories to detect rna specific to respiratory viral pathogens, such as influenza, respiratory syncytial virus (rsv), and others [ ] . the world health organization developed the first quantitative rt-pcr test for detecting sars-cov- and subsequently the u.s. centers for disease control and prevention (cdc) began shipping its own rt-pcr test kits after receiving emergency use authorization (eua) by the u.s. food and drug administration (fda) on february , . however, there were complications that became apparent during the validation process that caused a setback in deploying the assay to the diagnostic community [ ] . on february , the wadsworth center of the new york state department of public health's rt-pcr assay was the second test to receive eua. this assay, though, was not designed for high-throughput testing, and analyzed approximately - specimens per day per platform with a turn-around-time of - hours from sample to answer. consequently, testing remained at a minimum until mid-march when commercially-available, fully automated sars-cov- real-time assays began receiving eua. these high-throughput automated assays include, but are not limited to, the cobas® sars-cov- test run on the roche cobas / platform and the abbott realtime sars-cov- assay with the m platform. rapid point-of-care tests such as xpert® xpress sars cov (cepheid) and id now tm covid- (abbott), which test single specimens, also became available. these molecular assays detect various viral targets including sars-cov- specific targets such as orf a/b, a non-structural region and n , a nucleocapsid recombinant protein as well pan-sarbecovirus targets such as the envelope e-gene. the ability to batch samples greatly increased testing capabilities in new york city. however, due to significant shortages of testing reagents, positive controls, collection swabs, transport media and personal protective equipment, only the most critically-ill patients presenting to the hospital were being tested. as a result, the biased positive rate of patients tested in new york state was around % and new york city was upwards of %. this crucial shortage in testing capacity significantly impacted the public health response's ability to contain the virus. the number of sars-cov- positive cases increased exponentially in new york and adjoining states such as new jersey, making this region the epicenter of the pandemic (fig. ). with the increase in the number of assays that were verified in several hospitals and laboratories within new york, testing was gradually expanded in april , beyond individuals with a very high pre-test probability, to include all symptomatic individuals and people with exposure to known sars-cov- . with this increase in the overall number of tests performed, the overall positive test rate decreased to approximately %, a more accurate reflection of the incidence of patients suffering from covid- ( figure ). with practicing of social distancing and contact precautions, in addition to expanded testing, the positive rate within the ny community has remained steady since early may , at about - %. the overall statistics for new york from early march until may th , can be visualized in figure . briefly, since the start of the pandemic, over million tests have been performed with an overall positive rate of approximately %. in terms of demographics, not only was incidence higher in males, but they also had a much higher fatality rate ( . %) compared to females ( . %). communities of color and lower socioeconomic status also were more seriously impacted with higher rates of infection and mortality [ ] . to date there are more than commercial laboratories and/or test kit manufacturers that have received approval for emergency use by the federal drug administration (fda) for sars-cov- testing with molecular assays accounting for the vast majority [ ] . various reports document success with different specimen types ranging from nasopharyngeal, oropharyngeal, anterior nasal and mid-turbinate nasal swab, swabs to nasal washes and saliva, some of which have received eua [ ] . in addition, the fda recently granted eua for an rt-pcr lab developed test for qualitative detection of sars-cov- in saliva specimens and a test that uses a home collection kit with nasal swabs [ ] for details see https://www.fda.gov/emergency-preparednessand-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization]. a recent report showed comparable detection of respiratory viruses by rt-pcr with saliva and np specimens [ ] . saliva as a specimen type, is appealing for its reduced risk posed at the time of collection; however, larger studies comparing saliva with other validated specimen types are essential for documenting the reliability of this specimen type. in an effort to expand testing capabilities, manufacturers and laboratories have adopted self-collection devices using predominantly anterior nares and mid-turbinate for sample collection [ ] . the wide range of specimen types and their varied collection times during the course of covid- infection however, could contribute to the false negative rates seen in the rt-pcr assays. in fact, a recent study demonstrated that false-negative rate for sars-cov- rt-pcr testing can be as high as % in individuals tested up to days after exposure and % in cases tested days post exposure [ ] . acceptable nasopharyngeal (np) and oropharyngeal (op) swabs are made with materials such as dacron and rayon, since they do not inhibit the pcr reaction. while specimens collected with np and op swabs differ in tip size and flexibility, both have been used to successfully collect specimens for identification of sars cov- [ ] . other specimens validated by different laboratories include nasal swabs, nasopharyngeal or nasal washes/aspirates, sputum, saliva and bronchoalveolar lavage [ ] . since each of the specimen types examines different anatomic areas with variable levels of viral inoculum, the possibility of false negative results should be ruled out for optimal patient management. the np swab remains the "gold standard" specimen source. transport medium for swabs are reagents that retain virus viability in the specimen and minimize bacterial overgrowth for the time necessary to transport it to the clinical laboratory. evaluation of different types of transport media including but not limited to viral transport media and universal transport media, showed that specimens consistently yielded amplifiable rna with mean ct differences of < over the various conditions assayed, thus supporting the use and transport of alternative collection media [ ] . for sars cov- , the fda has strongly recommended that viral culture not be performed. thus, alternatives to classical viral transport media have been validated in light of media shortages. these include normal saline, amies transport media and hanks balanced salt solution. a caveat to interpreting molecular results is that it can be difficult to ascertain whether a patient has an active infection or was previously infected. molecular assays can detect viral rna both when patients are actively shedding the virus (current infection) or have residual viral rna present. therefore, these assays are most useful in acute settings to detect patients with sars-cov- , where the results can optimize potential therapy and isolation protocols to ensure that appropriate personal protective equipment protocols are utilized for containment of the virus. in addition to rt-pcr, reverse transcription loop-mediated isothermal amplification (rt-lamp) technologies with increased levels of sensitivity, have shown utility, in resource-limited settings [ ] . notably, the first test using crispr (clustered regularly interspaced short palindromic repeats)-cas based technology for sars-cov- detection was recently granted eua (sherlock biosciences). the test has a limit-of-detection of viral copies and involves a two-step process, where sars-cov- rna undergoes rt-lamp followed by transcription of the amplified dna which activates crispr cleavage of reporter genes resulting in a fluorescent readout. the entire process can be completed in an hour [ ] . tests that use high-throughput sequencing of the sars-cov- genome are also being utilized in a research setting. these tests give additional information on viral mutations and can trace the global evolution of the pandemic. point-of-care (poc) testing is beginning to be available for sars-cov- . poc testing refers to a broad category of diagnostic tests that can be performed where patient care occurs. however, due to evidence that samples collected in transport media may fall below the assay's limit of detection [ ] [ ] [ ] [ ] , the eua for this test was modified for testing only from direct swabs. preliminary data though indicates that despite this modification, the abbott id now tm covid- had a significant false negative rate when using dry nasal swabs [ ] . some additional rapid assays that are commonly used are the xpert® xpress sars cov (cepheid) and the biofire® covid- test. the other major type of diagnostic assay is serological. these assays determine a patient's exposure history. at this time, it is unknown whether antibody detection equate to immunity. these assays detect the presence of antibodies against sars-cov- antigens in a patient's serum. there is a delay between the initial viral infection and the production of antibodies by the immune system. during this time, termed the "window period," a patient who is infected with sars-cov- , but has not yet produced antibodies, would test negative on such an assay. as the immune system mounts a response against the virus, igm antibodies are initially produced, which are short lived, followed by a more durable igg antibody response [ figure ]. therefore, serological tests may be unique to one class of immunoglobulins or detect multiple and can typically be completed in - hours. currently, there are at least eua serology assays, some of which are automated [ ] . most commercial serological sars-cov- assays use a lateral flow assay technique and format, and for many of these there are unsubstantiated, or even false, claims about test performance [ ] . the estimated median seroconversion time is - days with virtually all covid- patients producing detectable antibodies approximately days after onset of symptoms [ ] [ ] [ ] . therefore, these assays will be most helpful in determining an individual's exposure status and perhaps in assessing their immune response to sars-cov- . going forward, these assays can be particularly helpful in identifying sars-cov- cases in individuals who may have had symptoms consistent with sars-cov- but were never tested with an rt-pcr assay, as well as individuals who may have had asymptomatic infection. given that ~ % of sars-cov- cases are mild to moderate in severity [ , ] , and that molecular testing has predominantly been restricted to the most severely ill patients, the true number of sars-cov- cases is likely to be vastly greater than that available from molecularly-confirmed case counts. thus, serological testing will help identify the number of past infections, which can help epidemiologists better understand the true burden of disease to model viral dynamics. sars-cov- testing is also important for identifying potential convalescent plasma donors for clinical trials. studies are currently underway where patients who have recovered from sars-cov- and have detectable antibodies against sars-cov- can donate plasma, which can then be transfused to patients who are currently critically ill with covid- . theoretically, the neutralizing antibodies against sars-cov- present in the plasma will help patients currently infected overcome the illness. serologic testing to identify anti-sars-cov- antibodies are now part of the donor work-up to determine eligibility for clinical trials. at some institutions in new york city, potential donors also require rt-pcr testing to determine if they are still actively shedding virus and, therefore, contagious. there is now one antigen detection assay available from quidel which uses a lateral flow clinical laboratory improvement amendment (clia) of sars-cov and sars-cov- . information provided by the manufacturer in the package insert indicates an % concordance when compared to pcr. historically, antigen detection kits for viruses have not performed well so the utility for sars cov- remains to be determined. such tests are used routinely for other viruses -hiv p antigen as part of th and th generation hiv tests, and also for hepatitis b surface antigen [ ] . laboratories regulated by clinical laboratory improvement amendment (clia) were able to get eua for laboratory developed tests (ldt's) either directly from the fda or, the wadsworth center of the new york state department of health, as in the case of several laboratories in new york. the eua route permitted the laboratories to implement the ldt's for routine clinical diagnostics. unfortunately, in spite of these sanctions, the inability to provide broad diagnostic testing, was widely seen as a failing effort to contain the virus. this setback of optimal testing in a crisis, was largely due to lack of a national laboratory testing strategic plan that brings together the major players in diagnostic testing, including public health, clinical / hospital-based, and commercial laboratories. clinical hospital-based laboratories play a major role in identification and containment of infectious threats and a coordinated laboratory network would likely be more effective at damage control earlier in pandemics such as the current one [ ] . in summary, testing has been critical to understanding and managing the sars-cov- pandemic. while both molecular and serological tests provide meaningful data for treating patients with sars-cov- , each methodology has a different clinical utility. as we move forward, clinical laboratories will continue to be on the forefront of combating this pandemic by developing new assays and implementing increased testing capabilities to meet the high-volume demands necessitated by this pandemic. a concerted rather than isolated effort may be the best approach to accomplish mass-scale testing. world health organization coronavirus disease (covid- ) pandemic impact of viral multiplex real-time pcr on management of respiratory tract infection: a retrospective cohort study. pneumonia (nathan) coronavirus and the race to distribute reliable diagnostics new york state department of health covid- tracker food and drug administration emergency use authorizations interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease comparison between saliva and nasopharyngeal swab specimens for detection of respiratory viruses by multiplex reverse transcription-pcr patient-collected tongue, nasal, and midturbinate swabs for sars-cov- yield equivalent sensitivity to health care worker collected nasopharyngeal swabs variation in false-negative rate of reverse transcriptase polymerase chain reaction-based sars-cov- tests by time since exposure virological assessment of hospitalized patients with covid- laboratory diagnosis of emerging human coronavirus infections -the state of the art evaluation of transport media and specimen transport conditions for the detection of sars-cov- using real time reverse transcription pcr development of reverse transcription loop-mediated isothermal amplification assays targeting severe acute respiratory syndrome coronavirus point-of-care testing for covid- using sherlock diagnostics comparison of cepheid xpert xpress and abbott id now to roche cobas for the rapid detection of sars-cov- comparison of abbott id now and abbott m methods for the detection of sars-cov- from nasopharyngeal and nasal swabs from symptomatic patients evaluation of the covid id now eua assay clinical evaluation of three sample-to-answer platforms for the detection of sars-cov- performance of the rapid nucleic acid amplification by abbott id now covid- in nasopharyngeal swabs transported in viral media and dry nasal swabs, in a new york city academic institution food and drug administration beware of fraudulent coronavirus tests, vaccines and treatments antibody responses to sars-cov- in patients of novel coronavirus disease temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by sars-cov- : an observational cohort study immune responses and pathogenesis of sars-cov- during an outbreak in iran: comparison with sars and mers epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study. the lancet p revisited: a landscape review of antigen detection for early hiv diagnosis laboratories and pandemic preparedness: a framework for collaboration and oversight figure : number of individuals tested and number of positive cases from figure : schematic of the antibody response to sars cov- why do we need antibody tests for covid- ? available at key: cord- -tluc ck authors: kuiken, thijs; breitbart, mya; beer, martin; grund, christian; höper, dirk; van den hoogen, bernadette; kerkhoffs, jean-louis h; kroes, aloys c m; rosario, karyna; van run, peter; schwarz, matthias; svraka, sanela; teifke, jens; koopmans, marion title: zoonotic infection with pigeon paramyxovirus type linked to fatal pneumonia date: - - journal: j infect dis doi: . /infdis/jiy sha: doc_id: cord_uid: tluc ck the characteristics and risk factors of pigeon paramyxovirus type (ppmv- ) infection in humans are poorly known. we performed virological, pathological, and epidemiological analyses of a dutch case, and compared the results with those of a us case. both infections occurred in transplant patients under immunosuppressive therapy and caused fatal respiratory failure. both virus isolates clustered with ppmv- , which has pigeons and doves as reservoir. experimentally inoculated pigeons became infected and transmitted the virus to naive pigeons. both patients were likely infected by contact with infected pigeons or doves. given the large populations of feral pigeons with ppmv- infection in cities, increasing urbanization, and a higher proportion of immunocompromised individuals, the risk of severe human ppmv- infections may increase. we recommend testing for avian paramyxovirus type , including ppmv- , in respiratory disease cases where common respiratory pathogens cannot be identified. changes in socioeconomic, environmental, and ecological factors in recent decades are probably responsible for the significant increase of emerging infectious diseases, the majority of which are zoonotic [ ] . of particular concern are emerging respiratory viruses of the families orthomyxoviridae [ , ] , coronaviridae [ , ] , and paramyxoviridae [ , ] . the use of novel molecular techniques has made it possible to identify previously unsuspected or unknown viruses [ ] . however, it is important to assess the clinical and public health relevance of these viruses by determining their origin and establishing their impact in the human population. the impetus for the current study was the identification of a virus related to avian paramyxovirus type (apmv- ) from a fatal human case of unknown cause in the netherlands by viral metagenomics analysis [ ] . apmv- is classified in the genus avulavirus, family paramyxoviridae [ ] . infection with apmv- is mainly restricted to birds, but occasionally causes mild disease-usually transient conjunctivitis-in humans [ ] . so far, there is only one case report, from new york state, of a person who died with apmv- infection [ ] . in this study, we fully characterized the dutch clinical isolate of apmv- -like virus, determined its phylogenetic relationship to other apmv- strains, and correlated presence of this virus with lesions in tissues obtained from the patient at autopsy. we also examined virulence and excretion pattern of this virus in chickens and domestic pigeons. a -year-old woman with a history of multiple myeloma received an allogenic bone marrow transplant in september , following preparation with a nonmyeloablative regimen (cyclosporin) and while on antifungal therapy (intravenous itraconazole). she initially did well, but was hospitalized weeks after transplantation with symptoms of malaise, anorexia, fever, and abdominal complaints (including abdominal pain, diarrhea, and food intolerance). she lived in the country near to a city, but was not employed in agriculture, and there was no evidence of contact with animals in her clinical history. gastroscopic examination showed no abnormalities. infiltrative lesions in the thorax were detected by radiological and computed tomographic examinations, and there was progressive swelling of cervical lymph nodes. no pathogens were detected in bronchoalveolar lavage (bal) specimens (virus culture on hel, llc-mk , hep- , and human rhabdomyosarcoma cells; bacterial culture on blood agar, chocolate agar, columbia blood agar containing colistin and nalidixic acid, and sabouraud agar; cytological examination for bacteria, fungi, and pneumocystis carinii), and a biopsy of the peripheral right lower lung lobe was histologically normal. epstein-barr virus (ebv) antigen expression and lymphoproliferation were detected in a biopsy of the right jugular lymph node, and a blood sample was positive for ebv dna by polymerase chain reaction (pcr). reactivation of ebv and associated lymphoproliferation were treated successfully with rituximab (anti-cd ) and discontinuation of cyclosporin therapy, but other clinical signs remained. enteroscopic examination of the small intestine showed no abnormalities, and no pathogens were detected in fecal samples by bacterial culture. five weeks after hospitalization, the patient developed high fever and progressive worsening of respiratory signs. treatment with cotrimoxazole was initiated for suspected p. carinii infection, and with prednisone for suspected bronchiolitis obliterans organizing pneumonia or graft-vs-host disease of the lung. two weeks later, the patient developed respiratory failure. there was crepitation over both lung fields and bilateral, progressively expanding, blotchy infiltrates in the thorax by radiological examination. gram-negative, rod-shaped bacteria (pseudomonas species) were detected by microscopic examination of bal fluid, and treatment with ceftazidime and tobramycin was initiated. despite intubation and artificial respiration at increasing pressure, respiratory function deteriorated further and circulatory failure developed. artificial respiration was stopped after days, after which the patient died. autopsy was performed day after death. there were extensive areas of bronchopneumonia associated with pseudomonas species infection in both lungs by bacterial culture. in addition, there was marked diffuse alveolar damage, characterized by abundant hyaline membranes lining the alveolar septa. the mucosa of the colon ascendens was lined by a hemorrhagic exudate, but autolysis was too advanced to confirm or rule out graft-vs-host disease, and no satisfactory explanation was found for the abdominal complaints. in conclusion, the progressive respiratory failure was explained by severe diffuse alveolar damage of undetermined cause, and extensive bilateral bronchopneumonia caused by terminal pseudomonas species infection. as part of an in-depth investigation, archived cell culture samples with an unexplained cytopathic effect were subjected to metagenomic analysis as described previously [ ] . these samples included human rhabdomyosarcoma cells inoculated with a bal specimen collected in from the above patient. metagenomic analysis revealed the presence of short nucleotide fragments with homology to apmv- . to complete the genome of the clinical isolate, fragments obtained through whole transcriptome amplification were assembled against the apmv- genome with the highest similarity (supplementary methods). in brief, the assembly was performed using sequencher software (version . ; gene codes). because the whole-transcriptome amplification fragments did not overlap into a complete genome, the assembly was used to design primers for genome walking, pcr assays were performed with these primers, and products were sequenced. these efforts resulted in the genome completion of the dutch clinical virus isolate. nucleotide sequences were aligned with the clustal w program running within the bioedit software package, version . . [ ] . with the nucleotide sequence alignment, the best-fit model of nucleotide substitution was determined by jmodeltest [ ] . maximum-likelihood (ml) phylogenetic trees were generated using the gtr+Γ +i model of nucleotide substitution and the phyml package version . [ ] . the reliability of all phylogenetic groupings was determined through a bootstrap resampling analysis of a replicates with phyml. trees were visualized through the figtree program version . . (http://tree.bio.ed.ac. uk/software/figtree/) and rooted on the apmv- with the highest blast similarity in genbank (apmv- /nl/ / ). the following tissue biopsies and autopsy tissue specimens had been fixed in % neutral-buffered formalin and embedded in paraffin blocks: heart, lung, jugular lymph node, esophagus, thyroid gland, stomach, pancreas, liver, kidney, skin, diaphragm, and muscle. these specimens were used for detection of apmv- rna by real-time reverse-transcription pcr (rt-pcr), of apmv- antigen by immunoperoxidase method, and of histological lesions by hematoxylin and eosin stain (supplementary methods). chickens were inoculated intracerebrally with the dutch clinical virus isolate to determine the intracerebral pathogenicity index (supplementary methods). domestic pigeons were inoculated intratracheally with the dutch clinical virus isolate to determine infectivity and transmissibility, clinical signs, and pathological changes (supplementary methods). the sequence of the full-length genome of the dutch clinical virus isolate displayed % nucleotide sequence homology with an apmv- isolated from pigeons in belgium (apmv- / belgium/ - / ; jx ). phylogenetic analysis of fulllength genomic sequences of closely related apmv- isolates demonstrated that the dutch clinical isolate clustered among belgian and chinese avian strains in genotype vib/ ( figure ). viruses in this genotype are also called pigeon paramyxovirus type (ppmv- ), because pigeons and doves are the animal reservoir. therefore, the dutch clinical virus isolate was named human ppmv- (hppmv- /nl/ / ; accession number kj ). comparison of predicted amino acid sequences revealed that all of the hppmv- /nl/ / encoded proteins displayed > % identity with those of other ppmv- . in general, the fusion protein (f) cleavage site of medium/high virulent apmv- s contain the sequence rq(k/r)r*f , while those of low virulent apmv- s usually have the sequence (k/r) q(g/e)r*l . the cleavage site of hppmv- /nl/ / ( rqkr*f ) was consistent with a virulent pathotype, similar to that observed in all ppmv- ( r(q/k) kr*f ) [ ] [ ] [ ] . based on phylogenetic analysis of sequences of partial f protein sequences, ujvári et al identified sublineages of ppmv- (ie, apmv- genotype vib/ ) strains. these subgroups, designated iraqi (iq), early european (eu/ea), north american (na), with related avian paramyxovirus type (apmv- ) strains based on analysis of full-length genomes. assignment of apmv- genotypes (vib/ or vii) and sublineages (eure , eure , euea , or euea ) was based on the studies of ujvári et al [ ] and czegledi et al [ ] and the sequence comparison shown in table and recent european (eu/re), corresponded partly to the times of isolation and/or geographical origin [ ] . alignment of the f protein amino acid sequences from hppmv- /nl/ / with those of ujvári and others revealed that it had identical amino acids substitutions as isolates belonging to sublineage eur/re (table ) . no sequence information was available for this partial f protein sequence of the only other apmv- clinical isolate, from a fatal human case in new york state [ ] . the available partial sequence for this new york clinical virus isolate demonstrated the closest relationship with a ppmv- isolated from pigeons in new york in (kc . ), and clustering in sublineage vib/ na (data not shown). real-time rt-pcr analysis revealed the presence of high levels of ppmv- rna in the left and right lung ( table ) . lower levels were detected in liver, kidney, and bone marrow, while the remaining tissues tested negative. immunohistochemistry analysis revealed the expression of ppmv- antigen, visible as red-brown granular staining, in the same tissues that tested positive with real-time rt-pcr ( table ). the exact localization of these granules was not clear, although some aggregates of granules appeared to be located in the cytoplasm of degenerate cells (figure ). ppmv- antigen expression was present in the positive control tissue and absent in the isotype control and negative control tissues. histopathological examination demonstrated that ppmv- antigen-expressing sections of lung had diffuse alveolar damage, characterized by loss of alveolar epithelium, rare hypertrophic type ii pneumocytes, widened alveolar septa, and fibrin thrombi in alveolar capillaries ( figure ). no histological lesions were apparent in other tissues that expressed ppmv- antigen, or in ppmv- -negative tissues. based on intracerebral inoculation into -day-old chickens, the intracerebral pathogenicity index of hppmv- /nl/ / was . (supplementary table ). this corresponds with a lentogenic pathotype. in pigeons, all intratracheally inoculated animals developed a productive infection, with shedding from the pharynx between and dpi, and from the cloaca between and dpi (supplementary figure ) . virus was transmitted to of the naive pigeons. none of the pigeons displayed clinical signs at any time point during the -week observation period. no gross lesions were observed in any pigeons at autopsy at dpi. however, histopathological analysis showed that all intratracheally inoculated pigeons plus the infected naive pigeon had diffuse interstitial nonpurulent nephritis, which was absent in negative control pigeons from the same flock (supplementary figure ) . also, inoculated pigeon had multifocal nonpurulent pancreatitis. real-time rt-pcr analysis revealed that hppmv- /nl/ / was present in the kidney sample of inoculated pigeons with nephritis, and in the pancreas sample of inoculated pigeons, including the with pancreatitis (supplementary figure ) . discussion we diagnosed ppmv- infection as the cause of diffuse alveolar damage in the dutch female patient, based on colocalization of ppmv- antigen, high loads of ppmv- rna, and characteristic histological lesions in autopsy specimens ( figure and table ). the ppmv- -associated diffuse alveolar damage was exacerbated by bronchopneumonia due to pseudomonas species infection, probably from intravenous catheterization. the combination of these pulmonary diseases likely explains the severe respiratory failure leading to the death of this immunosuppressed patient. it is rare to diagnose ppmv- infection as the cause of severe respiratory disease in humans. to our knowledge, the only other known case was reported by the new york state department of health in [ ] . it is not clear whether this paucity of reports is because the disease is rare or because apmv- , including ppmv- , is not suspected in such cases. we suggest that apmv- , including ppmv- , should be included in the differential diagnosis of cases of respiratory disease that test negative for more common respiratory pathogens. samples could be tested by various molecular methods, such as a family-wide rt-pcr assay for paramyxoviruses or metagenomics approaches [ , ] . when they became infected with ppmv- , the dutch and new york patients were receiving immunosuppressive therapy to improve the success of peripheral blood stem cell or bone marrow transplantation. there is an increase in the proportion of immunocompromised people in the population [ ] . as these immunocompromised people are at high risk of severe disease from other opportunistic infections [ ] , they also may be at risk of severe disease from infection with apmv- , including ppmv- . ppmv- appears to target the lower respiratory tract epithelium in humans. this is based on the demonstration of ppmv- antigen expression in the alveolar epithelium of autopsy lung samples from both human cases (figure ) [ ] . the tissue tropism of ppmv- in these human cases resembles that of other emerging zoonotic respiratory viruses-h n influenza virus and the severe acute respiratory syndrome and middle east respiratory syndrome coronaviruses-that also target the lower respiratory tract [ , [ ] [ ] [ ] . there was evidence of extrarespiratory spread of ppmv- in the dutch case. this was based on evidence of ppmv- infection in liver, kidney, and bone marrow ( table ). this is consistent with the new york case, where evidence of ppmv- infection in feces and urine also suggested extrarespiratory pigeon paramyxovirus-linked pneumonia • jid : ( october) • table spread [ ] . the immunosuppressive state of the dutch and new york patients may have allowed spread of ppmv- beyond the respiratory tract. pigeons and doves are the animal reservoir of ppmv- ( figure and table ). in europe, these viruses are circulating predominantly in domestic pigeons (columba livia domestica) or their wild relatives (rock pigeons, c. livia), and other members of the family columbidae, especially eurasian collared doves (streptopelia decaocto) and european turtle doves (streptopelia turtur) [ ] . the tropism of hppmv- / nl/ / for the kidney and pancreas of experimentally infected pigeons ( supplementary figures and ) matches the tissue tropism of ppmv- in naturally infected pigeons [ ] . the low pathogenicity of this isolate in chickens fits with the phenotype of other ppmv- strains [ ] . the number of feral pigeons-free-living birds that have descended from domestic pigeons-in european and north american cities increased substantially from the s to the s as a result of changes in agricultural practices and the rapid human population increase after world war ii. feral pigeon numbers then stabilized, likely due to reaching the carrying capacity of the urban environment. however, population growth of feral pigeons is still likely to occur in recently colonized cities and at the newly built outskirts of cities [ ] . first reported in italy in [ ] , ppmv- subsequently spread across europe and has become endemic in feral pigeons, with regular spread to wild pigeons and doves [ ] . in north america, ppmv- was introduced in the s and now is maintained endemically in pigeons and doves [ ] , including the eurasian collared dove [ , ] . this invasive species, first reported in florida in the s, has rapidly spread across most of north america (http://www.audubon.org/field-guide/bird/ eurasian-collared-dove), and could facilitate virus dispersal throughout north america [ , ] . the clinical histories of the dutch and new york cases do not readily explain how they became infected. the dutch patient lived in a rural area near a city, but was not employed in agriculture, and there was no evidence of contact with animals (this study). the new york patient was an urban dweller, but it is unknown whether he had pets or was exposed to birds in other settings [ ] . based on phylogenetic analysis of the viruses, the most probable route of transmission was contact with infected pigeons or doves. ppmv- is environmentally stable in bird feces and can be spread by direct contact or by windborne dust [ ] . the route of transmission of other zoonotic pathogens from pigeons to humans may be instructive. five pathogen species (chlamydia psittaci, histoplasma capsulatum, aspergillus species, candida parapsilosis, and cryptococcus neoformans) have been reported to be routinely transmitted from feral pigeons to people [ ] , mostly by inhalation of airborne excreta, including dried feces, ocular discharges, and crop milk. contact was sometimes brief, and patients did not always recall any bone marrow (n = ) + heart, esophagus, stomach, pancreas, right kidney, skin, diaphragm, and muscle tested negative for ppmv- rna by real-time reverse-transcription polymerase chain reaction and for ppmv- antigen by immunohistochemistry; lung biopsy and lymph node biopsy tested negative for ppmv- antigen by immunohistochemistry. abbreviations: +, rare positive granules; ++, occasional positive granules; ct, cycle threshold; ppmv- , pigeon paramyxovirus type . encounters with birds. it is relevant for these ppmv- cases that the risk of pigeon-associated diseases-chlamydiosis and cryptococcosis-was largely a function of the immune status of patients, rather than contact with infected birds [ , ] . close contact between feral pigeons and humans commonly occurs in squares, public gardens, parks, markets, and railway stations in urban areas [ ] . therefore, people in urban areas are likely to have a higher rate of contact with feral pigeons than in rural areas. the proportion of the global human population living in urban areas is increasing. in , % of the world's population lived in urban areas; this increased to % in , and by , % of the world's population is projected to be urban [ ] . this suggests that the number of people at risk of contracting zoonotic infections, including ppmv- , from feral pigeons will increase in coming decades. the combination of the above factors-large populations of feral pigeons with endemic ppmv- infection, increasing urbanization, and a higher proportion of immunocompromised individuals-may increase the risk of severe human cases of ppmv- infection. supplementary materials are available at the journal of infectious diseases online. consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. global trends in emerging infectious diseases adaptive pathways of zoonotic influenza viruses: from exposure to establishment in humans limited airborne transmission of h n influenza a virus between ferrets the severe acute respiratory syndrome cross host transmission in the emergence of mers coronavirus nipah virus: transmission of a zoonotic paramyxovirus hendra virus ecology and transmission metagenomic sequencing for virus identification in a public-health setting fields virology. philadelphia: wolters kluwer avian influenza and newcastle disease isolation of avian paramyxovirus from a patient with a lethal case of pneumonia bioedit: a user-friendly biological sequence alignment editor and analysis program for windows / /nt jmodeltest: phylogenetic model averaging a simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood newcastle disease in the european union phylogenetic analysis reveals extensive evolution of avian paramyxovirus type strains of pigeons (columba livia) and suggests multiple species transmission virulence of pigeon paramyxovirus type does not always correlate with the cleavability of its fusion protein a family-wide rt-pcr assay for detection of paramyxoviruses and application to a large-scale surveillance study virome capture sequencing enables sensitive viral diagnosis and comprehensive virome analysis pathogenesis of middle east respiratory syndrome coronavirus epidemiology of invasive mycoses in north america newly discovered coronavirus as the primary cause of severe acute respiratory syndrome pathology of human influenza revisited pathogenesis of influenza-induced acute respiratory distress syndrome avian paramyxovirus type infections in racing pigeons in california. i. clinical signs, pathology, and serology partial characterisation of five cloned viruses differing in pathogenicity, obtained from a single isolate of pigeon paramyxovirus type (ppmv- ) following passage in fowls' eggs feral pigeons: problems, dynamics and control methods. integrated pest management and pest control: current and future tactics successful establishment and global dispersal of genotype vi avian paramyxovirus serotype after cross species transmission expansion of an exotic species and concomitant disease outbreaks: pigeon paramyxovirus in free-ranging eurasian collared doves newcastle disease: methods of spread health hazards posed by feral pigeons chlamydial infections in feral pigeons in europe: review of data and focus on public health implications world urbanization prospects: revision, highlights (st/esa/ser. a/ ) the occurrence of five major newcastle disease virus genotypes we thank the department of pathology, leiden university medical center, the netherlands, for providing biopsies and autopsy specimens from the dutch patient.financial support. this work was supported by european fp programme antigone (anticipating the global onset of novel epidemics, project number ) and by the european commission h programme under contract number (www.compare_europe.eu).potential conflicts of interest. all authors: no reported conflicts of interest. all authors have submitted the icmje form for disclosure of potential conflicts of interest. conflicts that the editors consider relevant to the content of the manuscript have been disclosed. key: cord- -oqe rcbu authors: laufer, daniel title: academics engaging through the media—insights from creating a monthly column on crisis management date: - - journal: public relat rev doi: . /j.pubrev. . sha: doc_id: cord_uid: oqe rcbu universities increasingly expect academics to engage with external stakeholders. this includes providing media commentary. in this article i describe my experience writing a monthly column on crisis management in the new zealand herald, the most widely read newspaper in new zealand with an average daily readership of over , people (new zealand herald, ). the article also describes the benefits of writing a newspaper column including educating the public about issues relating to crisis management such as managing covid- , creating a platform for enhancing collaboration between academics and public relations firms, and enhancing the reputation of both the academic and university. this article will benefit academics in the field of public relations who are interested in writing a newspaper column to engage through the media. research and teaching-oriented universities increasingly expect academics to engage with external stakeholders. these stakeholders include companies, the government and the general public. leading academic organizations also recognize the need for increased external engagement. for example, the american political science association created a task force to discuss how to generate effective engagement (mcmurtrie, ) . an important type of engagement activity for academics is commentary in the media which is a way to educate the public about an important topic related to a scholar's area of expertise. an academic's perspective is viewed by many in the public as an informed and relatively unbiased opinion compared to other commentators. this is especially important during the covid- crisis when trust in the government in many countries is in decline, and the public is looking for credible sources of information. whereas writing op-eds, speeches and granting media interviews are beneficial for both the academic and university, i believe other types of activities are more reputation enhancing. for example, writing a column in one's area of expertise for an influential media outlet enables academics to have a longer-term impact that goes beyond occasional commentary. in this article i describe my experience writing a regular column about crisis management for the new zealand herald, the most widely read newspaper in new zealand with an average daily readership of over , people (new zealand herald, ) . in the following sections i describe the benefits of writing a newspaper column, and my experience writing a column from to . a key difference between writing a regular column and providing occasional commentary is control over content. when being interviewed for a story, an academic typically spends a considerable amount of time speaking with reporters and answering questions through email correspondence. despite these lengthy and in-depth conversations with reporters, in most cases when the news articles are published, only select quotes from the academic expert's commentary are included. unlike providing occasional commentary for the media, writing a regular column for a newspaper provides a much greater level of control and autonomy for an academic. since i started writing my monthly column on crisis management in early , i've always chosen the topic of the column, as well as the content included in the − , word monthly column. my column has appeared times in the newspaper since i was hired to write the column, and the editor has made only minor editing changes on rare occasions before publishing the column. having greater control over the content minimizes the risk of being misquoted or taken out of context. this is a major concern of academics when dealing with the media. in many situations journalists will choose the quotes they prefer to use, and this may distort the views of academics in a published newspaper article or a news clip on tv or the https://doi.org/ . /j.pubrev. . e-mail address: dan.laufer@vuw.ac.nz. radio. a good example of this is a tv interview with cynthia miller-idriss a professor of education and sociology at american university. she was interviewed on nbc's today show in the usa for a segment on how white nationalists were trying to infiltrate college campuses. the sound bite used by the today show featured professor miller-idriss calling a white-nationalist group "smart" and "savvy". after the interview aired, professor miller-idriss mentioned that her comments were taken out of context and did not include "the context of my larger points about why the mainstreaming of extremism in the united states is so dangerous" (miller-idriss, ). commentary in the media enhances both the reputation of the academic and the university. the academic benefits from commentary in the media because the general public learns more about the expertise of the scholar, which enhances the reputation of the scholar as an expert in his or her area of specialization. this can create opportunities for the academic including invitations for giving presentations, membership on advisory boards, and consulting projects (miller-idriss, ) . in addition, the university benefits because it is viewed by the public as a prestigious institution employing scholars highly sought after by the media for commentary on important issues related to their areas of expertise. this can influence prospective students in deciding whether to apply for programs at a university, or alumni in donating to the university. according to orr ( ) "universities are now competitive businesses as much as spaces for advancing knowledge. universities market themselves as brands, hence media attention is one way university bureaucrats measure success". writing a column in a newspaper can enhance the reputation of an academic and a university even more than occasional commentary in the media. the frequency of exposure to the public through the publication of a column can strengthen perceptions of the public regarding an academic's standing in his or her area of expertise. in addition, the academic's name and university is typically featured more prominently in a column when compared with being quoted in the media. in order to maximize the chances of convincing a newspaper to launch a new column, it is important to demonstrate that an academic has the ability to write a regular column. an effective way to show that an academic can be successful as a columnist is to prepare a portfolio of previous media commentary. when in addition to the importance of prior experience writing commentary in the area of crisis management for a well-known global media outlet, experience with media commentary in new zealand was also important. my commentary for radio new zealand about a product tampering crisis involving imported strawberries from australia (laufer, ) , and an interview about my research on tv 's q + a, the leading weekly news program on tv in new zealand, played an important role in the new zealand herald's decision to hire me as a columnist. finally, beyond demonstrating relevant experience, an academic also needs to convince the newspaper that its audience will be interested in reading a new column. in my case the new zealand herald had never previously published a regular column focused exclusively on crisis management. in pitching the idea, i emphasized the success of the "crisis of the week" column in the wall street journal, as well as the interest of major media outlets in new zealand for commentary on topics related to crisis management. this was compelling support for the potential of the new column in attracting interest among the newspaper's readers. my efforts to convince the new zealand herald to launch a new column on crisis management were successful, and i received a oneyear contract to write a monthly column in ( − , words). due to the success of the column, the contract was extended for another year in . in determining the topics and content to include in my column, there were a number of factors that influenced my decision: in writing my column, i wanted to educate the public about topics related to all three phases of a crisis (for a list of topics in my column, see appendix a). it is worth noting that most research published in the area of crisis management focuses on the crisis phase (coombs & laufer, ) , and the media also tends to focus on issues around managing a crisis. despite the importance of knowing how to respond to a crisis when it happens, how to prevent a crisis from occurring (precrisis phase), and how to learn from a crisis (post-crisis phase) are also important topics in crisis management which i wanted to incorporate in my column. in order to emphasize the importance of crisis prevention, i decided to write about a topic related to the pre-crisis phase in my inaugural column. my focus in the column was on crisis contagion, or how a crisis occurring in one organization can spillover to others (laufer & wang, ) . the column described ways a company can assess the risk of crisis contagion, and how it can manage the risk. an example of a topic related to managing a crisis in my column was a discussion about whether to use a ceo as a spokesperson during a crisis (laufer, ) . this topic is of great interest to companies who need to decide the best way to communicate their message during a crisis. should they use the ceo, or perhaps another spokesperson may be more effective in communicating during the crisis? the column discussed several factors to consider in deciding whether to use the ceo as a spokesperson during a crisis. another topic related to managing a crisis in my column involved carnival cruise's response to the covid- crisis on its cruise ships. in the column, the company was criticized for its poor response. according to claudia macdonald, managing director, mango communications nz, who provided commentary in my column "their lack of communication to date is not helping them repudiate an already shaky health reputation. the president of princess cruises only spoke this week for the first timemore than a month after the first incident". finally, my column also covered topics related to the post-crisis phase. for example, i discussed conducting an investigation after a crisis. what increases the likelihood that learning will take place after the findings from an investigation are published? in the column i discuss factors that enhance the credibility of an investigation, and the likelihood that recommendations from an investigation will be accepted by stakeholders. when deciding on topics for my column, my research provides me with a lot of useful ideas. these included writing about crisis contagion public relations review xxx (xxxx) xxxx (laufer & wang, ) , how crisis management in china differs from the west (wang & laufer, ) when to use the ceo as a spokesperson during a crisis (einwiller, laufer, & ruppel, ; laufer, garrett, & ning, ) and how to manage customer rage (gregoire, laufer, & tripp, ) . however, in deciding whether to focus on my research topics for my column, an important consideration is my target audience. is my research of interest to the general public, or is it primarily of interest to an academic audience? for example, an article about the usefulness of a scale would be of great interest to academics, however it would not be a good topic for the column. in addition to my research, i incorporate information from other sources as well, including government officials. for example, i interviewed a senior government official from the ministry of business, innovation and employment in new zealand for a column about managing product recalls. during the interview, i asked the senior product safety analyst about the most common mistakes companies make in new zealand during a product recall. this type of information is of great interest to the readers of the herald, and it was included in the column. as previously mentioned, the relevance of a topic to the newspaper's readers is an important consideration in choosing the topic for the column. an important issue related to relevance is whether the audience is familiar with the organizations involved in the crises. as a result, i include examples of well-known new zealand companies that have experienced crises in my column. for example, when i wrote my column on consumer outrage, i discussed a crisis involving burgerfuel, a well-known fast-food restaurant chain in new zealand. the crisis occurred when an employee at a burgerfuel franchise in auckland used blackface to promote a new jamaican burger launched by the company. in the same column i also describe the outrage directed towards air new zealand, the country's national carrier, after the christchurch mosque shootings in march . the airline raised its prices after the shooting due to the increased demand in flights to christchurch. despite the importance of including local content in the column, i also believe it is important to discuss global topics. new zealand is a country that relies heavily on international trade, and readers of the herald are interested in news from overseas. in one of my columns i wrote about how crisis management in china differs from the west. china is new zealand's largest trading partner, and there is also a free agreement between new zealand and china. finally, covid- is an example of a crisis with a significant impact both globally and domestically. the crisis has dominated the news over the past few months, and my column has covered covid- three times. there is enormous interest in the topic, and no other crisis has been covered as frequently in my column. covid- was also the first topic that was covered under the new format of the column involving an exchange of views between academics and practitioners. in the next section, i will discuss the new format of the column. after my contract as a columnist for the herald was renewed in , i decided to make changes to the column. the newspaper was pleased with the column, however i felt that through changes to the format i could achieve another important objective, creating a platform for an exchange of views between academics and practitioners. collaboration between academics and practitioners has long been identified as an important objective in the field of public relations. for example, the commission on public relations education (cpre) states that increasing collaboration between educators and practitioners advances excellence in public relations education and practice throughout the world (http://www.commissionpred.org/). an important prerequisite to collaboration is creating a greater understanding of the different ways practitioners and academics view issues. before considering collaboration, both practitioners and academics need to assess the potential benefits of collaboration. through the mutual exchange of ideas in the column, practitioners can assess the potential benefit of academics' ideas for improving their practice, and academics can assess the potential for research collaboration and improvements in teaching by incorporating the practitioner's perspective. newspaper readers of the column also benefit from this exchange of views by getting different perspectives on crisis management. in redesigning the column, i incorporated the approach taken by the wall street journal with their "crisis of the week" column by creating a panel of experts. as part of the new format for the column, i decided to incorporate commentary from both a practitioner and an academic on how an organization or individual performed during a crisis. both experts would have up to words to give their perspective. the response to the new format of the column has been overwhelmingly positive from both academics and practitioners. academic experts in crisis management from most of the major universities in new zealand have agreed to provide commentary for the column. similarly, most of the leading public relations firms in new zealand with expertise in crisis management have also agreed to provide commentary. in total, i have a pool of people on my panel of experts comprising of both academics and practitioners. each month i choose two different experts to provide commentary for the column. the herald has already published the column three times with the new format. with covid- dominating the news, i decided to focus on how individuals and companies are managing the pandemic. the column has focused on the prime minister of new zealand's response to the crisis, how air new zealand is managing covid- , and how carnival cruises' is managing the pandemic. feedback from the new format has been very encouraging. for example, my column about the prime minister of new zealand's response to covid- was included on an influential list of recommended news articles by one of the leading online news outlets in new zealand (newsroom, ) . writing a newspaper column is a very fulfilling experience that can greatly benefit academics and universities. despite the considerable amount of time involved in writing a column, i believe the benefits greatly outweigh the costs. in writing my column on crisis management, in addition to the benefits to academics and universities, i believe that the field of public relations can benefit as well through the potential for future increased collaboration between academics and practitioners. the public also benefits through exposure to a diversity of views expressed on topics related to crisis management by leading experts from both academia and public relations firms. writing a column has enabled me to share my expertise with the general public, which has resulted in a number of opportunities. these include receiving invitations to give presentations at high profile industry events and to teach webinars. it is worth noting that one event has been especially gratifying. as a result of the column, i was invited to give a presentation to high school teachers in auckland to discuss how the column can be used to teach their students about crisis management. i believe teaching crisis management in high schools will increase the demand for crisis management courses at universities in the future. my university has also benefited from the column. as part of my contract with the new zealand herald, my university has permission to post the column on its website one month after it is published in the newspaper. by sharing the column with its stakeholders, the university can highlight that its faculty provide commentary on a regular basis in their area of expertise in leading media outlets. this enhances the reputation of the university. creating a platform through the column that incorporates the views of both academics and practitioners can also play an important role in bridging the gap between these groups. in many cases, academics and practitioners are not familiar with each other's work. by including commentary in the column from both groups, this increases the chances that they will become more familiar with each other's views and ideas. to facilitate this, i email a copy of the column to my panel of experts after it is published, so they can read the commentary of the academic and practitioner. finally, the public also benefits from a diversity of views. this is especially important during times of crises such as covid- when there is a need for reliable information from credible sources. by presenting the views of leading experts from academia and public relations firms, the public learns about important concepts in crisis management. for example, in his commentary on the response of air new zealand to covid- (new zealand herald, ) , dr. chris galloway from massey university mentioned that "this is the time when lessons need to be absorbed, new operational procedures and structures introduced, and reputations rebuilt where damage has occurred". neil green, chief executive, senate shj, a leading public relations firm in new zealand, also provided useful commentary in the same column: "clarity of communication and calmness under pressure are highly regarded leadership attributes and foran (ceo of air new zealand) has consistently demonstrated both, earning respect and goodwill from staff, customers, shareholders and other stakeholders". after reading the column, readers gain a better understanding of best practices when dealing with a pandemic. this is of great value to the public and represents an important contribution in the area of engagement. appendix a. list of topics in column on crisis management in the new zealand herald ( - ) • how companies can protect themselves from crisis contagion. • beware of judging during uncertain times. • should the ceo of a company be a spokesperson during a crisis? • what causes consumer outrage, and how can companies prevent it from happening? • can celebrity endorser crisis spread to companies? • when trouble strikes, investigate. • how to avoid costly mistakes when managing a product recall. • firms losing victim status in data hacks. • what foreign companies can learn from past crises. • crisis management in the era of social media. • crisis management in china: how it differs from the west. • think long term before going on a limb: weigh the risks before you take a stand that can later prove controversial. • how has prime minister jacinda ardern been managing the coronavirus crisis (includes expert commentary from academic and practitioner). • covid- coronavirus: air new zealand's response (includes expert commentary from academic and practitioner). • carnival cruises' response to covid- (includes expert commentary from academic and practitioner). global crisis management -current research and future directions believe me, i am one of you! the role of common group affiliation in crisis communication a comprehensive model of customer direct and indirect revenge: understanding the effects of perceived greed and customer power should ceos of multinationals be spokespersons during an overseas product harm crisis strawberry crisis: how nz growers can prevent "crisis contagion guilty by association -the risk of crisis contagion examining the effectiveness of the ceo as a spokesperson during a product harm crisis: insights from china and south korea political scientists propose new ways to engage policy makers and the public lessons i learned -and you can, too -from my 'today' show appearance nz herald defies trends with soaring readership covid- coronavirus: air new zealand's response. retrieved from media monitoring -bernard's pick of the links-mar academics and media in australia. retrieved from:the university of queensland tc beirne school of law legal studies research papers series how does crisis management in china differ from the west? -a review of the literature and directions for future research key: cord- -xcf jmqp authors: rickards, c. g.; kilpatrick, a. m. title: age-stratified sars-cov- infection fatality rates in new york city estimated from serological data date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: xcf jmqp importance: covid- has killed hundreds of thousands of people in the us and > million globally. estimating the age-specific infection fatality rate (ifr) of sars-cov- for different populations is crucial for assessing the fatality of covid- and for appropriately allocating limited vaccine supplies to minimize mortality. objective: to estimate ifrs for covid- in new york city and compare them to ifrs from other countries. design, setting, participants: we used data from a published serosurvey of individuals years or older conducted april - , with time series of covid- confirmed cases and deaths for five age-classes from the new york city department of health and mental hygiene. we inferred age-specific ifrs using a bayesian framework that accounted for the distribution of delay between infection and seroconversion and infection and death. main outcome and measure: infection fatality rate. results: we found that ifrs increased approximately -fold with age, with a nearly linear increase on a log scale, from . % ( . %- . %) in - year olds to . % ( . %- . %) in individuals and older. new york city ifrs were higher for - year olds and - year olds ( . %; . %- . %) than spanish, english, and swiss populations, but ifrs for + year olds were lower than for english populations and similar to spanish and swiss populations. conclusions and relevance: these results suggest that the age-specific fatality of covid- differs among developed countries and raises questions about factors underlying these differences. covid- has killed hundreds of thousands of people in the us and > million globally. the infection fatality rate (ifr)or the chance of dying after becoming infectedof sars-cov- is a crucial metric for understanding disease severity. it has been the subject of substantial controversy, in part due to differences between the symptomatic or case fatality rate (cfr) and the infection fatality rate, and also due to differences between naïve estimates of cfr calculated from the ratio of deaths divided by cases and estimates of cfr that account for the delays between infection, case detection and death , . accurately estimating the ifr requires estimates of the number of infections at a point of in time and deaths that result from these infections which occur after a substantial, and highly variable, delay (mean . d; % ci . , . ; ). this makes simplistic calculations of ifr problematic when the incidence of infection is changing over time. previous analyses have shown enormous variation in ifr with age , - which indicates that accurate age-specific ifrs are needed to allocate limited supplies of vaccines to meet a goal of minimizing mortality from covid- . the most accurate approach for estimating age-specific ifrs is a large-scale serosurvey in a population where substantial mortality due to covid- has occurred , , because deaths in younger age groups are relatively rare . substantial differences in age-specific covid- ifrs are apparent in estimates from spain and england , indicating the need for additional ifr estimates from other hard-hit populations. we used data from a seroprevalence study conducted in new york city in the waning period of the spring epidemic and publicly available death records to estimate age-specific ifrs for the new york city population. we estimated infection fatality rates (ifrs) using data from new york city from a serological survey and confirmed covid- cases and deaths recorded by the new york city department of health and mental hygiene (https://www .nyc.gov/site/doh/covid/covid- -dataarchive.page). the serosurvey occurred on days over a -day period (april - ) two-weeks after the peak in covid- cases (fig ) . individuals for the serological survey were recruited at grocery stores without prior advertisement to reduce bias and increase randomization . daily case counts and number of deaths were obtained from the new york city department of health and mental hygiene archive webpage for the dates / / to / / (https://www .nyc.gov/site/doh/covid/covid- -data-archive.page). we estimated ifrs using a previously established bayesian statistical framework which combines seroprevalence estimates (including uncertainty) with time series of cases and deaths to estimate the number infected and the fraction dying over time using estimates (log-normal distributions) of the delays between infection, symptom onset, becoming a case, seroconversion, and death . this approach estimates the cumulative number of infected people at the time of the seroprevalence study and the fraction of those infected that go on to die. we calculated three age-specific estimates of ifrs to address mismatches in age-classes between deaths and seroprevalences and to consider both confirmed and probably covid- deaths (see supplemental materials: methods for details). we compared the ifr estimates for new york city to two other age-specific estimates . we show ifrs for england and geneva, switzerland that include care home resident deaths because the new york city deaths also include care home deaths (ifrs from spain excluded care home deaths and did not indicate their distribution among age categories). finally, we show ifrs for both confirmed covid- deaths and excess all-cause deaths for the two studies that included these estimates (ward et al. and pastor-barriuso et a. ). the serosurvey in new york city took place in late april, in the latter third of the initial epidemic, when new cases per day had fallen to approximately half of the peak (fig ) . at this point . % of the population was seropositive, and an estimated . million infections had occurred . due to the delay between infections and deaths, deaths from infections detected in the serosurvey extended into late may (fig ) . by may there were nearly , confirmed covid- deaths, and nearly , probable covid- deaths. the age-specific ifr for sars-cov- in new york city increased with age approximately -fold from . % in - to . % in + year-olds, in the raw analysis where we assumed equal seroprevalence for all subgroup age-classes ( - , - , +) within the + age-class (table ). in the adjusted analysis where used fine-scale age-specific seroprevalence data from spain to estimate seroprevalence of - year-olds and variation within the + age class, the ifr increased from . % for - year-olds, or roughly fatalities per , infected individuals to . % in + year-olds (table ) . including probable covid- deaths increased ifrs - % across the five age classes (table s ). the age-specific ifrs from new york city for the - and - age classes were higher (with non-overlapping % confidence intervals) than corresponding ifrs for england, geneva, france and spain, but had overlapping confidence intervals and were similar to estimates for china (figs. , s ). in contrast, the ifrs for the oldest two age classes, - and + were lower (with non-overlapping % cis) than ifrs from england, but had overlapping confidence intervals and were similar to corresponding ifrs from geneva, france, spain and china (figs , s ). the ifrs in new york city were higher for the two younger age classes ( - , - ), which accounted for % of the , deaths (table ) , than all three other studies based on large-scale serosurveys (geneva, spain and england). this may have been due to a higher prevalence of pre-existing conditions in these age-groups than in other populations; % and % of covid- deaths in these two age groups had pre-existing conditions (diabetes, lung disease, cancer, immunodeficiency, heart disease, hypertension, asthma, kidney disease, gi/liver disease, or obesity). in contrast, ifrs for the two older age classes were very similar to estimates from most other countries despite % and % of these deaths also having preexisting conditions. two other factors that influenced both ifrs or exposure to sars-cov- in previous studies are sex and race/ethnicity , , . although neither seroprevalence nor daily age-specific covid- deaths by sex and race/ethnicity were publicly available, crude calculations can be made assuming that differences in exposure and death between ages were consistent among . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . sexes and races/ethnicities. there were % more deaths in new york city in men than women, whereas seroprevalence was only . % higher in men than women , suggesting that ifrs for men were, on average across ages, % lower. this is a smaller sex difference than estimated for spanish and french populations , . seroprevalence in new york city was . -fold higher for hispanic/latinos than white people whereas death rates were . , . , . , and . -fold higher for - , - , - , and + age-classes, respectively, suggesting that either age-specific exposure or age-specific ifrs differ among these races/ethnicities. two other studies have estimated ifrs for new york city using other approaches. our age-specific estimates for ifrs in new york city were uniformly lower (by . to . -fold) than ifrs estimated from model-based inference of infections , and crudely similar to, but difficult to compare to, a crude ratio of deaths four weeks after a serosurvey divided by estimated infections from that serosurvey, because that study estimated ifr for age categories than that didn't match the published seroprevalence study or health department death data. one shortcoming of our study is that the oldest age class for the seroprevalence study was broad ( +) and combined ages ( - , - , +) in which ifrs differed -fold in other studies , whereas deaths were available in finer age classes. the two analyses we performed to quantify ifrs within this + group produced similar results because the fine resolution seroprevalence data from spain suggested only a slightly lower seroprevalence for + compared to - (~ . %; table s ). in contrast, seroprevalence in england for - and + age classes was . times lower than for - year-olds ( fig s ) ; a non-representative serosurvey of residual sera from commercial labs also showed lower seroprevalence in older age classes. if we assume the relative seroprevalence in new york city in these three age classes was similar to england, ifrs for the latter two groups would be . -fold higher: . %, and . %. this ifr for the oldest group is still substantially lower than the corresponding ifr for england (fig , s ) . the variation in seroprevalence within older age classes in some studies , emphasizes the importance of reporting both seroprevalence and deaths for sars-cov- for finer age classes to enable a more accurate understanding of the fatality of covid- for these older age groups which are most vulnerable to death from covid- . a key unanswered question concerning the fatality of covid- is how much age-specific ifrs have changed over time due to better case management and treatments. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . supplemental tables and figures table s . seroprevalence and infection fatality rate (ifr) estimates for five age classes using both confirmed and probable covid- deaths and either the raw seroprevalence values in * there was no seroprevalence estimate for the - age class so no ifr is available for the raw analysis. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint table s . detailed calculations for estimating the subgroup seroprevalence for the + age class into seroprevalence estimates for the - , - , and + age classes using the relative seroprevalence values shown in figure s . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . figure s . age-specific infection fatality ratio (ifr) of covid- (mean  % ci) on an untransformed scale with points plotted at the midpoint of the age-class on the x-axis (points are slightly jittered along the x-axis facilitate presentation). lines show age-specific ifrs for different populations, either including just confirmed covid- deaths, or estimates from "all cause" mortality. for new york city, "nyc (this study)" the figure shows the "adjusted" estimates from tables and s for both confirmed covid- deaths and confirmed + probable covid- deaths. datasets with an asterisk (*) estimate the number of infections based on seroprevalence studies; others estimate infections using either testing of passengers on the princess cruise ship (chia (russell), france (salje)) or repatriated travelers from wuhan (china(verity)). . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . the age classes used for the seroprevalence study ( - , - , - , and +) did not match the age classes of the cases and deaths provided by the new york city department of health ( - , - , - , - , and +). most importantly, the seroprevalence study grouped all individuals older than and did not include individuals younger than . previous estimates of ifr differ -fold between - ( . %; % ci: . - . ), and + ( . %; % ci: . - . ) , so we estimated ifrs for subgroups within the + group by using the finer age classes reported by the new york city department of health for cases and deaths ( - , - , and +). as a result, we performed two separate analyses using different estimates of seroprevalence for these finer age classes. for the first ("raw") analysis, we used the same single seroprevalence estimate from the + group for all three age classes that we split this group into: - , - , and +. for this raw analysis we did not estimate the ifr for the - age class. we estimated the seroprevalence in each of the age-classes for the death data using population-weighted averages from the seroprevalence study. we used estimates of census data for population estimates (https://www.baruch.cuny.edu/nycdata/population-geography/age_distribution.htm). for example, for the ifr for the - age class, we averaged the seroprevalence estimates for the - , and + age classes, weighted using the fraction of the new york city population that are in the - and - age classes. for the second ("adjusted") analysis, we used fine-resolution ( -year increments, from infancy to +) seroprevalence data from a study in spain (fig. s ) , to estimate a seroprevalence for the - group in which deaths due to sars-cov- occurred in new york city in this age group and to estimate variation in seroprevalence with the + age group for the three oldest age classes - , - , and +. we fit a simple quadratic function to the data, which captured the decrease with age in seroprevalence after age (fig s ) . we calculated population-weighted estimates of prevalence for the subgroups within the + age class, which resulted in elevated seroprevalence in - age class and lower seroprevalence in the - and + age classes relative to the + age class (table s ). we also used data for individuals - from spain to estimate seroprevalence for this age group in new york city. the ratio of seroprevalence in - year olds to seroprevalence in - year olds in spain was . . we multiplied the seroprevalence in the - age class from the study in new york city by this relative ratio to estimate seroprevalence of - year olds (table ) . an interactive web-based dashboard to track covid- in real time estimating clinical severity of covid- from the transmission dynamics in wuhan, china estimates of the severity of coronavirus disease : a model-based analysis serology-informed estimates of sars-cov- infection fatality risk in assessing the age specificity of infection fatality rates for covid- : systematic review, meta-analysis, and public policy implications. medrxiv estimating the burden of sars-cov- in france antibody prevalence for sars-cov- in england following first peak of the pandemic: react study in , adults national academies of sciences e, and medicine. framework for equitable allocation of covid- vaccine cumulative incidence and diagnosis of sars-cov- infection in new york estimating the infection fatality risk of covid- in new york city during the spring pandemic wave. medrxiv seroprevalence of antibodies to sars-cov- in sites in the united states prevalence of sars-cov- in spain (ene-covid): a nationwide, population-based seroepidemiological study funding was provided by nsf grant deb- . we thank javier perez-saez and co-authors for making their r code available (https://github.com/hopkinsidd/sarscov -ifr-gva) which facilitated the analyses presented here. key: cord- -bropr dy authors: hagen, christian a.; jamison, brent e.; giesen, kenneth m.; riley, terry z. title: guidelines for managing lesser prairie‐chicken populations and their habitats date: - - journal: wildl soc bull doi: . / - ( ) [ :gfmlpp] . .co; sha: doc_id: cord_uid: bropr dy lesser prairie‐chicken (tympanuchus pallidicinctus) populations have declined by > % since the s. these declines have concerned both biologists and private conservation groups and led to a petition to list the lesser prairie‐chicken as threatened under the endangered species act. most of the land in the current range of the lesser prairie‐chicken is privately owned, and declines have been primarily attributed to anthropogenic factors. conversion of native rangeland to cropland and excessive grazing have been implicated as leading causes in the species' decline. periodic drought probably has exacerbated these problems. little research on habitat requirements was conducted prior to . despite recent advances in the knowledge of lesser prairie‐chicken ecology, no comprehensive guidelines for management of the species have been published. in these guidelines, we provide a synopsis of our current knowledge of lesser prairie‐chicken habitat requirements and suggest management strategies to monitor, maintain, and enhance lesser prairie‐chicken populations. . because of recent declines, sport-hunting seasons were closed in new mexico ( ) and oklahoma ( ) . currently, lpchs are state-listed as threatened by colorado and considered a "warranted but precluded" threatened species by the united states fish and wildlife service (usfws) (giesen ) . concern for lpchs has led to research in all states where the species occurs to better understand population trends and habitat requirements. mixed-grass prairie communities that historically supported lpchs were thought to be comprised of regions patchily dominated by sand sagebrush (artemisia filifolia) and sand shinnery oak (quercus havardii). however, northern and eastern fringe areas of their range primarily were mixed-grass interspersed with shrubs including sand sagebrush, plum (prunus spp.), sumac (rhus spp.), and yucca (yucca spp.) (baker , copelin , horak . currently, lpchs occupy sand sagebrush and mixed-grass communities in kansas (south of the arkansas river) and colorado, sand shinnery oak and mixed-grass communities in new mexico and southwest texas panhandle, an interspersion of these shrub types in oklahoma and northeast texas panhandle, and mixed-grass prairie north of the arkansas river in kansas. this semi-arid region receives < cm of annual precipitation and sustains periodic drought that can affect short-term population trends (brown , giesen . numerous anthropogenic factors have been implicated in the decline of lpchs. conversion of native grassland communities to cropland, fire suppression leading to juniper (juniperus spp.) encroachment, excessive grazing by livestock, suburban developments, and fossil-fuel drilling and exploring are suspected to be the primary factors (giesen , woodward et al. . these factors, coupled with periodic drought, may have driven long-term population lows to critical levels. continued human encroachment and overgrazing likely will exacerbate population declines. management guidelines have been published for sage grouse (centrocercus spp.) and columbian sharp-tailed grouse (t. phasianellus columbianus), species of conservation concern (braun et al. , giesen and connelly , connelly et al. , but not for lpchs. we provide a synopsis of the current state of knowledge and provide guidelines to monitor, maintain, and enhance lpch populations and the habitats upon which they depend. lesser prairie-chickens occupy distinct vegetative communities; however, data are available primarily for populations inhabiting sand shinnery oak and sand sagebrush communities, and our guidelines reflect the available information. lesser prairie-chicken populations are surveyed annually during the spring when males congregate at lek sites. surveys of displaying males have been used to provide long-term monitoring of population trends (giesen ) . survey methods and effort vary by state. harvest statistics from check stations provided production indices (age ratios) and sex ratios in new mexico ( - , - , ) (new mexico department of game and fish, unpublished data) and texas (texas parks and wildlife department, unpublished data) . kansas and texas currently monitor harvest by using surveys mailed to random samples of hunters. these data are used to although the rate of habitat loss has slowed over the past years, lpch population trends continue to decline, suggesting that it is the quality (i.e., humaninduced or drought) of the habitat that may be limiting the recovery of these populations. estimate the number of birds harvested, but demographic data are not collected. survival estimates for lpchs are based on short-term studies of selected populations using radiotelemetry and banding data. annual survival of adult lpchs is similar to that of other prairie grouse species (hagen ) . campbell ( ) estimated annual survival of banded males in new mexico to be %, and merchant ( ) estimated survival of radiomarked females for a -month period (april-august) at %, extrapolated to months = %. in kansas, jamison ( ) estimated annual survival of radiomarked males to be %. male and female -month survival curves (april-september) that included breeding and nesting were %, and this estimate extrapolated to months= %. hagen ( ) documented age-specific annual survival of live recapture data for banded males from - in kansas, and rankings were: yearling= %, adult= %, and older adults= %. annual survival (april-april) of radiomarked females was estimated at and % for yearlings and adults, respectively (hagen ) . female survival rates were lowest in the months of may and june, but second-lowest rates occurred during winter months. twenty-nine percent of all female mortality was directly related to nesting activities (hagen ) . most lpch females attempt to nest, with - % of radiomarked birds initiating at least one nest (riley et al. , giesen , pitman . renesting attempts may vary with yearly habitat conditions and condition of females, but - % of females lose their initial clutches (giesen , pitman . nesting success (percent clutches hatching > egg) averaged % for telemetry studies (giesen ) , and hatchability (number of eggs hatched per successful nest) averaged > % (copelin , merchant , giesen , pitman . clutch size is similar rangewide (giesen ) , with an overall mean of . (se= . ) and (se= . ) eggs for first and second clutches, respectively (giesen , pitman . chick survival is highly variable but averages % rangewide (davison , schwilling , copelin , merchant , jamison , pitman . survival of chicks ( %) from fledging to first breeding (aug to apr) was similar to that of adults during the same period in kansas (pitman ) . annual variation in chick survival and nest success may have the largest impact on lpch population growth rates (hagen ) , as had been documented for greater prairie-chickens (t. cupido pinnatus) (wisdom and mills ) and attwater's prairie-chicken (t. c. attwateri) (peterson et al. ). lesser prairie-chicken populations are considered nonmigratory, and seasonal ranges and movements of individuals typically are restricted to suitable habitats within an individual's annual range (giesen ) . however, movements of lpchs in southwest kansas resembled partial migrations; approximately % of radiomarked individuals moved - km from their capture areas during nesting or postnesting and returned to the capture area during winter (hagen ) . prenesting (spring) ranges tended to be larger for females ( - ha) than spring ranges for males ( - ha) in colorado and kansas (giesen , jamison , walker . in colorado the combined annual ranges ( % ellipses) of all birds, males and females, from a lek were , - , ha ( . - . km ) (giesen ) . in kansas summer ranges ( % fixed-kernel) generally were smaller than spring ranges for both males ( ha) and females ( ha) (jamison ) . lesser prairiechickens in new mexico and oklahoma moved considerable distances in years of drought, but prenesting, nesting, and postnesting ranges of females had patterns similar to those of colorado and kansas, although they were slightly smaller (copelin , riley et al. . winter ranges of male lpchs in kansas were - ha (jamison ) and - , ha in texas (taylor and guthery a) . these enlarged ranges have been attributed to foraging in grain fields, which may be some distance from winter loafing and roosting sites in native rangeland (taylor and guthery a) . insects, seeds, leaves, buds, and cultivated grains dominate the annual diet of lpchs throughout the range (schwilling , jones a , donaldson . green leafy forage and insects were the dominant components of lpch diet from november to april and may to october, respectively (jones a) . adult lpchs relied heavily on sites of mixed-grass species of - cm in height, and seeds of -weeks fescue (vulpia octoflora), western ragweed (ambrosia psilostachya), and fragrant sumac (rhus aromatica) were important food items (jones a) . wheat, western ragweed, and blue grama (bouteloua gracilis) were common at foraging sites (donaldson ) throughout the year in oklahoma. in new mexico lpchs foraged nearly exclusively in shinnery oak-tallgrass communities during autumn and winter . fall diets were comprised of seeds ( %), vegetative material ( %), and insects ( %); winter diets were acorns ( %) and wild buckwheat (eriogonum annuum; %). vegetation at foraging sites was dominated by grass and shinnery oak, with shinnery oak more prevalent at winter sites than at autumn sites . autumn foraging sites contained more grass and fewer shrubs than did winter sites, reflecting the potential importance of shinnery oak mast and oak insect galls to lpchs in winter (davis et al. ) . small grains, short-horned grasshoppers (acrididae), beetles (coleoptera), and green wheat were the most common food items found in lpch diets of southwestern kansas (schwilling ) . similar to other regions, invertebrates and small grains comprised > % of lpch diets in summer and winter, respectively. lesser prairiechickens were documented foraging on budding willows and cottonwoods (populus spp.) in riparian areas during winter months (schwilling ) . the birds commonly forage in grain sorghum, corn, and other grain fields adjacent to native pasture from late autumn through early spring (jamison et al. a) . alfalfa was an important food source for prenesting females and lekking males in southwestern kansas (jamison ) . diets of juveniles < weeks old are thought to consist primarily of insects, specifically shorthorned grasshoppers (jones a,b; davis et al. ; jamison et al. b ). lekking. leks (breeding and display sites) generally are in open areas of short grasses surrounded by sand sagebrush or sand shinnery oak grassland (giesen ). other such sites include, but are not limited to, abandoned oil-drilling sites (oil pads) with little or no vegetation, unimproved roads with little traffic, areas treated with shrub-specific herbicide, recently burned areas, heavily grazed areas (e.g., stock tanks, mineral licks), and cultivated fields adjacent to grassland (jamison et al. a ). these sites may be located on ridgetops or knolls that are higher than surrounding topography. nesting. lesser prairie-chicken females tend to select nest sites with high visual obstruction readings (vor) (robel et al. ) and horizontal cover (giesen ) , with most females selecting sites within . km of the nearest lek. high vors can result from selecting tall residual grass cover (riley et al. ) or selecting various shrub species under which to nest (table ). in either case, average vegetation height above the nest was - cm (riley et al. ) . vegetation height at nest a lesser prairie-chicken nest in a predominantly grass pasture. a kansas pasture with a sand sagebrush density of , plants per ha. haukos and smith ( ) ; , riley et al. ( ) ; , giesen ( ) ; , pitman ( ) . sites was taller than adjacent rangeland sites (davis et al. , haukos and smith , riley et al. , giesen , pitman . in sand sagebrush habitat, successful nests often were located in areas with relatively high shrub densities (> , plants/ha) (giesen , pitman . successful nesting generally required taller and denser stands of vegetation (table ) . nest-site selection may be affected by the proximity of human disturbance, as most lpch nests were placed farther from prairie edge and anthropogenic features (e.g., power lines, pump-jacks, improved roads, and buildings) than expected at random (pitman ) . brood rearing. lesser prairie-chicken broods occupy habitats with moderate stands of cover (table ) . specifically, they forage for invertebrates in areas with abundant bare ground and approximately % canopy cover of shrubs, forbs, or grasses - cm in height (jones a , donaldson , davis et al. , ahlborn . in kansas, brood habitat was selected based on vegetation that provided high invertebrate biomass with moderate escape cover (jamison et al. a, c. a. hagen, unpublished data historically, lpch winter habitat included riparian corridors comprised of deciduous shrubs and young trees in the sand sagebrush regions (schwilling ) , and they foraged on acorns of shinnery oaks in southern parts of the range (copelin , davis et al. . cultivation and availability of small grains changed their foraging habits rangewide in the twentieth century (giesen ) . lpchs begin foraging in grain fields (where available) once harvest has begun, usually in october (schwilling , taylor and guthery a , jamison . despite this shift away from native prairie, rangeland is important for roosting and loafing habitat (baker , taylor and guthery a , jamison . in oklahoma lpchs occupied native vegetative communities comprised of grasses > cm tall and were documented using wheat, western ragweed, and blue grama (donaldson ) . in new mexico lpchs foraged almost exclusively in shinnery oak-tallgrass communities during autumn and winter ). burning. in shinnery oak grasslands, spring burning may result in increased counts of displaying males and relocation of leks to recently burned areas (cannon and knopf ) . the number of displaying males on one area increased from a preburn total of to a postburn total of . a -year study on the effects of fire on vegetation in shinnery oak rangelands of oklahoma suggested that prescribed burning could benefit lpchs by providing foraging areas, but the immediate effects of fire on nesting cover were negative, particularly when burns were conducted in spring (boyd , boyd and . a -year study on greater prairie-chickens nesting in burned and unburned landscapes in oklahoma found that % of all nests occurred in unburned sites, and those nests > m from the burn edge had the greatest probability of successfully hatching (wolfe et al. ) . synder ( ) documented impacts of fire on sand sagebrush communities. visual obstruction and canopy lesser prairie-chicken management • hagen et al. riley et al. ( ) = high plains bluestem subtype (hpbs- ), = hbps- , and = hbps- in southeastern new mexico. b pitman ( ) quantified vegetation in the sand sagebrush of southwestern kansas. c visual obstruction readings (vor) was measured (cm) by the plant growing nearest to the nest (riley et al. ) and using a vor pole (dm) by pitman ( ) . cover of sagebrush were reduced, and neither had recovered to preburn levels years post-treatment. forb recovery was highly variable in post-treatment, but perennial forbs tended to increase in the short term and annual forbs responded on a species-by-species basis. litton et al. ( ) and snyder ( ) cautioned that burning in areas of loose, sandy soils should be avoided because a lack of adequate precipitation and subsequent lack of revegetation increased the potential for wind erosion. brush-beating and herbicides. mechanical shrub removal is uncommon in habitats typically occupied by lpch; therefore, no data are available on the effects of brush-beating on the species. effects of shrub-specific herbicides on lpchs probably are compounded by interactions with livestock grazing, size of treated area, and resulting herbaceous cover (jamison et al. a ). herbicide treatment kills shrubs and allows an increase in grass cover if grass cover is not reduced by heavy grazing (donaldson , doerr and guthery , olawsky , olawsky and smith . there are no data that demonstrate how herbicides can be used to create an interspersion of different vegetation types or that any herbicide treatments will increase survival or recruitment of lpchs. negative effects of herbicide treatment on shrub cover may not become evident until > years following herbicide applications as the treated shrubs fall and decay (rodgers and sexson , jamison et al. a) . loss of native rangelands to woody cover is insidious as eastern redcedar (juniperus spp.), osage orange (maclura pomifera), and some exotics have transformed native grasslands into shrub or even forested landscapes. woodward et al. ( ) documented a negative association between landscapes with increased woody cover and lpch population indices. grazing. overgrazing is a major reason for declines in numbers of lpchs because of degradation to nesting habitat (taylor and guthery b , leslie et al. , mote et al. . however, few data demonstrate the mechanisms by which grazing impacts lpch demography. in sandy soils heavy grazing may result in a shortage of the tall residual cover (berg et al. , sims and gillen ) required for successful nesting (hoffman , jackson and dearment , litton et al. , and in firmer soils grazing may result in conversion of tall-and mid-grass communities to a shortgrass-dominated community (quinn and walgenbach ) . alternatively, moderate grazing in sandy regions can yield greater basal cover of mid-grasses and forbs (quinn and walgenbach , sims and gillen ) that may be beneficial to both nesting success and brood rearing, respectively. in oklahoma, copelin ( ) noted that lpchs used moderately grazed pastures more frequently than heavily grazed pastures. in new mexico, lpchs used lightly grazed habitats during drought years but were able to use more heavily grazed habitats in years of near-average precipitation (merchant ) . habitat restoration. prairie restoration from agricultural land to grassland has had mixed results on the lpch. conservation reserve program (crp) grasslands may provide suitable habitat, but few data are available that quantify benefits of crp to lpchs (rodgers ) . monoculture seedings have not provided additional habitat to lpchs. one study is in progress to evaluate benefits of crp fields as nesting habitat, and preliminary analyses suggest that a diversity of native tall grasses and forbs in crp seed mixes is important (t. l. fields, colorado state university, personal communication). a new conservation practice aims to restore rare and declining habitats, but these plantings are not yet well established. agriculture. conversion of native range to cropland probably is most responsible for declines in lpchs, as it has directly impacted available nesting habitat and reduced numbers of breeding birds (crawford , jamison , hagen ). most agricultural practices in cropland are suspected to affect lpch populations (crawford ) . maximum numbers of lpchs were found in areas in which - % of the landscape was planted to grain sorghum using minimum-tillage techniques (crawford ) . recently, conversion of grasslands to agriculture has slowed, as the number of hectares per year converted has not increased (jensen et al. , woodward et al. . energy development. although abandoned oil-drilling sites frequently are used as lek sites, exploration and development for gas and oil production eliminated use of leks and disrupted activity on a third lek in new mexico over a -year period (candelaria , davis et al. . in texas displaying males abandoned one lek after an elevated road was built across it (crawford and bolen b) . power lines placed near leks may negatively affect breeding activity of males (c. a. hagen, unpublished data) as raptors perching and hunting from these poles may result in reduced lekking activity. acoustical disturbance (noise pollution) from oil or gas pumps also may affect lekking displays. proposed windpower-generation farms also may increase visual fragmentation of rangeland and cause abandonment of lekking sites. pitman ( ) reported that females selected nest sites in southwestern kansas that were significantly farther from anthropogenic features (e.g., power lines, pump-jacks, improved roads, and buildings) associated with energy development than expected at random (table ). hagen ( ) found that areas used by radiomarked male and nonnesting-female lpchs were significantly farther from these same features than areas not used by lpchs (table ). these studies indicated that lpchs likely would use less-disturbed areas even though vegetation composition or structure may be similar between used and unused sites. much research is needed to determine the effects of energy exploration and development on lpchs. weather. impacts of weather on lpch populations are not well known. however, an association appears to exist between production (i.e., age ratios in harvest) and precipitation (brown , giesen . drier conditions result in sparse nesting cover and less food for chicks. harvest levels in new mexico were correlated positively with precipitation from the previous year (brown ) . population trends in colorado, as measured from lek counts, were correlated positively with the precipitation levels from years prior to census (giesen ) . translocations. generally, transplants to restore prairie grouse in unoccupied habitats have been successful (synder et al. ). however, states have conducted translocations of lpchs with little success. colorado released birds during spring over a -year reintroduction attempt, but the effort was not successful (giesen ) . texas unsuccessfully translocated lpchs during years to supplement an existing population in a native vegetative community. oklahoma translocated lpchs in an attempt to re-establish populations; one of these efforts failed and results of the other were undetermined (horton ) . it is likely that the numbers of birds released were too small and the quality of habitat at release areas was unsuitable to sustain these birds (giesen ) . hunting. the impact of modern-era sport hunting on the lpch is unknown, although market hunting in the s may have been detrimental to local populations (jackson and dearment , horak , johnson and knue . the lesser prairie-chicken once was hunted in all states within its range (giesen ). however, concerns over low populations led to closure of hunting seasons in the early s in colorado (giesen ) and in the s in new mexico and oklahoma williams , horton ) . prairie-chicken harvests (i.e., harvested birds-per-hunter ratios) have declined over the long term ( figure ). currently, a -day season and a / -bird bag/possession limit are allowed in texas and a -month season and -bird bag and -bird possession limit are allowed in kansas. lesser prairie-chicken management • hagen et al. table . distances (m) to anthropogenic features from lesser prairiechicken nest sites, use-sites and areas not likely to be frequented by lesser prairie-chickens (non-use), and areas absent of prairie chickens. ( ) and other use sites from hagen ( ) . b hagen ( ) did not differentiate between type of roads, and these distances likely reflect those of unimproved roads. disease and parasites. there is a potential for intrinsic factors to limit lpch populations (see peterson this issue); however, most studies have not documented deleterious effects at the population level. hagen et al. ( ) found low levels (< %) of mycoplamsa spp. antibodies in lpch sera (n= ) in kansas and concluded that such levels likely were not limiting to the populations. in texas, peterson et al. ( ) documented the first incidence of infectious bronchitis (a coronavirus) antibodies in lpchs. if a coronavirus should become widespread in a population, the effects could be devastating, and peterson et al. ( ) urged that further work be conducted to assess the prevalence of coronaviruses in lpchs. robel et al. ( ) reported the presence of helminthic parasites of tetrameres spp. (stomach worm), oxyspirura petrowi (eye worm), and subulura spp. (caecal worm) in , , and % of lpch carcasses (n= ), respectively. alternatively, incidence was lower in fecal samples of radiomarked individuals (n= parasitized birds, n= nonparasitized birds), but the presence of helminths did not measurably affect body mass, clutch size, nesting success, daily movements, or survival of radiomarked lpchs (robel et al. ) . genetics. van den bussche et al. ( ) found that lpchs in oklahoma and new mexico maintained high levels of genetic diversity at both nuclear and mitochondrial loci, but there was some structuring between states. hagen ( ) extended the mitochondrial work of van den bussche et al. ( ) to include populations from kansas and from colorado. there was substantial population structuring and genetic diversity across the states; notably, new mexico had the fewest haplotypes. much work is needed to identify genetically isolated populations and to determine whether there has been a loss of heterozygosity from population bottlenecks, as has been documented in greater prairie-chickens (bouzat et al. , bellinger et al. ). the following guidelines reflect our current understanding of lpch population ecology and habitat requirements. because experimental data on the effects of habitat alterations and other management activities on lpch populations are lacking or absent, these guidelines should serve as working hypotheses to be tested using the scientific method under the principles of adaptive resource management (walters and holling ) . using this approach, rigorous monitoring of management actions could provide practical information on effects of management on habitats and population responses. we recommend that each state develop and implement conservation plans for lpchs. these plans should use local groups comprised of representatives from all interested stakeholders to identify and solve regional issues within ecological regions. conservation plans should include ) quantity and quality of lpch habitat remaining in the state, ) common problems involved in conserving the lpch, and ) conditions needed to maintain healthy populations. regional variations in vegetative communities (e.g., sand sagebrush, shinnery oak, mixed shrub, or grass dominated), weather, or resource use that affect populations and their management need to be considered in conservation plans. to date, only new mexico has developed and is implementing such a plan (massey ) . because lpch populations are nonmigratory or local migrants (i.e., migrations of < km), large ecological regions should be identified as lpch management zones ( figure ). we recommend that these zones cover ecological regions (e.g., arkansas river sand hills) within a state, and that target areas no smaller than × km be identified in each zone (figure ) , as this would encompass the longest known movements of individual birds (hagen ) . identifying and prioritizing target areas will facilitate better field management and working relationships with private landowners, thus creating a framework for ensuring connectivity throughout a management zone. concentrating habitat restoration and management efforts in target areas will ensure that funding and personnel resources are used efficiently. given the fragmented nature of lpch habitat, management zones will encompass large areas of unsuitable habitat (figure ). identifying target areas where habitat restoration, management, and population monitoring are the most efficacious will facilitate protection and creation of large habitat blocks and maintain adequate levels of connectivity ( figure ). these target areas should be ranked for management action based on existing habitat quality and quantity, lpch populations, and the potential for lpch to expand into a target area. macro-scale management specific to physiognomic and ecological characteristics of lpch management zones could be conducted. a common set of recommendations that apply to the characteristics of a management zone would specify grazing regimes, furbearer harvest, and crp plantings. zone management should include lpch population monitoring; inventory of habitat quantity, quality, and connectivity; and harvest regulations for states with open seasons. there is little question that prairie-chickens are area-sensitive species, and large quantities of habitat are essential for population growth. however, habitat quality is of equal importance. the population ecology of lpch (i.e., reproductive potential and relatively stable mortality rates in specific habitats) strongly suggests that increasing breeding success is the key to increasing numbers of birds (bergerud , wisdom and mills , jamison , hagen ). thus, lpch habitat management should focus on providing adequate cover for nesting and brood rearing, given the specific cover requirements of certain habitats. cover needs are greatly increased where predation pressure is high (bergerud ) . breeding habitat. protect, maintain, and restore > , -ha tracts of native shinnery oak-tallgrass or sand sagebrush grassland within lpch management zones. these areas must be large enough and close enough to other patches (< km) to support viable lpch populations during drought. however, tracts that are smaller (> and < , ha) but with high connectivity (< km spacing) also should be included in such efforts. maintain > % native grassland (crawford ) and stabilize land-use practices in these landscapes managed for lpchs, and conserve shrub-dominated or grassland communities within > . km of lek sites because most nesting occurs within this radius (giesen , woodward et al. , pitman . nesting. provide dense shrubs and residual bunchgrasses > cm tall that provide > % vertical screening in the first cm above ground and % overhead cover for quality nesting habitat. in shinnery oak communities, sand bluestem (andropogon spp.) that is > cm in height provides suitable nesting cover. maintain or increase shrub cover in sand sagebrush communities (particularly in areas where taller species of grass have been reduced by grazing practices). manage grazing to maintain adequate height (> cm) and density of residual grasses and forbs. consider fencing areas (> . km ) to prevent grazing during the nesting season; because breeding females generally space their nests to avoid predation pressure, fencing small areas will not provide nesting cover for significant numbers of females. evaluate the feasibility of predator removal efforts to enhance nesting success of imperiled populations in small areas (< , ha) of habitat (bergerud , schroeder and baydack ) . predator removal can increase nest success of prairie grouse (lawrence and silvy ) and other ground-nesting birds (garretson et al. , witmer et al. , but long-term intensive management may not be economical. passive predator management, through relaxation of restrictions on harvest, take, or opportunistic gunning of certain furbearers, should be considered within the boundaries of management zones. nesting habitats should be interspersed with brood habitats to facilitate easier movements of young broods between habitats and reduce predation or starvation rates (bergerud , pitman . brood rearing. provide habitat with - % canopy of shrubs, forbs, or grasses that are - cm in height. in shinnery oak communities, provide vegetation dominated by warm-season grasses and shinnery oak with about % bare ground . provide vegetation composed of about - % grasses, - % shrubs (primarily shinnery oak), and - % forbs . this diversity of vegetative species and structure is important for providing the proper substrate for insects needed by juvenile lpchs . an lpch management zone (gray box) should encompass an ecological region, as in the sand sagebrush prairies of southwestern kansas (a), target areas are identified based on × -km subdivisions ( black outlines) within the management zone (b), and specific habitat patches (habitat in gray, non-habitat in white) can be monitored and managed within a target area (c). the target area in figure c includes the cimarron national grassland along the cimarron river, kansas. and , jamison et al. b . burning. prescribed burns should be conducted with great caution in lpch habitats because the vegetative response to fire is not well understood in these xeric grasslands (engle and bidwell ) . some nesting habitats may require years or more to recover before they provide adequate concealment following a fire (synder ) . experimental spring burns could be conducted at sites recently abandoned by lpchs but adjacent to areas still inhabited. conserve shinnery oak motts and protect oak bud, mast, and catkin production in relatively mesic shinnery oak communities by discing firebreaks around motts, and avoid annual burning of large areas to conserve residual nesting cover (boyd and bidwell , harrell et al. ) . alternatively, burning may be an advantageous tool to reduce juniper (wright ) or mesquite (prosopis spp.) encroachment (harrell et al. ) . given the conservative use of fire in lpch range, we recommend managing juniper using mechanical removal techniques when possible. grazing. a grazing system that maintains middle to late stages of plant succession interspersed with early stages of plant succession is optimal for lpchs (bidwell ) . to achieve this heterogeneity, grazing systems must incorporate periods of rest to prevent excessive grazing. because excessive grazing yields lower-quality concealment cover and reduces foraging habitat (particularly for nesting and brood rearing) continuous grazing is not recommended (bidwell ) . alternatively, we recommend light or moderate grazing that will ensure - % of key herbaceous species (holochek et al. ) will be available as residual nesting cover (berg et al. , snyder , sims and gillen . at least - % of a pasture should be rested completely in rotations of about once every - years engle , bidwell ) , and this vegetative response can be maintained using patch-burning methods in which - % of an area is burned annually (bidwell ) . livestock preferentially graze recently burned patches, leaving the remaining - % in various successional stages. no data are available on the effects of deferred grazing systems (which postpone grazing until grassland plants have matured) or rest-rotation grazing systems (which involve multiple pastures through which livestock are rotated) on lpch populations, but appropriate use of these systems probably would create suitable interspersion of different vegetation heights (manely et al. ) . large pastures and fewer livestock water sources also will result in a diversity of grazing pressures at the landscape level. we suggest an adaptive grazing strategy that would adjust stocking rates and season of use based on grazing system and annual precipitation. one such adap-tive framework would allocate different levels of livestock grazing based on the previous months' precipitation. this system would allow the rancher to manage the operation more effectively with few surprises. habitat restoration. conservation reserve program grasslands should range from - cm in height, as stands < cm are generally inadequate for concealment cover and those > cm seem to be avoided (r. d. rogers, kansas department of wildlife and parks [kdwp], personal communication). multispecies seedings create height and growth-form heterogeneity and must include native bunchgrasses, forbs (particularly legumes, important for structure and as a food source), and native shrubs. aggressive grasses that can crowd out other components of the mixture or grass monocultures must be avoided (r. d. rogers, kdwp, personal communication). native plant communities should be restored based on usda-nrcs ecological site guides. agriculture. prevent further cultivation of grassland surrounding leks and disturbance of lek or nest sites because such activities directly cause habitat loss. however, planting small grains or corn in existing agricultural fields adjacent to native prairie can provide additional winter food sources. minimum tillage techniques will reduce soil erosion and may benefit lpchs that are using the fields. brush treatments. much research is needed to demonstrate effects of brush treatments on lpchs. minimize the use of herbicides, except to control invasive nonnative vegetation. however, if herbicides must be used, we recommend that such treatments not reduce sand sagebrush or shinnery oak to less than % of the canopy within one year after treatment. shrub removal treatments should create a mosaic of treated and untreated areas to provide an interspersion of vegetative structures dominated by grasses and shrubs for nesting cover and areas with a diversity of vegetation for brood rearing, foraging, and adult autumn and winter cover. to create a mosaic of vegetative structures, apply tebuthiuron in strips < m wide at rates of . - . kg/ha. such treatments should be applied with a tractor-mounted sprayer (snyder ) . preserve small (< -ha) motts of tall shinnery oak that produce mast crops by excluding these areas from herbicide applications. treat shrubs in contour strips on a year rotation to provide suitable interspersion of nesting and brood-rearing habitats while reducing wind erosion of sandy soils (jamison et al. a) . avoid annual chemical brush treatment of large areas because this may reduce lpch production (wiedenfeld et al. ) . woody vegetation > m in height also should be thinned using mechanical methods when possible. similar protocols should be followed with mechanical treatment of lpch habitat to ensure that a mosaic of habitats is provided. energy development. oil and natural-gas exploration drill pads may create areas that are suitable for lek sites, but lek sites generally are not limiting to the species. the disturbance associated with exploration and production of petroleum may destroy nesting habitat or cause lek or nest abandonment and should be discouraged. if construction is unavoidable, it should occur outside of the breeding, nesting, or early brood-rearing seasons. thus we recommend that all construction and extraction be avoided from march- july. we also recommend that wind turbines or other large vertical structures be constructed > km from known or potentially occupied lpch habitat. if such structures must be placed in known lpch habitat, they should be positioned along the prairie edge or clustered in sites with other disturbances. population monitoring. it is imperative that survey methodologies and effort be standardized for estimating spring populations and recruitment across the range. improvements to lek survey methods are worthwhile (schroeder et al. , giesen but will require time and research to develop. specifically, future research is needed to determine the relationship of lek surveys to ) number of nesting females, ) variation in total population size, and ) actual densities of leks and breeding birds. in the interim, surveys that attempt to count all leks in areas known to be occupied, where occurrence is likely, and that may be restored should be implemented by wildlife and natural resource agencies rangewide (davison , hamerstrom and hamerstrom ) . this should include surveying known leks and potential sites at least times during the peak of breeding (approximately march- april) and between the minutes before and no later than hour after sunrise (crawford and bolen ) , on days with wind < km/hr and no precipitation. once methods have been standardized, spring populations of lpchs should be monitored using lek survey methods to count all active leks and search potential areas for new or satellite leks within lpch management zones. once breeding populations have been identified in these management zones, lek surveys can be used to monitor long-term population trends. lek surveys may provide an index to the size of the breeding population and may detect long-term changes in policy or land use that impact lpch populations (beck and braun ) . in the absence of mark-recapture studies and harvest information (sex and age ratios), lek surveys are the primary method of estimating minimum spring breeding populations. in states where lpchs are hunted, age ratios are difficult to estimate, given the low harvest rates and the trophy status of the species (i.e., hunters probably are not willing to contribute wings or other parts). additionally, methods for evaluating recruitment rates are important tools for monitoring management actions. we recommend that brood survey methods be developed that can be implemented and compared within each of habitats of the lpch. ideally, such methods could be compared between habitat types. hunting. current levels of harvest in texas and kansas appear to be low enough that populations should not be impacted. however, hunter surveys and lek counts should ensure that local areas are not overharvested. we recommend a permit system (similar to that implemented by texas) specific to hunting lpchs, which should facilitate more efficient recording of harvests. where possible, the use of check stations would allow evaluation of hunter success, production of juveniles, and monitoring of sex ratios. translocations. future translocations must first quantify the quality of the nesting and brood-rearing habitat at the release area; then the success of translocations should be evaluated using radiotelemetry, lek monitoring, and brood surveys. because numbers of meso-mammal predators may be elevated in fragmented landscapes and because those predators may enjoy easier access to females nesting near habitat edges, predator-control efforts implemented immediately before and after releases of birds may prove advantageous to newly supplemented or translocated populations (lawrence and silvy ) . once populations are established, predator-control efforts may no longer be cost-effective or necessary. although the rate of habitat loss has slowed over the past years, lpch population trends continue to decline, suggesting that it is the quality (i.e., humaninduced or drought) of the habitat that may be limiting the recovery of these populations. reliable knowledge is needed on restoration, the characteristics of healthy grassland and steppe ecosystems, and the relationship of grazing and lpch production. field experiments are needed that measure the effects of various levels of grazing pressure on nest success, chick survival, and invertebrate abundance. other management tools for habitat maintenance (e.g., brush treatments) and restoration (e.g., crp) also require experimental 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north dakota fish and game department a comparative study of the habitats of the lesser and greater prairie-chickens in oklahoma. dissertation identification and analysis of lesser and greater prairie chicken habitat effect of predator control on reproductive success and hen survival of attwater's prairie-chicken landscape-level evaluation of the decline of the lesser prairie-chicken in oklahoma the lesser prairie-chicken and its management in texas vegetation, cattle, and economic responses to grazing strategies and pressures long-range plan for the management of lesser prairiechickens in new mexico. new mexico department of game and fish.w- -r habitat use, reproductive success, and survival of female lesser prairie-chickens in two years of contrasting weather. thesis assessment and conservation strategy for the lesser prairie-chicken (tympanuchus pallidicinctus). kansas department of wildlife and parks effects of shinnery oak control with tebuthiuron on lesser prairie-chicken populations. thesis lesser prairie-chicken densities on tebuthiuron-treated and untreated sand shinnery oak rangelands simulation of reproductive stages limiting productivity of attwater's prairie-chicken infectious disease survey of lesser prairie-chickens in north texas lesser prairie-chicken nest site selection and nest success, juvenile gender determination and growth, and juvenile survival and dispersal in southwestern kansas influence of grazing history on the community structure of grasshoppers of a mixed grass prairie vegetative characteristics of lesser prairie-chicken brood foraging sites lesser prairie-chicken movements and home ranges in new mexico vegetative characteristics of successful and unsuccessful nests of lesser prairiechickens autumn-winter habitat use of lesser prairie-chickens (tympanuchus pallidicinctus) relationships between visual obstruction measurements and weight of grassland vegetation helminth parasites of the lesser prairie-chicken in southwestern kansas: incidence, burdens, and effects recent expansion of lesser prairie-chickens to the northern margin of their historic range impacts of extensive chemical control of sand sagebrush on breeding birds predation and the management of prairie grouse use of helicopters for estimating numbers of greater and lesser prairie-chickens in eastern colorado a study of the lesser prairie-chicken in kansas. kansas forestry, fish, and game commission rangeland steer responses to grazing in the southern plains translocation histories of prairie grouse in the united states sandsage-bluestem prairie renovation to benefit prairie grouse review of the historical and present status of the lesser prairie-chicken (tympanuchus pallidicinctus) in texas fall-winter movements, ranges, and habitat use of lesser prairie-chickens status, ecology, and management of the lesser prairie chicken. united states department of agriculture forest service general technical report rm- . rocky mountain forest and range experiment station genetic variation within and among fragmented populations fo lesser prairie-chickens (tympanuchus pallidicinctus) movements and productivity of lesser prairiechickens in southwestern kansas large-scale management experiments and learning by doing effects on shrub control and grazing on lesser prairie-chicken reproductive success year sensitivity analysis to guide population recovery: prairie chickens as an example predator management to protect endangered avian species greater prairiechicken nest success in relation to burn treatment and proximity to burn edge in oklahoma tallgrass prairie influence of landscape composition and change on lesser prairiechicken (tympanuchus pallidicinctus) populations effects of fire on southern mixed grass prairies acknowledgments. we thank d. m. davis, s. j. demaso, r. d. rogers, and t. l. fields for access to unpublished data sets. r. j. robel provided useful discussions on area requirements. two anonymous reviewers and n. j. silvy provided useful comments on an earlier draft of this manuscript. t. g. bidwell provided a review and suggestions on the rangeland management content. this project was supported in part by kansas state university's division of biology colorado division of wildlife, and texas department of parks and wildlife (w- -r). ( ) . he has been an active member of tws since , serving as student representative to the manitoba chapter ( - ) and on the planning committee for the cmps annual meeting ( ); he organized and co-chaired the symposium at the tws annual conference in bismarck from which this paper was published. his interests include habitat and population management of upland game birds, impacts of human disturbance on wildlife, demographic modeling, and habitat selection analyses. brent e. jamison currently is the upland game bird biologist for the yakama nation in south-central washington, where he directs habitat restoration work and participates in regionwide bird conservation activities including sage-grouse management. brent earned a b.s. degree in fisheries and wildlife from the university of missouri-columbia and an m.s. in wildlife biology from kansas state university. his interests include management of upland game bird populations and habitat issues affecting grassland and shrub steppe birds. kenneth m. giesen chariton, iowa ( - and a wildlife biologist for the united states forest service on the black hills national forest in spearfish, south dakota ( - and on the chequamegon national forest in park falls, wisconsin ( wisconsin ( - . he received his b.s. in fish and wildlife biology from kansas state university in , an m.s. in wildlife science from new mexico state university in , an m.s. ( ) and ph.d. ( in zoology from ohio state university. terry is a certified wildlife biologist, and his activities in the wildlife society include president of the kansas state university student chapter ( ) ( ) and the south dakota chapter ( ), secretary of the north central section ( ), board member of the central mountains and plains section ( ) ( ) ( ) ( ) , and various committee assignments. his professional interests include wildlife habitat management on agricultural, prairie wetlands, and grassland ecosystems. he also has extensive experience with legislative policy. key: cord- -zrjx ev authors: demain, arnold l; sanchez, sergio title: microbial drug discovery: years of progress date: - - journal: j antibiot (tokyo) doi: . /ja. . sha: doc_id: cord_uid: zrjx ev microbes have made a phenomenal contribution to the health and well-being of people throughout the world. in addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. this review centers on these beneficial secondary metabolites, the discovery of which goes back years to the time when penicillin was discovered by alexander fleming. back in , alexander fleming began the microbial drug era when he discovered in a petri dish seeded with staphylococcus aureus that a compound produced by a mold killed the bacteria. the mold, identified as penicillium notatum, produced an active agent that was named penicillin. later, penicillin was isolated as a yellow powder and used as a potent antibacterial compound during world war ii. by using fleming's method, other naturally occurring substances, such as chloramphenicol and streptomycin, were isolated. naturally occurring antibiotics are produced by fermentation, an old technique that can be traced back almost years, initially for beverages and food production. beer is one of the world's oldest beverages, produced from barley by fermentation, possibly dating back to the sixth millennium bc and recorded in the written history of ancient egypt and mesopotamia. another old fermentation, used to initiate the koji process, was that of rice by aspergillus oryzae. during the past years, penicillium roqueforti has been utilized for cheese production, and for the past years soy sauce in asia and bread in egypt has represented examples of traditional fermentations. natural products with industrial applications can be produced from primary or secondary metabolism of living organisms (plants, animals or microorganisms). owing to technical improvements in screening programs, and separation and isolation techniques, the number of natural compounds discovered exceeds million. among them, - % are produced by plants (alkaloids, flavonoids, terpenoids, steroids, carbohydrates, etc.) and % have a microbial origin. of all the reported natural products, approximately - % show biological activity, and of these approximately % have been obtained from microbes. furthermore, from the biologically active compounds that have been obtained so far from microbes, % are produced by actinomycetes, % by fungi and % by unicellular bacteria. the increasing role of microorganisms in the production of antibiotics and other drugs for treatment of serious diseases has been dramatic. however, the development of resistance in microbes and tumor cells has become a major problem and requires much research effort to combat it. drugs of natural origin have been classified as (i) original natural products, (ii) products derived or chemically synthesized from natural products or (iii) synthetic products based on natural product structures. evidence of the importance of natural products in the discovery of leads for the development of drugs for the treatment of human diseases is provided by the fact that close to half of the best selling pharmaceuticals in were either natural products or their derivatives. in this regard, of the top-selling drugs reported in , % were natural products or their derivatives and of these, % were antibiotics. today, the structures of around secondary metabolites have been elucidated. it is important to understand that many chemically synthesized drugs owe their origin to natural sources. applications of chemically synthesized natural metabolites include the use of a natural product derived from plant salicyclic acid derivatives present in white willow, wintergreen and meadowsweet to relieve pain and suffering. concoctions of these plants were administered by hippocrates back in the year bc, and even earlier in egypt and babylonia, for fever, pain and childbirth. synthetic salicylates were produced initially by bayer in , and later in , arthur eichengrun at bayer discovered that an acetyl derivative (aspirin), reduced acidity, bad taste and stomach irritation. these plant-based systems continue to play an essential role in health care, and it has been estimated by the world health organization (who) that approximately % of the world's inhabitants rely mainly on traditional medicines for their primary health care. other synthesized compounds originating from natural products include a nonapeptide, designated teprotide, which was isolated from the venom of the brazilian pit viper bothrops jararaca. this led to the design and synthesis of angiotensin-converting enzyme (ace) inhibitors such as captopril, which was the first marketed, orally active ace inhibitor. enalapril, another ace inhibitor used in the treatment of cardiovascular disease, was approved for marketing by the food and drug administration (fda) in . the alkaloid quinine, the active constituent of the 'fever tree' cinchona succirubra, has been known for centuries by south american indians to control malaria. during the twentieth century, massive programs to synthesize quinoline derivatives, based on the quinine prototype, were carried out. the first of the new quinolones to be used clinically as an antibacterial agent was nalidixic acid, which emerged as part of a large chemical synthesis program developed at the sterling winthrop research institute. , the program was begun when -chloro- , -dihydro- -ethyl- -oxoquinolone- -carboxylic acid was obtained as a side product during purification of chloroquine and found to have antibacterial activity. the best compound found in the program was nalidixic acid, which had remarkable activity against gram-negative bacteria and was shown to be an inhibitor of dna gyrase. its discovery led to a whole series of synthetic quinolone and fluoroquinolone antibiotics (pefloxacin, norfloxacin, ciprofloxacin, levofloxacin, ofloxacin, lomefloxacin, sparfloxacin, etc.), which have been very successful in medicine and have achieved major commercial success (table ) . it is important to appreciate that all quinolones, though synthetic, are based on the structure of the natural plant product quinine. secondary metabolites have exerted a major impact on the control of infectious diseases and other medical conditions, and the development of pharmaceutical industry. their use has contributed to an increase in the average life expectancy in the usa, which increased from years in to years (in men) and years (in women) in . probably, the most important use of secondary metabolites has been as anti-infective drugs. in , the market for such antiinfectives was us$ billion (table ) and in it was us$ billion. table shows that, among the anti-infective drugs, antivirals represent more than % of the market. two antivirals that are chemically synthesized today were originally isolated from marine organisms. they are acyclovir (active against the herpes virus by inhibition and inactivation of dna polymerase) and cytarabine (active against non-hodgkin's lymphoma). both compounds are nucleoside analog drugs, originally isolated from sponges. other antiviral applications of natural compounds are related to human immunodeficiency virus (hiv) treatment. in the pathogenesis of this disease, hiv- , similar to other retroviruses, depends on its stable integration into the host genome to facilitate efficient replication of the viral rna and maintenance of the infected state. therefore, de novo viral dna synthesized during reverse transcription is immediately integrated into the host cell dna (through the integration step), allowing for further transcription of viral rna. in the late phase of hiv viral replication, the large precursor polyprotein (gag-pol precursor, pr ) must be appropriately cleaved by a viral protease. the cleavage of the gag precursor protein of hiv is critical for the maturation and infectivity of the viral particle. without the appropriate cleavage of the precursor polyproteins, non-infectious viral particles are generally produced. to confront this problem, a tremendous effort has been made at the us national cancer institute (nci), in search of natural metabolites capable of inhibiting hiv reverse transcriptase and hiv protease. chemically synthesized derivatives of these compounds are the main agents now used against hiv. furthermore, reports have been published on natural product inhibitors of hiv integrase obtained from among the marine ascidian alkaloids; that is, the lamellarins (produced by the mollusk lamellaria sp.), and from terrestrial plants (baccharis genistelloides and achyrocline satureioides). the most consistent anti-hiv activity was observed with extracts prepared from several baccharis species. in addition, nci has been evaluating the hiv- inhibitory activity of pepstatin a, a small pentapeptide produced by several streptomyces species. it contains a unique hydroxyamino acid, statine, that sterically blocks the active site of hiv- protease. , reasons for developing new antibiotics new antibiotics that are active against resistant bacteria are required. bacteria have lived on the earth for several billion years. during this time, they encountered in nature a wide range of naturally occurring antibiotics. to survive, bacteria developed antibiotic resistance mechanisms. therefore, it is not surprising that they have become resistant to most of the natural antimicrobial agents that have been developed over the past years. this resistance increasingly limits the effectiveness of current antimicrobial drugs. the problem is not just antibiotic resistance but also multidrug resistance. in , more than % of pathogenic bacteria were estimated to be resistant to at least one of the currently available antibiotics. the so-called 'superbugs' (organisms that are resistant to most of the clinically used antibiotics) are emerging at a rapid rate. s. aureus, which is resistant to methicillin, is responsible for many cases of infections each year. the incidence of multidrug-resistant pathogenic bacteria is increasing. the infectious disease society of america (idsa) reported in that in us hospitals alone, around million people acquire bacterial infections each year (http://www.idsociety.org/content.aspx?id¼ ). s. aureus is responsible for half of the hospital-associated infections and takes the lives of approximately patients each year in the usa alone. the bacteria produce a biofilm in which they are encased and protected from the environment. biofilms can grow on wounds, scar tissues and medical implants or devices, such as joint prostheses, spinal instrumentations, catheters, vascular prosthetic grafts and heart valves. more than % of the bacterial species producing such biofilms are likely to be resistant to at least one of the drugs commonly used in anti-infectious therapy. called 'nosocomial bacteria.' more than % of sepsis cases in hospitals are caused by gram-negative bacteria. among them, pseudomonas aeruginosa accounts for almost % of these opportunistic infections. they represent a serious problem in patients hospitalized with cancer, cystic fibrosis and burns, causing death in % of cases. other infections caused by pseudomonas species include endocarditis, pneumonia and infections of the urinary tract, central nervous system, wounds, eyes, ears, skin and musculoskeletal system. this bacterium is another example of a natural multidrug-resistant microorganism. although many strains are susceptible to gentamicin, tobramycin and amikacin, resistant forms have also developed. these multidrug-resistant bacteria make hospitals ''dangerous places to be, especially if you are sick, but even if not.'' although we are seeing a steady increase in resistance in almost every pathogen to most of the current antibiotics over time, not all the antibacterial agents show the same rate of resistance development. for example, antimicrobials such as rifampicin, which targets single enzymes, are most susceptible to the development of resistance, whereas agents that inactivate several targets irreversibly generate resistance more slowly. in addition to the antibiotic-resistance problem, new families of anti-infective compounds are needed to enter the marketplace at regular intervals to tackle the new diseases caused by evolving pathogens. at least new diseases emerged in the s and s and they are growing in incidence. emerging infectious organisms often encounter hosts with no prior exposure to them and thus represent a novel challenge to the host's immune system. several viruses responsible for human epidemics have made a transition from animal host to humans and are now transmitted from human to human. hiv, responsible for the acquired immunodeficiency syndrome (aids) epidemic, is one example. although it has not been proven, it is suspected that severe acute respiratory syndrome (sars), caused by the sars coronavirus, also evolved from a different species. in the early s, after decades of decline, the incidence of tuberculosis began to increase. the epidemic took place owing to inadequate treatment regimens, a diminished public health system and the onset of the hiv/aids epidemic. the who has predicted that between and , nearly billion people will become infected with mycobacterium tuberculosis and that this disease will cost the lives of million people. sexually transmitted diseases have also increased during these decades, especially in young people (aged - years). the human papillomavirus, chlamydia, genital herpes, gonorrhea and hiv/aids are examples. hiv/aids has infected more than million people in the world. together with other diseases such as tuberculosis and malaria, hiv/aids accounts for over million illnesses and more than million deaths each year. additional evolving pathogens include the (i) ebola virus, which causes the viral hemorrhagic fever syndrome with a resultant mortality rate of %; (ii) the bacterium legionella pneumophila, a ubiquitous aquatic organism that lives in warm environments, which causes legionnaire's disease, a pulmonary infection; (iii) the hantavirus, which can infect humans with two serious illnesses: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome; (iv) at least three species of bacteria from the genus borrelia, which cause lyme disease, an emerging infection. in this case, the infection is acquired from the bite of ticks belonging to several species of the genus ixodes. borrelia burgdorferi is the predominant cause of lyme disease in the us, whereas borrelia afzelii and borrelia garinii are implicated in most european cases. the disease presentation varies widely, and may include a rash and flu-like symptoms in its initial stage, followed by musculoskeletal, arthritic, neurologic, psychiatric and cardiac manifestations. in the majority of cases, symptoms can be eliminated with antibiotics, especially if the treatment begins early in the course of illness. however, late or inadequate treatment can lead to 'late-stage' lyme disease that can be disabling and difficult to treat. (v) other evolving pathogens include the escherichia coli :h (enterohemorrhagic e. coli), a strain that causes colitis and bloody diarrhea by producing a toxin called shiga toxin, which damages the intestines. it is estimated that this bacterium causes infection in more than patients a year in the usa. another example is (vi) cryptosporidium, an obligate intracellular parasite commonly found in lakes and rivers. cryptosporidium parvum is one of the common species affecting the digestive and respiratory organs. intestinal cryptosporidiosis is characterized by severe watery diarrhea. pulmonary and tracheal cryptosporidiosis in humans is associated with coughing and is frequently a low-grade fever. people with severely weakened immune systems are likely to have more severe and more persistent symptoms than healthy individuals. in the developing world, nearly % of the infectious disease deaths are caused by six diseases or disease processes: acute respiratory infections, diarrhea, tuberculosis, hiv, measles and malaria. in both the developing and developed nations, the leading cause of death by a wide margin is acute respiratory disease. in the developing world, acute respiratory infections are attributed primarily to seven bacteria: bordetella pertussis, streptococcus pneumoniae, haemophilus influenzae, staphylococcus aureus, mycoplasma pneumoniae, chlamydophila pneumoniae and chlamydia trachomatis. in addition, the major viral causes of respiratory infections include respiratory syncytial virus, human parainfluenza viruses and , influenza viruses a and b, as well as some adenoviruses. these diseases are highly destructive in economic and social as well as in human terms and cause approximately million deaths per year, and innumerable serious illnesses besides affecting the economic growth, development and prosperity of human societies. morse identified six general factors in the emergence of infectious diseases: ecological changes, human demographics and behavior, international travel, technology and industry, microbial adaptation and change, and breakdown in public health measures. one additional reason for developing new antibiotics is related to their own toxicity. as with other therapeutic agents, the use of antibiotics may also cause side effects in patients. these include mild reactions such as upset stomach, vomiting and diarrhea (cephalosporins, macrolides, penicillins and tetracyclines), rash and other mild and severe allergic reactions (cephalosporins and penicillins), sensitivity to sunlight (tetracyclines), nervousness, tremors and seizures (quinolones). some side effects are more severe and, depending on the antibiotic, may disrupt the hearing function (aminoglycosides), kidneys (aminoglycosides and polypeptides) or liver (rifampin). during recent decades, we have seen an increasing number of reports on the progressive development of bacterial resistance to almost all available antimicrobial agents. in the s, the major problem was the multidrug resistance of gram-negative bacteria, but later in the s the gram-positive bacteria became important, including methicillin-resistant staphylococci, penicillin-resistant pneumococci and vancomycin-resistant enterococci. in the past, the solution to the problem has depended primarily on the development of novel antimicrobial agents. however, the number of new classes of antimicrobial agents being developed has decreased dramatically in recent years. the advent of resistant gram-positive bacteria has been noticed by the pharmaceutical, biotechnology and academic communities. some of these groups are making concerted efforts to find novel antimicrobial agents to meet this need. a new glycopeptide antibiotic, teicoplanin, was developed against infections with resistant gram-positive bacteria, especially bacteria resistant to the glycopeptide vancomycin. in another instance, the approach involved the redesign of a mixture of two compounds, called streptogramin, into a new mixture, called pristinamycin, to allow administration of the drug parenterally and in higher doses than the earlier oral preparation. the two components of streptogramin, quinupristin and dalfopristin, were chemically modified to allow intravenous administration. the new combination, pristinamycin, was approved by the fda for use against infections caused by vancomycin-resistant enterococcus faecium. additional moves against resistant microorganisms are the glycylcyclines developed to treat tetracycline-resistant bacteria. these modified tetracyclines show potent activity against a broad spectrum of gram-positive and gram-negative bacteria, including strains that carry the two major tetracycline-resistance determinants, involving efflux and ribosomal protection. two of the glycylcyline derivatives, dmg-mino and dmg-dmdot, have been tested against a large number of clinical pathogens isolated from various sources. the spectrum of activity of these compounds includes organisms with resistance to antibiotics other than tetracyclines; for example, methicillin-resistant staphylococci, penicillin-resistant s. pneumoniae and vancomycin-resistant enterococci. tigecycline was approved by the fda in as an injectable antibiotic. among the novel class of antimicrobial agents used in treating resistance to gram-positive infections, we can also mention the cyclic lipopeptide antibiotic daptomycin produced by streptomyces roseosporus. this compound was approved in by the fda for skin infections resulting from complications following surgery, diabetic foot ulcers and burns. it represents the first new natural antibiotic approved in many years. its mode of action is distinct from any other approved antibiotic: it rapidly kills gram-positive bacteria by disrupting multiple aspects of bacterial membrane function (by binding irreversibly to the bacterial cell membrane, causing membrane depolarization, destroying the ion concentration gradient and provoking the efflux of k + ). it acts against most clinically relevant gram-positive bacteria (staphylococcus aureus, streptococcus pyogenes, streptococcus agalactiae, streptococcus dysgalactiae subsp. equisimilis and enterococcus faecalis), and retains in vitro potency against isolates resistant to methicillin, vancomycin and linezolid. traditionally, these infections were treated with penicillin and cephalosporins, but resistance to these agents became widespread. [ ] [ ] [ ] [ ] daptomycin seems to have a favorable side effect profile, and it might be used to treat patients who cannot tolerate other antibiotics. telithromycin, a macrolide antibiotic, is the first orally active compound of a new family of antibacterials named the ketolides. it shows potent activity against pathogens implicated in communityacquired respiratory tract infections, irrespective of their b-lactam, macrolide or fluoroquinolone susceptibility. some of the microorganisms susceptible to this antibiotic are pneumococci, h. influenzae and moraxella catarrhalis, including b-lactamase-positive strains. in addition, telithromycin has a very low potential for selection of resistant isolates or induction of cross-resistance found with other macrolides. clavulanic acid, first detected in streptomyces clavuligerus, contains a bicyclic b-lactam ring fused to an oxazolidine ring with an oxygen in place of a sulfur, a b-hydroxyethylidene substituent at c- and no acylamino group at c- . it was first described in and shown to be a potent inhibitor of the b-lactamases produced by staphylococci and plasmid-mediated b-lactamases of e. coli, klebsiella, proteus, shigella, pseudomonas and haemophilus. although it is a broad-spectrum antibiotic, clavulanic acid possesses only very low antibacterial activity. therefore, the molecule has been combined, as a b-lactamase inhibitor, with a variety of broad-spectrum semisynthetic penicillins. for example, when administered with amoxicillin, it is used for the treatment of infections caused by b-lactamase-producing pathogenic bacteria. it has world sales of over us$ billion, and in it was the second largest selling antibacterial drug. clavulanic acid can also be combined with ticarcillin, which is a penicillin effective against organisms such as e. coli, proteus, salmonella, haemophilus, pseudomonas and s. aureus. it is normally used in hospitals for treating severe infections affecting blood or internal organs, bones and joints, upper or lower airways or skin and soft tissue. the combination extends ticarcillin antimicrobial activity by inhibiting the action of the b-lactamases produced by certain bacteria. mycosis is a condition in which fungi pass the resistance barriers of the human or animal body and establish infections. these organisms are harmless most of the time, but sometimes they can cause fungal infections. in most cases, these infections are not life threatening. however, when they are deeply invasive and disseminated, they lead to more serious infections, particularly in critically ill patients, elderly people and those who have conditions that affect the immune system (by disease or through the use of immunosuppressive agents). in addition, the use of antineoplastic and broad-spectrum antibiotics, prosthetic devices and grafts, and more aggressive surgery has increased invasive fungal infections. patients with burns, neutropenia, pancreatitis or after organ transplantation ( % of liver transplants, - % of heart transplants and % of kidney transplants) are also predisposed to fungal infection. approximately % of death from nosocomial infections are caused by fungi, and % of these are caused by candida and aspergillus, although cryptococcus spp., fusarium spp., scedosporium spp., penicillium spp. and zygomycetes are increasingly involved. pulmonary aspergillosis is the main factor involved in the death of recipients of bone marrow transplants, and pneumocystis carinii is the leading cause of death in aids patients from europe and north america. the rising incidence of invasive fungal infections and the emergence of broader fungal resistance have led to the need for novel antifungal agents. amphotericin b is the first-line therapy for systemic infection because of its broad spectrum and fungicidal activity. however, considerable side effects limit its clinical utility. echinocandins are large lipopeptide molecules that inhibit the synthesis of , -b-dglucan, a key component of the fungal cell wall. three echinocandins (caspofungin, micafungin and anidulafungin) have reached the market. caspofungin is also known as pneumocandin or mk- . this compound was the first cell-wall-active antifungal approved as a new injectable antifungal; this was in . it irreversibly inhibits , -b-d-glucan synthase, preventing the formation of glucan polymers and disrupting the integrity of fungal cell walls. it is more active and less toxic than amphotericin b and shows a broad spectrum of activity against candida (including fluconozole resistance), aspergillus, histoplasma and p. carinii, the major cause of hiv death. micafungin is licensed for clinical use in asian countries and in the us. this compound exhibits extremely potent antifungal activity against clinically important fungi, including aspergillus and azole-resistant strains of candida. in animal studies, micafungin is as efficacious as amphotericin b with respect to improvement of survival rate. it is characterized by a linear pharmacokinetic profile and substantially fewer toxic effects. anidulafungin is currently licensed in the us. although several new antifungal drugs have been developed in the past years, some patients remain resistant to treatments. the main reasons for this include intrinsic or acquired antifungal resistance, organ dysfunction preventing the use of some agents and drug interactions. in addition, some drugs penetrate poorly into sanctuary sites, including the eye and urine, and others are associated with considerable adverse events. however, there has been some progress. posaconazole is a new member of the triazole class of antifungals. it has shown clinical efficacy in the treatment of oropharyngeal candidiasis and has potential as a salvage therapy for invasive aspergillosis, zygomycosis, cryptococcal meningitis and a variety of other fungal infections. it is available as an oral suspension and has a favorable toxicity profile. the wide spectrum of posaconazole activity in in vitro studies, animal models and preliminary clinical studies suggests that it represents an important addition to the antifungal armamentarium. in addition to the screening programs for antibacterial activity, the pharmaceutical industry has extended these programs to other disease areas. , microorganisms are a prolific source of structurally diverse bioactive metabolites and have yielded some of the most important products of the pharmaceutical industry. microbial secondary metabolites are now being used for applications other than antibacterial, antifungal and antiviral infections. for example, immunosuppressants have revolutionized medicine by facilitating organ transplantation. other applications include antitumor drugs, enzyme inhibitors, gastrointestinal motor stimulator agents, hypocholesterolemic drugs, ruminant growth stimulants, insecticides, herbicides, coccidiostats, antiparasitics vs coccidia, helminths and other pharmacological activities. further applications are possible in various areas of pharmacology and agriculture, developments catalyzed by the use of simple enzyme assays for screening before testing in intact animals or in the field. in the year , approximately million new cases of cancer were diagnosed in the world, resulting in million cancer-related deaths. the tumor types with the highest incidence were lung ( . %), breast ( . %) and colorectal ( . %). microbial metabolites are among the most important of the cancer chemotherapeutic agents. they started to appear around with the discovery of actinomycin and since then many compounds with anticancer properties have been isolated from natural sources. more than % of the current compounds with antineoplasic activity were originally isolated as natural products or are their derivatives. among the approved products deserving special attention are actinomycin d, anthracyclines (daunorubicin, doxorubicin, epirubicin, pirirubicin and valrubicin), bleomycin, mitosanes (mitomycin c), anthracenones (mithramycin, streptozotocin and pentostatin), enediynes (calcheamycin), taxol and epothilones. actinomycin d is the oldest microbial metabolite used in cancer therapy. its relative, actinomycin a, was the first antibiotic isolated from actinomycetes. the latter was obtained from actinomyces antibioticus (now streptomyces antibioticus) by waksman and woodruff. as it binds dna at the transcription initiation complex, it prevents elongation by rna polymerase. this property, however, confers some human toxicity and it has been used primarily as an investigative tool in the development of molecular biology. despite the toxicity, however, it has served well against wilms tumor in children. the anthracyclines are some of the most effective antitumor compounds developed, and are effective against more types of cancer than any other class of chemotherapy agents. they are used to treat a wide range of cancers, including leukemias, lymphomas, and breast, uterine, ovarian and lung cancers. anthracyclines act by intercalating dna strands, which result in a complex formation that inhibits the synthesis of dna and rna. it also triggers dna cleavage by topoisomerase ii, resulting in mechanisms that lead to cell death. in their cytotoxic effects, the binding to cell membranes and plasma proteins plays an important role. their main adverse effects are heart damage (cardiotoxicity), which considerably limits their usefulness, and vomiting. the first anthracycline discovered was daunorubicin (daunomycin) in , which is produced naturally by streptomyces peucetius. doxorubicin (adriamycin) was developed in . another anthracycline is epirubicin. this compound, approved by the fda in , is favored over doxorubicin in some chemotherapy regimens as it appears to cause fewer side effects. epirubicin has a different spatial orientation of the hydroxyl group at the ¢ carbon of the sugar, which may account for its faster elimination and reduced toxicity. epirubicin is primarily used against breast and ovarian cancer, gastric cancer, lung cancer and lymphomas. valrubicin is a semisynthetic analog of doxorubicin approved as a chemotherapeutic drug in and used to treat bladder cancer. bleomycin is a non-ribosomal glycopeptide microbial metabolite produced as a family of structurally related compounds by the bacterium streptomyces verticillus. first reported by umezawa et al. in , bleomycin obtained fda approval in . when used as an anticancer agent (inducing dna strand breaks), the chemotherapeutic forms are primarily bleomycins a and b . mitosanes are composed of several mitomycins that are formed during the cultivation of streptomyces caespitosus. although the mitosanes are excellent antitumor agents, they have limited utility owing to their toxicity. mitomycin c was approved by the fda in , showing activity against several types of cancer (lung, breast, bladder, anal, colorectal, head and neck), including melanomas and gastric or pancreatic neoplasms. recently, mitomycin dimers have been explored as potential alternatives for lowering toxicity and increasing efficiency. mithramycin (plicamycin) is an antitumor aromatic polyketide produced by streptomyces argillaceous that shows antibacterial and antitumor activity. it is one of the older chemotherapy drugs used in the treatment of testicular cancer, disseminated neoplasms and hypercalcemia. it binds to g-c-rich dna sequences, inhibiting the binding of transcription factors such as sp , which is believed to affect neuronal survival/death pathways. it may also indirectly regulate gene transcription by altering histone methylation. with repeated use, organotoxicity (kidney, liver and hematopoietic system) can become a problem. streptozotocin is a microbial metabolite with antitumor properties, produced by streptomyces achromogenes. chemically, it is a glucosamine-nitroso-urea compound. as with other alkylating agents in the nitroso-urea class, it is toxic to cells by causing damage to dna, although other mechanisms may also contribute. the compound is selectively toxic to the b-cells of the pancreatic islets. it is similar enough to glucose to be transported into the cell by the glucose transport protein of these cells, but it is not recognized by the other glucose transporters. as b-cells have relatively high levels of glucose permease, the relative streptozotocin toxicity for these b-cells can be explained. in , fda granted approval for streptozotocin as a treatment for pancreatic islet cell cancer. pentostatin (deoxycoformycin) is an anticancer chemotherapeutic drug produced by s. antibioticus. it is classified as a purine analog, which mimics the nucleoside adenosine and thus tightly binds and inhibits adenosine deaminase (k i of . Â À m). it interferes with the cell's ability to process dna. pentostatin is commonly used to treat hairy cell leukemia, acute lymphocytic leukemia, prolymphocytic leukemia (b-and t-cell origin), t-cell leukemia and lymphoma. however, it can cause kidney, liver, lung and neurological toxicity. the fda granted approval for pentostatin in . calicheamicins are highly potent antitumor microbial metabolites of the enediyne family produced by micromonospora echinospora. their antitumor activity is apparently due to the cleavage of double-stranded dna. they are highly toxic, but it was possible to introduce one such compound into the clinic by attaching it to an antibody that delivered it to certain cancer types selectively. this ingenious idea of the wyeth laboratories avoided the side effects of calicheamicin. in this regard, gemtuzumab is effective against acute myelogenous leukemia (aml). calicheamicin is bound to a monoclonal antibody against a transmembrane receptor (cd ) expressed on cells of monocytic/myeloid lineage. cd is expressed in most leukemic blast cells, but in normal hematopoietic cells the intensity diminishes with maturation. it was approved by the fda for use in patients over the age of years with relapsed aml who are not considered candidates for standard chemotherapy. a successful non-actinomycete molecule is taxol (paclitaxel), which was first isolated from the pacific yew tree, taxus brevifolia, but is also produced by the endophytic fungi taxomyces andreanae and nodulisporium sylviforme. this compound inhibits rapidly dividing mammalian cancer cells by promoting tubulin polymerization and interfering with normal microtubule breakdown during cell division. the drug also inhibits several fungi (pythium, phytophthora and aphanomyces) by the same mechanism. in , taxol was approved for refractory ovarian cancer, and today it is used against breast and advanced forms of kaposi's sarcoma. a new formulation is available in which paclitaxel is bound to albumin. taxol sales amounted to us$ . billion in for bristol myers-squibb, representing % of the company's pharmaceutical sales and its third largest selling product. currently, taxol production uses plant cell fermentation technology. the epothilones (a name derived from its molecular features: epoxide, thiazole and ketone) are macrolides originally isolated from the broth of the soil myxobacterium sorangium cellulosum as weak agents against rust fungi. they were identified as microtubulestabilizing drugs, acting in a similar manner to taxol. , however, they are generally - times more potent than taxol in inhibiting cell growth in cultures. five analogs are now undergoing investigation as candidate anticancer drugs, and their preclinical studies have indicated a broad spectrum of antitumor activity, including taxol-resistant tumor cells. with the best currently available therapies, the median survival time for patients with metastatic breast cancer is only - years, and many patients develop resistance to taxanes or other chemotherapy drugs. one epothilone, ixabepilone, was approved in october by the fda for use in the treatment of aggressive metastatic or locally advanced breast cancer no longer responding to currently available chemotherapies. in tumor cells, p-glycoprotein reduces intracellular antitumor drug concentrations, thereby limiting access of chemotherapeutic substrates to the site of action. the epothilones are attractive because they are active against p-glycoprotein-producing tumors and have good solubility. epothilone b is a -membered polyketide macrolactone with a methylthiazole group connected to the macrocycle by an olefinic bond. testicular cancer is the most common cancer diagnosis in men between the ages of and years, with approximately cases detected in the united states annually. the majority ( %) of testicular neoplasms are germ cell tumors, which are relatively uncommon carcinomas, accounting for only % of all male malignancies. remarkable progress has been made in the medical treatment of advanced testicular cancer, with a substantial increase in cure rates from approximately % in the early s to almost % today. , this cure rate is the highest of any solid tumor, and improved survival is primarily due to effective chemotherapy. a major advance in chemotherapy for testicular germ cell tumors was the introduction of cisplatin in the mid- s. two chemotherapy regimens are effective for patients with a good testicular germ cell tumor prognosis: four cycles of etoposide and cisplatin or three cycles of bleomycin, etoposide and cisplatin. of the latter three agents, bleomycin and etoposide are natural products. enzyme inhibitors have received increasing attention as useful tools, not only for the study of enzyme structures and reaction mechanisms but also for potential utilization in medicine and agriculture. several enzyme inhibitors with various industrial uses have been isolated from microbes. the most important are ( ) clavulanic acid, the inhibitor of b-lactamases discussed above in the section 'moves against antibiotic resistance development in bacteria,' and the statins, hypocholesterolemic drugs presented below in the section 'hypocholesterolemic drugs.' some of the common targets for other inhibitors are glucosidases, amylases, lipases, proteases and xanthine oxidase (xo). acarbose is a pseudotetrasaccharide made by actinoplanes sp. se . it contains an aminocyclitol moiety, valienamine, which inhibits intestinal a-glucosidase and sucrase. this results in a decrease in starch breakdown in the intestine, which is useful in combating diabetes in humans. amylase inhibitors are useful for the control of carbohydratedependent diseases, such as diabetes, obesity and hyperlipemia. , amylase inhibitors are also known as starch blockers because they contain substances that prevent dietary starches from being absorbed by the body. the inhibitors may also be useful for weight loss, as some versions of amylase inhibitors do show potential for reducing carbohydrate absorption in humans. , the use of amylase inhibitors for the treatment of rumen acidosis has also been reported. examples of microbial a-amylase inhibitors are paim, obtained from culture filtrates of streptomyces corchorushii, and tai-a, tai-b, oligosaccharide compounds from streptomyces calvus tm- . lipstatin is a pancreatic lipase inhibitor produced by streptomyces toxytricini that is used to combat obesity and diabetes. it interferes with the gastrointestinal absorption of fat. the commercial product is tetrahydrolipstatin, which is also known as orlistat. in the pathogenic processes of some diseases, such as emphysema, arthritis, pancreatitis, cancer and aids, protease inhibitors are potentially powerful tools for inactivating target proteases. examples of microbial products include antipain, produced by streptomyces yokosukaensis, leupeptin from streptomyces roseochromogenes and chymostatin from streptomyces hygroscopicus. leupeptin is produced by more than species of actinomycetes. xo catalyzes the oxidation of hypoxanthine to uric acid through xanthine. an excessive accumulation of uric acid in the blood, called hyperuricemia, causes gout. the inhibitors of xo decrease the uric acid levels, which result in an antihyperuricemic effect. a potent inhibitor of xo, hydroxyakalone, was purified from the fermentation broth of agrobacterium aurantiacum sp. nov., a marine bacterial strain. fungal products are also used as enzyme inhibitors against cancer, diabetes, poisonings, alzheimer's disease, etc. the enzymes inhibited include acetylcholinesterase, protein kinase, tyrosine kinase, glycosidases and others. immunosuppresants suppressor cells are critical in the regulation of the normal immune response. an individual's immune system is capable of distinguishing between native and foreign antigens and of mounting a response only against the latter. a major role has been established for suppressor t lymphocytes in this phenomenon. suppressor cells also play a role in regulating the magnitude and duration of the specific antibody response to an antigenic challenge. suppression of the immune response either by drugs or by radiation, to prevent the rejection of grafts or transplants or to control autoimmune diseases, is called immunosuppression. a number of microbial compounds capable of suppressing the immune response have been discovered. cyclosporin a was originally introduced as a narrow-spectrum antifungal peptide produced by the mold, tolypocladium nivenum (originally classified as trichoderma polysporum and later as tolypocladium inflatum), by aerobic fermentation. cyclosporins are a family of neutral, highly lipophilic, cyclic undecapeptides containing some unusual amino acids, synthesized by a non-ribosomal peptide synthetase, cyclosporin synthetase. discovery of the immunosuppressive activity led to its use in heart, liver and kidney transplants and to the overwhelming success of the organ transplant field. cyclosporin was approved for use in . it is thought to bind to the cytosolic protein cyclophilin (immunophilin) of immunocompetent lymphocytes, especially t lymphocytes. this complex of cyclosporin and cyclophilin inhibits calcineurin, which under normal circumstances is responsible for activating the transcription of interleukin- . it also inhibits lymphokine production and interleukin release and therefore leads to a reduced function of effector t cells. sales of cyclosporin a have reached us$ . billion per year. other important transplant agents include sirolimus (rapamycin) and tacrolimus (fk ), which are produced by actinomycetes. rapamycin is especially useful in kidney transplants as it lacks the nephrotoxicity seen with cyclosporin a and tacrolimus. it is a macrolide, first discovered in as a product of s. hygroscopicus, and was initially proposed as an antifungal agent. however, this was abandoned when it was discovered that it had potent immunosuppressive and antiproliferative properties. this compound binds to the immunophilin fk -binding protein (fkbp ), and this binary complex interacts with the rapamycin-binding domain and inactivates a serine-threonine kinase termed the mammalian target of rapamycin. the latter is known to control proteins that regulate mrna translation initiation and g progression. the antiproliferative effect of rapamycin has also been used in conjunction with coronary stents to prevent restenosis, which usually occurs after the treatment of coronary artery disease by balloon angioplasty. rapamycin also shows promise in treating tuberous sclerosis complex (tsc), a congenital disorder that leaves sufferers prone to benign tumor growth in the brain, heart, kidneys, skin and other organs. in a study of rapamycin as a treatment for tsc, university of california, los angeles (ucla) researchers observed a major improvement in mice regarding retardation related to autism. as rapamycin has poor aqueous solubility, some of its analogs, rad (everolimus), cci- (tensirolimus) and ap (ariad), have been developed with improved pharmaceutical properties. everolimus is currently used as an immunosuppressant to prevent the rejection of organ transplants. although it does not have fda approval in the usa, it is approved for use in europe and australia, and phase iii trials are being conducted in the us. everolimus may have a role in heart transplantation as it has been shown to reduce chronic allograft vasculopathy in such transplants. everolimus is also used in drug-eluting coronary stents as an immunosuppressant to prevent rejection. cci- is a rapamycin ester that can be converted to rapamycin in vivo. rad is a rapamycin analog currently being investigated in phase ii trials for recurrent endometrial cancer as a single agent, and in phase i/ii trials for the treatment of glioblastoma in combination with the inhibitor of certain epidermal growth factor receptor and vascular endothelial growth factor receptor family members. ap is a novel non-prodrug rapamycin analog with a nonlinear pharmacokinetic behavior that has demonstrated antiproliferative activity against several human tumor cell lines in vitro and against experimental tumors in vivo. this agent is currently under evaluation in phase i-ii trials, including patients with different tumors. two additional small-molecule rapamycin analogs, ap and ap , are currently in preclinical development for the treatment of bone metastases and primary bone cancer. tacrolimus (fk ) was discovered in in japan. it is produced by streptomyces tsukubaensis. however, its use was almost abandoned because of dose-associated toxicity. dr thomas starzl (university of pittsburgh) rescued it by using lower doses, realizing that it was approximately times more active as an immunosuppressive than cyclosporin a. it was introduced in japan in , and in it was approved by the fda for use as an immunosuppressant in liver transplantation. furthermore, its use has been extended to include bone marrow, cornea, heart, intestines, kidney, lung, pancreas, trachea, small bowel, skin and limb transplants, and for the prevention of graft-vs-host disease. topically, it is also used against atopic dermatitis, a widespread skin disease. in the laboratory, tacrolimus inhibits the mixed lymphocyte reaction, the formation of interleukin- by t lymphocytes, and the formation of other soluble mediators, including interleukin- and interferon g. recently, it has been reported that tacrolimus inhibits tumor growth factor-b-induced signaling and collagen synthesis in human lung fibroblastic cells. this factor plays a pivotal role in tissue fibrosis, including pulmonary fibrosis. therefore, tacrolimus may be useful for the treatment of pulmonary fibrosis, although its use in the acute inflammatory phase may exacerbate lung injury. hypocholesterolemic drugs atherosclerosis is generally viewed as a chronic, progressive disease characterized by the continuous accumulation of atheromatous plaque within the arterial wall. the past two decades have witnessed the introduction of a variety of anti-atherosclerotic therapies. the statins form a class of hypolipidemic drugs used to lower cholesterol by inhibiting the enzyme hmg-coa reductase, the rate-limiting enzyme of the mevalonate pathway of cholesterol biosynthesis. inhibition of this enzyme in the liver stimulates low-density lipoprotein (ldl) receptors, resulting in an increased clearance of ldl from the bloodstream and a decrease in blood cholesterol levels. through their cholesterol-lowering effect, they reduce the risk of cardiovascular disease, prevent stroke and reduce the development of peripheral vascular disease. in addition, they are anti-thrombotic and antiinflammatory. currently there are a number of statins in clinical use. the entire group of statins reached an annual market of nearly us$ billion before it became a generic pharmaceutical. the first member of the group (compactin; mevastatin) was isolated as an antibiotic product of penicillium brevicompactum and later from penicillium citrinum. although not of commercial importance, compactin's derivatives achieved overwhelming medical and commercial success. an ethylated form, known as lovastatin (monacolin k; mevinolin), was isolated in the s in the broths of monascus ruber and aspergillus terreus. lovastatin, the first commercially marketed statin, was approved by the fda in . a semisynthetic derivative of lovastatin is simvastatin, a major hypocholesterolemic drug, selling for us$ billion per year before becoming generic. another statin, pravastatin (us$ . billion per year), is made through different biotransformation processes from compactin by streptomyces carbophilus and actinomadura sp. other genera involved in the production of statins are doratomyces, eupenicillium, gymnoascus, hypomyces, paecilomyces, phoma, trichoderma and pleurotus. a synthetic compound, modeled from the structure of the natural statins, is atorvastin, which has been the leading drug of the entire pharmaceutical industry in terms of market share (approximately us$ billion per year) for many years. an insecticide is a pesticide used against insects in all developmental forms. they include ovicides and larvicides used against the eggs and larvae of insects, respectively. insecticides are used in agriculture, medicine, industry and households. the use of insecticides is believed to be one of the major factors behind the increase in agricultural productivity in the twentieth century. synthetic insecticides pose some hazards, whereas natural insecticides offer adequate levels of pest control and pose fewer hazards. microbially produced insecticides are especially valuable because their toxicity to non-target animals and humans is extremely low. compared with other commonly used insecticides, they are safe for both the pesticide users and consumers of treated crops. the action of microbial insecticides is often specific to a single group or species of insects, and this specificity means that most microbial insecticides do not naturally affect beneficial insects (including predators or parasites of pests) in treated areas. the spinosyns (a group) are a group of natural products produced by saccharopolyspora spinosa that were discovered in . the researchers isolated spinosyn a and d, as well as minor analogs. they are active on a wide variety of insect pests, especially lepidopterans and dipterans, but do not have antibiotic activity. the compounds attack the nervous system of insects by targeting two key neurotransmitter receptors, with no cross-resistance to other known insecticides. the spinosyns are a family of macrolides with carbon atoms, containing four connected rings of carbon atoms at their core to which two deoxysugars (forosamine and , , , tri-o-methylrhamnose, which are required for bioactivity) are attached. novel spinosyns have been prepared by biotransformation, using a genetically engineered strain of saccharopolyspora erythraea. a mixture of spinosyn a ( %) and d ( %) (spinosad) is being produced through fermentation and was introduced to the market in for the control of chewing insects on a variety of crops. spinosyn formulations were recently approved for use on organic crops and for animal health applications. recently, a new naturally occurring series of insect-active compounds was discovered from a novel soil isolate, saccharopolyspora pogona nrrl . the culture produced a unique family of over new spinosyns. they have a butenyl substitution at the position on the spinosyn lactone and are named butenyl-spinosyns or pogonins. herbicides are chemicals marketed to inhibit or interrupt normal plant growth and development. they are widely used in agriculture, industry and urban areas for weed management. approximately kinds of weeds are widely distributed in the world; yield losses caused by kinds of weeds are approximately . % of total crop production every year. herbicides provide cost-effective weed control with a minimum of labor. most are used on crops planted in large acreages, such as soy, cotton, corn and canola. there are numerous classes of herbicides with different modes of action, as well as different potentials for adverse effects on health and the environment. over the past century, chemical herbicides, used to control various weeds, may have caused many serious side effects, such as injured crops, threat to the applicator and others exposed to the chemicals, herbicide-resistant weed populations, reduction of soil and water quality, herbicide residues and detrimental effects on non-target organisms. for example, alachlor and atrazine were reported to cause cancer in animal tests. with increasing global environmental consciousness, bioherbicides, which are highly effective for weed control and environmentally friendly as well, are very attractive both for research and for application. microbial herbicides can be divided into microbial preparations (microorganisms that control weeds) and microbially derived herbicides. the first microbial herbicide was independently discovered in germany and japan. in , the zähner group in germany isolated phosphinothricin tripeptide, a peptide antibiotic consisting of two molecules of l-alanine and one molecule of the unusual amino acid l-phosphinothricin; that is, n( [hydroxyl(methyl)phosphinoyl]homoalanyl)alanylalanine. they isolated it from streptomyces viridochromogenes as a broad-spectrum antibacterial including activity against botrytis cinerea. in japan, it was discovered at the meiji seiki laboratories in from s. hygroscopicus and named bialaphos. the bioactive l-phosphinothricin is a structural analog of glutamic acid, acting as a competitive inhibitor of glutamine synthetase, and has bactericidal (gram-positive and gram-negative bacteria), fungicidal (b. cinerea) and herbicidal properties. glufosinate (dl-phosphinothricin) (without ala-ala) was developed as a herbicide. therefore, the agent acts as a herbicide with or without ala-ala. bialaphos has no influence on microorganisms in the soil and is easily degraded in the environment, having a half-life of only h. this low level of environmental impact is of great interest to environmentalists. in , the global animal health market was valued at us$ billion, of which % was derived from parasiticides. parasites are organisms that inhabit the body and benefit from a prolonged, close association with the host. antiparasitics are compounds that inhibit the growth or reproduction of a parasite; some antiparasitics directly kill parasites. in general, parasites are much smaller than their hosts, show a high degree of specialization for their mode of life and reproduce more quickly and in greater numbers than their hosts. classic examples of parasitism include the interactions between vertebrate hosts and such diverse animals as tapeworms, flukes, plasmodium species and fleas. parasitic infections can cause potentially serious health problems and even kill the host. parasites mainly enter the body through the mouth, usually through ingestion of tainted food or drink. this is a very common problem in tropical areas, but is not limited to those regions. there are varieties of parasites in four major categories: protozoa, trematoda, cestoda and nematoda. the major groups include protozoans (organisms having only one cell) and parasitic worms (helminths). each of these can infect the digestive tract, and sometimes two or more can cause infection at the same time. the who reported that approximately % of the world's population is infected with roundworms. in addition, a major agricultural problem has been the infection of farm animals by worms. the predominant type of antiparasitic screening effort over the years was the testing of synthetic compounds against nematodes, and some commercial products did result. certain antibiotics were also shown to possess antihelmintic activity against nematodes or cestodes, but these failed to compete with the synthetic compounds. although merck had earlier developed a commercially useful synthetic product, thiabendazole, they had enough foresight to examine microbial broths for antihelmintic activity, and found a non-toxic fermentation broth that killed the intestinal nematode nematosporoides dubius in mice. the streptomyces avermitilis culture, isolated by Ō mura and coworkers at the kitasato institute in japan, produced a family of secondary metabolites (eight compounds) with both antihelmintic and insecticidal activities. these compounds, named 'avermectins,' are pentacyclic, -membered macrocyclic lactones, that harbor a disaccharide of the methylated sugar, oleandrose, with exceptional activity against parasites, especially nemathelminthes (nematodes) and arthropod parasites ( times higher than any known synthetic antihelmintic agent). surprisingly, avermectins lack activity against bacteria and fungi, do not inhibit protein synthesis and are not ionophores. instead, they interfere with neurotransmission in many invertebrates, causing paralysis and death by neuromuscular attacks. the annual market for avermectins surpasses us$ billion. they are used against both nematode and arthropod parasites in sheep, cattle, dogs, horses and swine. a semisynthetic derivative, , -dihydroavermectin b ('ivermectin') is times more active than thiabendazole and is a commercial veterinary product. the efficacy of ivermectin has made it a promising candidate for the control of human onchocerciasis and human strongyloidiasis. another avermectin, called doramectin (or cyclohexyl avermectin b ), produced by 'mutational biosynthesis' was commercialized for use by food animals. a semisynthetic monosaccharide derivative of doramectin called selamectin is the most recently commercialized avermectin, and is active against heartworms (dirofilaria immitis) and fleas in companion animals. although the macrocyclic backbone of each of these molecules (ivermectin, doramectin and selamectin) is identical, there are different substitutions at pharmacologically relevant sites such as c- , c- , c- , and c- . the avermectins are closely related to the milbemycins, a group of non-glycosidated macrolides produced by s. hygroscopicus subsp. aureolacrimosus. these compounds possess activity against worms and insects. coccidiostats are used for the prevention of coccidiosis in both extensively and intensively reared poultry. coccidiosis is the name given to a common intestinal disease caused by the invading protozoan parasites of the genus eimeria that affects several different animal species (cattle, dogs, cats, poultry, etc.). the major damage is caused by the rapid multiplication of the parasite in the intestinal wall and the subsequent rupture of the cells of the intestinal lining, leading to high mortality and severe loss of productivity. coccidia are obligate intracellular parasites that show host specificity; only cattle coccidia will cause disease in cattle; other species-specific coccidia will not. for many years, synthetic compounds were used to combat coccidiosis in poultry; however, resistance developed rapidly. a solution came on the scene with the discovery of the narrow-spectrum polyether antibiotic monensin, which had extreme potency against the coccidian. made by streptomyces cinnamonensis, monensin led the way for additional microbial ionophoric antibiotics, such as lasalocid, narasin and salinomycin. all are produced by various streptomyces species. they form complexes with the polar cations k + , na + , ca + and mg + , severely affecting the osmotic balance in the parasitic cells and thus causing their death. the widespread use of anticoccidials has revolutionized the poultry industry by reducing the mortality and production losses caused by coccidiosis. of great interest was another extremely valuable application of monensin; that is, growth promotion in ruminants. synthetic chemicals had been tested for years to inhibit wasteful methane production by cattle and sheep and increase fatty acid formation (especially propionate) to improve feed efficiency; however, they failed. the solution was monensin, which became a major success as a ruminant growth enhancer. for more than years, certain antibiotics have been used in foodanimal production to enhance feed utilization and weight gain. from a production standpoint, feed antibiotics have been consistently shown to improve animal weight gain and feed efficiency, especially in younger animals. these responses are probably derived from an inhibitory effect on the normal microbiota, which can lead to reduced intestinal inflammation and improved nutrient utilization. pigs in the usa are exposed to a great variety of antibiotics. these include b-lactam antibiotics (including penicillins), lincosamides and macrolides (including erythromycin and tetracyclines). all these groups have members that are used to treat infections in humans. in addition, bacitracin, flavophospholipol, pleuromutilins, quinoxalines and virginiamycin are utilized as growth stimulants. flavophospholipol and virginiamycin are also used as growth promoters in poultry. as described above, cattle are also exposed to ionophores such as monensin to promote growth. the animal health institute of america has estimated that without the use of growth-promoting antibiotics, the usa would require an additional million chickens, million more cattle and million more pigs to reach the levels of production attained by the current practices. considering that animal health research and the development of new anti-infective product discovery have decreased, the discovery of new antibiotics has decreased over the past years, with few new drug approvals. therefore, it will be incumbent on veterinary practitioners to use the existing products in a responsible manner to ensure their longevity. it remains to be seen what effects the dearth of new antibiotics for veterinary medicine will have on the future practice of veterinary medicine, production agriculture, food safety and public health. since the eu decision to prohibit antibiotic use for foodanimal growth promotion, four antibiotic growth promoters have been banned, including the macrolide drugs tylosin and spiramycin. although macrolides are no longer formally used as 'growth promoters,' their use under veterinary prescription has risen from tons in to tons in , which suggests that more of them are being used now than before the prohibition. it is well known that the most effective route for feeding is via the gastrointestinal tract. many critically ill patients who accept early feeding improve their health. in some post-operative patients, gastric stasis and excessive volumes in the stomach increase the risk of aspiration and subsequent pneumonia. on account of the importance of achieving early and adequate nutritional intake, it is common practice in many intensive care units to use drugs to improve gastrointestinal motility. erythromycin is a macrolide antibiotic with a broad spectrum of activity. it is well recognized that when prescribed, either intravenously or orally, it causes side effects, such as diarrhea, nausea and vomiting. these side effects are, in part, due to the action of erythromycin at motilin receptors in the gut. this makes this antibiotic very attractive to be used in ill patients with gastrointestinal motility problems. there have been some developments on erythromycin analogs that lack antibiotic action but retain action at motilin receptors. these have been named 'motilides.' , recently, an orally active erythromycinderived motilin receptor agonist (mitemcinal) has been tested in patients with idiopathic and diabetic gastroparesis. in both cases, an improvement of gastroparetic symptoms was observed. the -year contribution of microorganisms to medicine and agriculture has been overwhelming. however, antibiotic resistance in microbes has created a dangerous situation and the need for new antibiotics is clear. unfortunately, most of the large pharmaceutical companies have abandoned the search for new antimicrobial compounds. owing to the economics, they have concluded that drugs directed against chronic diseases offer a better revenue stream than do antimicrobial agents, as for the latter the length of treatment is short and government restriction is likely. some small pharmaceutical and biotechnology companies are developing antibiotics, but most depend on venture capital rather than sales income, and with the present regulations, they face huge barriers to enter the market. these barriers were raised with the best intentions of ensuring public safety, but will have the opposite effect if they terminate antibiotic development while resistance continues to increase. however, there are some bright possibilities. one of the most promising is the utilization of uncultivated microorganisms. considering that % of the bacteria and % of the fungi have not been cultivated in the laboratory, putting efforts into finding means to grow such microorganisms are proceeding and succeeding. furthermore, researchers are now extracting bacterial dna from soil and marine habitats, cloning large fragments into, for example, bacterial artificial chromosomes, expressing in a host bacterium and screening the library for new antibiotics. this metagenomic effort is allowing access to a vast untapped reservoir of genetic and metabolic diversity, , which could result in the discovery of new and useful natural products. in addition to these two relatively new techniques, the chemical and biological modification of old antibiotics could still supply new and powerful drugs. these comments also apply to non-antibiotics such as antitumor agents and other microbial products. bioactive microbial metabolites. a personal view natural products 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in transfer of a disaccharide during biosynthesis of the antitumor drug mithramycin glut in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice improved production of pentostatin and identification of fermentation cometabolites pentostatin in t-non-hodgkin's lymphomas: efficacy and effect on cd + t lymphocytes cleavage behavior of calicheamicin gamma and calicheamicin t approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia study on the preparation and regeneration of protoplast from taxol-producing fungus nodulisporium sylviforme natural products as sources of new drugs over the last years epothilons a and b: antifungal and cytotoxic compounds from sorangium cellulosum (myxobacteria): production, physico-chemical and biological properties epothilones, a new class of microtubulestabilizing agents with a taxol-like mechanism of action activities of the microtubule-stabilizing agents epothilones a and b with 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with fk dosage, fk level and steroid following primary orthotopic liver transplant use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis mevinolin, a highly potent competitive inhibitor of hydroxylmethylglutaryl-coenzyme a reductase and a cholesterol-lowering agent a two-component-type cytochrome p- monooxygenase system in a prokaryote that catalyzes hydroxylation of ml- b to pravastatin, a tissue-selective inhibitor of -hydroxy- -methylglutaryl coenzyme a reductase a new hydroxylase system in actinomadura sp. cells converting compactin to pravastatin production and purification of statins from pleurotus ostreatus (basidiomycetes) strains evaluation and development of spinosyns to control ectoparasites on cattle and sheep engineered biosynthesis of novel spinosyns bearing altered deoxyhexose substituents butenyl-spinosyns, a natural example of genetic engineering of 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macrolide antibiotics. structure determination of milbemycins d polyether antibiotics: versatile carboxylic acid ionophores produced by streptomyces the determination of anticoccidial drugs (nicarbazin, lasalocid, monensin, salinomycin and narasin) in animal livers and eggs by liquid chromatography linked with tandem mass spectrometry (lc-ms-ms) the role of enteric antibiotics in livestock production (national association for crop production and animal health antibiotics as growth promotants: mode of action antibiotic resistance back in the news antibiotic development pipeline runs dry the future of anti-infective products in animal health the european ban on growth-promoting antibiotics and emerging consequences for human and animal health bioactive metabolites of em and em , erythromycin derivatives having strong gastrointestinal motor stimulating activity erythromycin as a gastrointestinal prokinetic agent clinical trial: effect of mitemcinal (a motilin agonist) on gastric emptying in patients with gastroparesis-a randomized, multicentre, placebocontrolled study the need for new antibiotics isolating 'uncultivable' microorganisms in pure culture in a simulated natural environment fulfilling the promise of biotechnology new antibiotics from bacterial natural products we thank beatriz ruiz and marco a ortiz for their assistance during the development of this review. key: cord- -q j vy u authors: jefferies, sarah; french, nigel; gilkison, charlotte; graham, giles; hope, virginia; marshall, jonathan; mcelnay, caroline; mcneill, andrea; muellner, petra; paine, shevaun; prasad, namrata; scott, julia; sherwood, jillian; yang, liang; priest, patricia title: covid- in new zealand and the impact of the national response: a descriptive epidemiological study date: - - journal: lancet public health doi: . /s - ( ) - sha: doc_id: cord_uid: q j vy u background: in early , during the covid- pandemic, new zealand implemented graduated, risk-informed national covid- suppression measures aimed at disease elimination. we investigated their impacts on the epidemiology of the first wave of covid- in the country and response performance measures. methods: we did a descriptive epidemiological study of all laboratory-confirmed and probable cases of covid- and all patients tested for severe acute respiratory syndrome coronavirus (sars-cov- ) in new zealand from feb to may , , after which time community transmission ceased. we extracted data from the national notifiable diseases database and the national sars-cov- test results repository. demographic features and disease outcomes, transmission patterns (source of infection, outbreaks, household transmission), time-to-event intervals, and testing coverage were described over five phases of the response, capturing different levels of non-pharmaceutical interventions. risk factors for severe outcomes (hospitalisation or death) were examined with multivariable logistic regression and time-to-event intervals were analysed by fitting parametric distributions using maximum likelihood estimation. findings: cases were detected over the study period, including ( · %) hospital admissions and ( · %) covid- deaths. the estimated case infection rate per million people per day peaked at · ( % ci · – · ) during the -day period of rapid response escalation, declining to · ( · – · ) in the start of lockdown and progressively thereafter. ( %) cases were imported or import related, tending to be younger adults, of european ethnicity, and of higher socioeconomic status. ( %) cases were linked to outbreaks. severe outcomes were associated with locally acquired infection (crude odds ratio [or] · [ % ci · – · ] compared with imported), older age (adjusted or ranging from · [ · – · ] for – year olds to · [ · – · ] for people aged ≥ years compared with – year olds), aged residential care residency (adjusted or · [ · – · ]), and pacific peoples (adjusted or · [ · – · ]) and asian ( · [ · – · ]) ethnicities relative to european or other. times from illness onset to notification and isolation progressively decreased and testing increased over the study period, with few disparities and increasing coverage of females, māori, pacific peoples, and lower socioeconomic groups. interpretation: new zealand's response resulted in low relative burden of disease, low levels of population disease disparities, and the initial achievement of covid- elimination. funding: ministry of business innovation and employment strategic scientific investment fund, and ministry of health, new zealand. there is an international imperative to provide evidence of the effectiveness of non-pharmaceutical interventions against covid- . early evidence in asia, including china, singapore, and south korea, showed covid- control using combinations of movement restrictions, physical distancing, hygiene practices, and intensive case and contact detection and management. [ ] [ ] [ ] the who-china mission recommended decisive government leadership to rapidly enhance surveillance and apply riskbased non-pharmaceutical interventions with effective population engagement. however, it was unclear how well this could be implemented in societies with little experience of successfully containing a novel respiratory virus. as evidence emerged that the unique nature of severe acute respiratory syndrome coronavirus (sars-cov- ) required distinct strategic approaches, new zealand moved from a response guided by national influenza pandemic planning to a covid- -tailored approach focusing on suppression (stopping sars-cov- commu nity spread) over mitigation (slowing down transmission), with a goal of covid- elimination, to reach very low or zero covid- incidence. risk-infor med border restrictions were implemented ahead of who advice before the first local case of covid- was con firmed on feb , . graduated suppression strategies were then applied, escalating to national lock down (stay-at-home order with few exemptions) within days. this response has international relevance, particularly for other island nations, high-income and western settings, and countries with ethnic and social health inequities. new zealand is a high-income remote pacific island state of nearly million people, with an ageing population and diverse ethnic structure: approximately % indigenous māori, % pacific peoples, % asian, and % european or other. inequitable morbidity and mortality for māori and pacific peoples, seen during previous influenza pandemics, continue for many communicable diseases today. covid- ethnic and social disparities have been observed overseas. , new zealand's response sought to prevent covid- disparities and minimise transit of infection to lower-income pacific countries. here, we investigate the impact of national suppression strategies on the epidemiology of the first wave of covid- in new zealand and measures of response performance. this descriptive epidemiological study examined a cohort of all confirmed and probable covid- cases and all people tested for sars-cov- infection in new zealand up to may , , which marked the easing of the most restrictive non-pharmaceutical interventions, after which community transmission ceased. national covid- case definitions applied. confirmed cases required laboratory definitive evidence (ie, sars-cov- detection by validated molecular test). probable cases were close contacts of confirmed cases with clinically compatible presentations where sars-cov- testing was incon clusive and other causes excluded. new zealand's com municable disease surveillance and response capabilities have been recently described and details on the four national covid- alert levels, their associated non-pharmaceutical interventions, and test and trace guidance have been published. , key features of the response timeline are outlined in the panel and figure , including nonpharmaceutical interventions required by alert levels and key surveillance changes. the speed of new zealand's alert level escalation (from alert level to between march and march , ) prevents assessment of individual alert levels on study outcomes. therefore, we considered the effects of national covid- suppression strategies over five phases. phase evidence before this study to identify international epidemiological studies of the effectiveness of non-pharmaceutical interventions on covid- containment and population outcomes, systematic searches of medline and pubmed were undertaken on july , , for peerreviewed articles published since jan , , using the following keywords: "novel coronavirus" or "ncov" or "covid- " or "severe acute respiratory syndrome coronavirus " or "sars-cov- "; and "epidemiolog*" or "public health strateg*" or "reproduction number" or "health loss" or "population impact*" or "effectiveness". of articles identified, were included. among these, three were in high-income democratic asian settings, seven in western settings, and two examined multiple international settings. escalation of non-pharmaceutical interventions including movement restrictions (travel bans or physical distancing) were effective in covid- mitigation or suppression to varied extents. we use highly complete, prospectively collected national covid- case and testing datasets to comprehensively describe new zealand's initial public health response to covid- . the response was notable for its speed and intensity (including border closure, rapid implementation of national lockdown, and surveillance enhancements) in a high-income, western setting with little previous experience of containing novel respiratory pathogens. this is the first study to our knowledge to assess the impacts of national or subnational non-pharmaceutical intervention escalation and de-escalation decisions on the distribution, transmission patterns, and severity of covid- , and the attainment of an explicit national goal of covid- elimination. new zealand's experience describes the multifaceted components of a national response as a feasible route to covid- elimination, particularly in other high-income or island settings. the study supports who recommendations for timely decisive government leadership for evidence-informed, risk-based escalation and de-escalation decisions combining rigorous case detection, isolation, contact tracing, and quarantine measures with population education and engagement. further research is needed to understand the wider cost benefits of this response. capacities including imple menting managed quarantine facilities for returning citizens and residents who could not safely self-isolate; and mandatory state-managed quarantine for all returning travellers (april ). phase was the second half of lockdown, covering april - , during which alert level continued and there were further increases in sars-cov- testing, including the first asymptomatic population survey (april ), before any decisions to change alert level. finally, phase was the de-escalation to alert level (april ), covering april -may , which included easing of population movement restrictions (eg, small gatherings up to ten people permitted). further population testing surveys were done before de-escalation to alert level on may . covid- became legally notifiable from jan , . suspected, probable, and confirmed case data were prospectively recorded on episurv, the national notifiable diseases database, using a standardised covid- case report form. all confirmed and probable case data were extracted on june , , including age, sex, location, new zealand index of deprivation (nzdep) quintile (where quintile is least socioeconomically deprived and quintile most deprived), travel history, occupation, basis for case detection, course of infection or illness, underlying conditions, link to a confirmed case or outbreak, and notification and confirmation dates. selfdetermined ethnicity was identified by linkage to the national patient demographics dataset. ethnicity was grouped by prioritised classification in order of māori, pacific, asian, and european or other, with the remaining cases classified as unknown. results of all sars-cov- molecular tests were extracted on june , , from Éclair, the national sars-cov- test results repository, with the following metadata: age, sex, linked prioritised ethnicity, district health board (dhb) location, and nzdep quintile. ethical approval for this study was obtained from the university of otago human ethics committee (health; hd / ). cases were assigned to the five phases in two ways to assess different impacts. first, cases were assigned to a phase on the basis of the estimated date of sars-cov- infection (ie, the exposure period), defined as occurring one incubation period before symptom onset (or notification date, if data on symptom onset were unavailable). uncertainty in incubation period was incorporated by replicate sampling (n= ) from a weibull distribution with means and ses pooled across replicates. assigned exposure period was then used to assess the impacts of non-pharmaceutical intervention phases on disease transmission and the characteristics of cases affected. the estimated average daily incidence of new zealandacquired case infection was calculated as the number of non-imported cases divided by the number of days in the phase and the national estimated population size. case counts, cumulative incidence, relative risks, and prevalence of demographic characteristics were compared by phase and by disease transmission types. transmission types were either outbreak (linked cases extending outside of a single household) or household cluster (cases living in the same household), and infection source was defined as imported (international travel within days of onset), import related (epidemiological link to an imported case), or locally acquired (no international travel within days and no link to an import-related case). characteristics of cases with severe disease outcomes (hospitalisation or death) were compared with non-severe cases. due to the low number of deaths that occurred (n= ), a separate analysis of mortality as an outcome was not done. second, for analyses of response performance, cases were assigned to a phase on the basis of the earliest date of evidence of infection (ie, the presentation period), defined as the date of illness onset (or notification date, if data on illness onset were unavailable). basis for case detection, physical distancing is enforced, additional precautions are encouraged for higher-risk groups (eg, people aged > years) when leaving home, and specific gatherings (eg, weddings) are permitted if no more than people. population is asked to stay within so-called bubbles (comprising household close contacts) that can include additional support (eg, carers) and encouraged to work from home, businesses must not physically interact with public, public venues are closed, no gatherings of more than ten people are allowed, telehealth services are encouraged, and only essential inter-regional travel is permitted. population is required to stay at home except for essential reasons (eg, short periods of exercise), businesses are closed unless offering essential services (eg, supermarkets), educational facilities and public venues are closed, and health-care services are reprioritised. a communication wellbeing campaign entitled getting through together is launched. testing incidence and positivity, and time-to-event intervals were calculated by phase using the presentation period. time-to-event intervals were average days from illness onset to notification, isolation, or hospitalisation dates. international arrival numbers, government response stringency index values, and population mobility changes were summarised for new zealand. the government response stringency index is a composite indicator measuring the strictness of government policy responses to covid- . population mobility changes were calculated using mobility data, with daily observed local resident mobility compared against median estimates for each weekday derived from a -week baseline (feb -march , ) to calculate percentage changes. rates and proportions were calculated with % cis assuming poisson and binomial distributions, respectively. new zealand population projections produced by stats nz for the ministry of health were used in denominators. risk factors for severe outcomes among cases were examined using logistic regression to estimate odds ratios (ors) and % cis. crude ors were calculated for age, sex, source of infection, and exposure phase variables. due to confounding by age, all other ors were adjusted for at least age and sex. aged residential care (arc) is an important setting for covid- outbreaks internationally, and there is potential error in our socio economic status measure for arc residents because it is based on arc facility location. therefore, to assess the impact of key demographic variables on risk of severe outcomes, multivariable analysis esti mated ors for age, sex, ethnicity, and socioeconomic deprivation including adjustment for arc residency and the presence of at least one underlying condition. there were insufficient data for precise estimates of risk associated with individual underlying conditions, so multivariable analyses were done only for conditions with at least total observations. key time-to-event intervals were analysed by fitting parametric distributions using maximum likelihood estimation. uncertainty intervals (uis) for key parameters were calculated using bootstrapping techniques. sensitivity analysis of the inclusion of probable cases (standard national reporting practice) and exposure period based on notification date for cases was assessed by repeating key study analyses with their exclusion. r (version · . ) and stata (version ) were used for statistical analyses. the funders of this study had no role in the study design, data analysis, data interpretation, or writing of the report. the corresponding author had full access to all of the data and final responsibility for the decision to submit for publication. cases of covid- were detected in new zealand presenting from feb to may , , of which ( %) were confirmed and ( %) probable ( figure ; table ). this was a cumulative incidence of · cases ( % ci · - · ) per million people. ( · %) people with covid- were admitted to hospital, ten admitted to intensive care ( · %), and ( · %) died (table ) . the estimated case infection rate per million people per day peaked in phase at · ( · - · ) followed by a % decrease to · ( · - · ) in phase (the first half of lockdown), progressively declining thereafter. the main source of infection was overseas acquisition, with the proportion attributable to importation declining from lockdown (ie, from phase onwards). the results of sensitivity analysis with the exclusion of probable cases are shown in the appendix (pp - ), with no major impacts on study findings. demographic characteristics were influenced by infection source, with ( %) imported and importrelated cases, and by outbreak settings (table ; figure ). covid- incidence was lowest in children for all sources (table ) . overall, cases were predominantly female, aged - years, of european or other ethnicity, and had higher socioeconomic status ( % in nzdep quintiles - ). people of māori ethnicity had the second-highest rate of import-related disease after people of european or other ethnicity (table ) , with ( %) māori cases in this group linked to new zealand's largest outbreak (see wedding in figure ). locally acquired cases showed female predominance, higher incidence among asian and pacific peoples, and distribution across deprivation quintiles (table ) . these characteristics, as well as major geographical trends, were evident in the demographics of major locally acquired outbreaks (figure ). cases were detected throughout new zealand, with the highest incidence per population being found in southern ( · , % ci · - · ), waikato ( · , · - · ), and waitemata ( · , · - · ) . travel restriction start dates are highlighted, which include entry restrictions to foreign nationals from specified countries, requirement for all remaining incoming travellers to isolate for days, and border closures to all but new zealand citizens or residents. panel b shows daily sars-cov- molecular testing counts and daily test positivity (for days with ≥ tests) and major national covid- surveillance changes. sars-cov- =severe acute respiratory syndrome coronavirus . *expanded to include non-febrile presentations of acute respiratory infection (shortness of breath, cough or sore throat, with or without fever), and testing of asymptomatic household contacts. †removal of epidemiological criteria (travel to covid- -affected areas or close contact with a case) as a requirement (with clinical presentations) and expanded clinical criteria to include anosmia and coryza. percentages shown are percentages of the total cases unless indicated otherwise. icu=intensive care unit. sars-cov- =severe acute respiratory syndrome coronavirus . *cases were assigned to study exposure periods by sampling incubation periods from a weibull distribution before illness onset (or notification date for cases with no illness onset data, of whom were asymptomatic). †new zealand-acquired infection; excludes imported cases. ‡ of these cases were the first cases to emerge in the community with no known source. §includes airline crew and other frontline service workers (eg, police). ¶outcomes are not mutually exclusiveie, cases could be assigned to more than one of hospitalisation, icu admission, and death. covid- was reported as the primary cause of death on the covid- case report form for all deceased cases. ||cases were assigned to study presentation periods by date of illness onset (or notification date if no illness onset data). **includes asymptomatic self-referral for testing outside of case definition or contact tracing protocol. popu lation structure, asian or pacific peoples were disproportionately affected in eight out breaks and māori in the largest (figure ). among ( %) cases linked to covid- household clusters, only nine ( · %) cases in people younger than years of age were the first cases in their household. case symptoms are summarised in the appendix (p ). only ( %) of cases presented with cough and fever. severe outcomes were associated with older ages: multivariable adjusted ors ranged · ( % ci · - · ) for - year olds to · ( · - · ) for people aged years or older, compared with - year olds (appendix pp - ). after age-sex adjustment, having reported at least one underlying condition was associated with severe outcomes (or · [ · - · ]) as was arc residency ( · [ · - · ]; appendix pp - ). there was no clear association of lower socioeconomic status with severe outcomes after adjusting for arc residency, as well as for age, sex, ethnicity, and having at least one underlying condition (appendix pp - ). higher odds of severe outcomes were associated with pacific peoples ( · [ · - · ]) and asian ( · [ · - · ]) ethnicity versus european or other ethnicity after multivariable adjustment (appendix pp - ), although no asian or pacific peoples died. higher odds of severe outcomes associated with locally acquired infection ( · [ · - · ] compared with imported) and exposure in later phases ( · [ · - · ] in phase compared with phase ) is explained by the timing and occurrence of locally acquired outbreaks in vulnerable-population settings (eg, arc; figure ; appendix pp - ). among covid- deaths, the mean age was · years (sd · ; range - ), ( %) were male, ( %) were of european or other ethnicity, two ( %) were māori, and ( %) lived in arc facilities. ( %) cases had at least one underlying condition. initially, cases were mostly identified through clinical health-care presentations, but predominantly through contact tracing from phase onwards (table ) . sars-cov- tests were done up to may , with a -times increase in testing incidence from phase to phase , and less than % national daily test positivity from march ( figure ; table ) . a dramatic drop in international passenger arrivals and considerably reduced population mobility were observed from phase (appendix p ). testing increased over the study period among all demographic groups (figure ; appendix pp - ). females had consistently higher testing rates than males (figure ). in phase , testing rates were highest in people of asian ethnicity, adults aged - years, and people of higher socioeconomic status (figure ; appendix pp - ). subsequently, pacific peoples, adults aged - years, and people of lower socioeconomic status had higher rates. people younger than years of age had lower testing rates in every phase (appendix pp - ). key time-to-event intervals declined by phase, except for time to hospitalisation where numbers were too small to stratify (median days [iqr to ; range to ]; appendix pp - , ). between phases and , the average time from illness onset to notification reduced from · days ( % ui · to · ) to · days ( · to · ) and average isolation intervals from · days ( · to · ) to − · days (− · to − · ) days, where negative days represent isolation before illness onset (appendix p ). small counts in phase prevented maximum likelihood estimations. numbers were also too small for phasebased stratification by source of infection or basis for case detection. sensitivity analysis with the exclusion of probable cases found no significant differences in timeliness, except for a shorter average onset to notification interval in phase (appendix pp - ). new zealand experienced one of the lowest cumulative case counts, incidence, and mortality among higherincome countries in its first wave of covid- following early implementation and rapid escalation of national covid- suppression strategies. , new zealand effectively achieved control with progressive, riskinformed border closures reducing the burden of imported disease driving the epidemic. this was followed, only days after first case confir mation, by a phase of rapid escalation of non-pharmaceutical interventions to national lockdown. this -day escalation phase had the highest average daily case infection rate during the study period. within weeks, lockdown was associated with a substantial reduction in daily case infection rate and improving response performance measures: the majority of cases were detected by contact tracing, and there were decreasing average times to case notification and isolation and increasing population testing with effective targeting of higher-risk groups. enhancements in response capacity also supported de-escalation decisions. the daily test positivity was less than % from march (day of lockdown), as recommended by who before easing of restrictions, and only cases of asymptomatic infection were detected despite routine testing of asymptomatic contacts, population testing surveys targeting asymptomatic and highrisk groups, and high testing rates by phase . moreover, despite full de-escalation to alert level on june , new zealand effectively eliminated covid- , as currently defined, to very low numbers detected at border quarantine facilities for an extended period. furthermore, rapid suppression of community transmission limited overall disease disparities for populations most vulnerable to severe outcomes. most cases were linked to imported cases, with predominant features of healthy travellers: younger adults, european ethnicity, and higher socioeconomic status. locally acquired disease was less common, but tended to reach more vulnerable populations (ie, older people, arc residents, and minority ethnic groups) and was associated with more severe outcomes. female case predominance in this group probably relates to the settings where locally acquired outbreaks occurred, including a girls' school, and arc facilities where residents and carers were more likely to be female, but is potentially influenced by testing bias. higher female testing incidence might reflect female predominance in certain high-risk groups targeted for testing, such as health-care workers, which is also considered a potential reason for slight female case predominance described in england. higher male mortality reported overseas was not seen in new zealand, , , and although the crude or for severe outcomes was slightly higher for males, this estimate was imprecise and did not persist after multivariable adjustment. in keeping with some international findings, children appeared to have had a lesser role in household transmission and outbreaks-even at a school-in new zealand, despite intensive testing of asymptomatic contacts. , however, with lower national testing rates in children, detection bias cannot be excluded. high-risk workers and indigenous māori people did not appear to be disproportionately affected in the first wave. rapid control of community transmission through mandatory physical distancing provided time to enhance the response, including prioritised testing of higher-risk groups, also ensuring that covid- did not overburden health system capacity. nonetheless, after adjustment for confounders, older people, arc residents, people reporting at least one underlying condition, and asian and pacific peoples were at higher risk of severe outcomes than other populations. these findings align with international risk associations. , , , , our study supports the ongoing need for the response to address systemic barriers, such as health-care access, to achieving equitable health outcomes for minority and higher-risk groups, particularly in the absence of elimination. there are contextual features of new zealand's experience that have implications for generalisability to other settings. new zealand's small, non-federated health system proved responsive, including rapid test development and early reprioritisation of health-care services, with readiness probably facilitated by delay in the first case arriving due to border measures. the pandemic's commencement during new zealand summer time with low seasonal respiratory infections meant an initially restricted testing resource could be more readily targeted. despite these advantages, there was some early undetected community transmission, with the first locally acquired case presenting on march when the national case definition targeted febrile illness, a less frequent feature of covid- in the new zealand cohort and overseas. in new zealand, only a low proportion of asymptomatic infection was detected relative to other countries despite widespread testing, and the low level of community transmission that occurred might have contributed to this. serological studies are required to quantify this further. new zealand's border response has implications for island states where borders can be more readily controlled. samoa and fiji, for example, also exercised early border closures to non-citizens and non-residents, aligning with strategies effective during the pandemic, and so far maintain zero or very low covid- counts. , while clearly effective in limiting disease importation, there remain questions about the costs and sustainability of these measures. although new zealand-based research before the pandemic suggested a net health economic benefit from complete border closure in a modelled pandemic scenario, the potential indirect health effects of the national response are under surveillance and the net impacts yet to be determined. cost-effectiveness analysis lay outside the scope of our study but focused research in this area is essential. furthermore, taiwan has shown that covid- control can be achieved in the absence of complete border closure, although using advanced technological systems and ongoing strict disease suppression strategies in a society that had already normalised some of these measures from previous novel virus exposures. , finally, the speed and intensity of the national response to limit the epidemic is unprecedented internationally; new zealand had the fastest trajectory to reach the highest country score in the government response stringency index. the observed impact of lockdown on inhibiting disease transmission aligns with reproductive number estimates for before and after lockdown produced for new zealand and other countries. , , it is likely this early, intense response, which also enabled relatively rapid easing while maintaining strict border controls, prevented the burden of disease experienced in other high-income countries with slower lockdown implementation, including australia, the uk, and italy-the latter initially taking mitigation approaches. [ ] [ ] [ ] integral to new zealand's response has been decisive governance, effective communication, and high population compliance-in an earthquake-prone country, communities and emergency management systems are primed for disaster response. , this study has methodological advantages. it uses two comprehensive national datasets: one employing standardised national case questionnaires prospectively applied to every notified case for the primary purpose of covid- surveillance, and the other recording every sars-cov- test done using nationally validated methodology. moreover, data were extracted for the study period in mid-june, enabling completeness, and preventing right censoring of the epidemic curve. furthermore, following the end of the study period, case numbers remained very low, including a -day period where no cases were notified. there are also limitations. it was not possible to differentiate impacts of individual non-pharmaceutical interventions due to the rapid and overlapping implementation of response measures. moreover, the relatively small case dataset has statistical limitations for comparative analyses. the categorisation of phases and presentation and exposure periods incorporated assumptions. in particular, the modelled incubation period applied to all cases was not derived from new zealand data and some cases might have been incorrectly assigned to an exposure period. misclassification of imported cases is also possible, although % of cases became symptomatic in phase within days of arrival from overseas. finally, as an observational study using surveillance data, results are prone to errors including inter-operator differences in defining and recording case data. notably, that cases were on average recorded as being isolated before symptom onset from phase onwards suggests that quarantine (or self-isolation) dates were reported. although the impacts of movement restrictions cannot be differentiated from the timeliness of case management here, this still measures response performance. in conclusion, our study indicates that early and intense implementation of national covid- suppression strategies have effectively altered the course of new zealand's epidemic and limited the burden of disease and inequities in this high-income democratic setting, initially achieving covid- elimination. this supports the who recommendations for timely decisive national leadership for evidence-informed, risk-based escalation and de-escalation decisions combining rigorous case detection, isolation, contact tracing, and quarantine measures with population education and engagement. further surveillance and research are needed to understand the cost benefits, particularly the indirect population health and social impacts, of this response. sj led study design with inputs from pp, nf, pm, np, jm, vh, and cm. cg and sj led data collection, with pm also obtaining data. cg, np, gg, sp, jsh, sj, jm, am, pm, and ly analysed the data and contributed to interpretations with all other authors. sj led the development of figures with pm. jsc and sj reviewed the literature. sj led manuscript writing, with all authors contributing to the final draft. np reports funding from glaxosmithkline, outside of the submitted work. all other authors declare no competing interests. all study data were extracted from the national databases episurv and Éclair, and can be obtained for research purposes by contacting data-enquiries@health.govt.nz and following the covid- data request process. evaluation of the effectiveness of surveillance and containment measures for the first patients with covid- in singapore report of the who-china joint mission on coronavirus disease (covid- ). geneva: world health organization covid- in south korea how will country-based mitigation measures influence the course of the covid- epidemic? report : impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand covid- health and disability system response plan. wellington: ministry of health differential mortality rates by ethnicity in influenza pandemics over a century disparities in the risk and outcomes of covid- racial disparity of coronavirus disease (covid- ) in african american communities joint external evaluation of ihr core capacities of new zealand: mission report: - new zealand covid- alert levels summary updated advice for health professionals: novel coronavirus (covid- ) nzdep : a new zealand index of deprivation hiso : ethnicity data protocols the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application statistics new zealand. provisional international travel statistics: daily arrivals and departures data oxford covid- government response tracker a leisurely look at the bootstrap, the jackknife, and cross-validation who. coronavirus disease (covid- ) situation report- association of public health interventions with the epidemiology of the covid- outbreak in wuhan, china high impact of covid- in long-term care facilities, suggestion for monitoring in the eu/eea covid- : we must not forget about indigenous health and equity protective effect of maritime quarantine in south pacific jurisdictions, - influenza pandemic economic evaluation of border closure for a generic severe pandemic threat using new zealand treasury methods response to covid- in taiwan: big data analytics, new technology, and proactive testing effective reproduction number for covid- in aotearoa new zealand. te pūnaha matatini the effect of large-scale anti-contagion policies on the covid- pandemic early analysis of the australian covid- epidemic the uk's public health response to covid- pandemic leadership: lessons from new zealand's approach to covid- · -· · -· · - · · -· · -· outbreak summaries show outbreak settings, number of linked cases, date range of illness onset, number of dhbs involved, female cases as percentage of total, median age (iqr), cases by ethnicity (māori, pacific peoples, european or other ethnicities, or unknown) as a percentage of total, percentage of total cases infected due to within household transmission, and percentage of cases identified as high-risk workers. household transmission excludes cases from household clusters that introduced sars-cov- to the household and any other cases in a household with symptom onset within day of the first case. dhb=district health board. sars-cov- =severe acute respiratory syndrome coronavirus . key: cord- -xo qzhna authors: breed, andrew c.; yu, meng; barr, jennifer a.; crameri, gary; thalmann, claudia m.; wang, lin-fa title: prevalence of henipavirus and rubulavirus antibodies in pteropid bats, papua new guinea date: - - journal: emerg infect dis doi: . /eid . sha: doc_id: cord_uid: xo qzhna to determine seroprevalence of viruses in bats in papua new guinea, we sampled bats at locations. we found a seroprevalence of % for henipavirus (hendra or nipah virus) and % for rubulavirus (tioman or menangle virus). notably, % of bats surveyed contained antibodies to both types of viruses, indicating concurrent or consecutive infection. to determine seroprevalence of viruses in bats in papua new guinea, we sampled bats at locations. we found a seroprevalence of % for henipavirus (hendra or nipah virus) and % for rubulavirus (tioman or menangle virus). notably, % of bats surveyed contained antibodies to both types of viruses, indicating concurrent or consecutive infection. t he genus henipavirus in the family paramyxoviridae contains highly lethal viruses, hendra virus (hev) and nipah virus (niv), both of which use pteropid bats as their main natural reservoir ( ) . the discovery of hev in australian fl ying foxes in ( ) marked the beginning of a new wave of research activities, which led to the association of bats with some of the most notable viral pathogens to emerge in recent history, including niv ( ), severe acute respiratory syndrome-like coronaviruses ( ), ebola virus ( ), and marburg virus ( ) . in addition to the henipaviruses, novel paramyxoviruses in the genus rubulavirus were discovered in australia and malaysia. menangle virus (menpv) was isolated in australia during a disease outbreak in pigs, with epidemiologic evidence suggesting the involvement of human patients as a result of pig-to-human transmission ( ) . tioman virus (tiopv) was isolated from bat urine collected on tioman island in malaysia and, although anti-tiopv antibodies were detected in residents of the island, its potential to cause disease in humans is unknown ( ) . several orthoreoviruses were also isolated from bats in australia and malaysia. pulau virus was isolated from bat urine collected on tioman island in ; it is closely relat-ed to the nelson bay virus (nbv) isolated from a pteropid bat in in australia ( ) . more recently, melaka virus and kampar virus, both closely related to viruses in the nbv species group, were isolated from human patients with respiratory symptoms; epidemiologic investigations strongly suggested they were the causative agents ( , ) . broome virus (brov), a new orthoreovirus species, was isolated from a sick little red fl ying fox (pteropus scapulatus) in in australia, but its disease-causing potential is unknown ( ) . this study was conducted in june to survey bats in papua new guinea to determine the presence of various known bat viruses and to assess the potential of these viruses to be transmitted to the bat populations in australia. a total of bats were caught at locations in papua new guinea ( figure; online appendix table, www.cdc. gov/eid/content/ / / -appt.htm). they were anesthetized by using a combination of ketamine and medetomidine at doses similar to those stated in a previous study ( ) . blood samples were held at room temperature for - hours and then serum separated by using centrifugation as required. serum samples were held at °c until they were shipped to the australian animal health laboratory. virus-specifi c antibodies were detected by using a variety of assays previously developed by our group at the australian animal health laboratory. for the henipaviruses, the luminex-based binding and inhibition assays ( ) were used for initial screening, and positive samples were confi rmed by virus neutralization test (vnt). only those with positive results in all assays are shown in the online appendix table. for tiopv and menpv, initial screening was conducted by using an elisa with purifi ed tiopv virion as antigen. elisa-positive samples were then confi rmed by vnt against each virus. for viruses in the nbv species group, a mixture of purifi ed recombinant sigma c proteins from nbv, pulau virus, melaka virus, and kampar virus was used as elisa antigen for initial screening. positive samples were then confi rmed by western blot against each of the recombinant proteins. for brov, initial screening was conducted by elisa using purifi ed virion as antigen; positive samples were confi rmed by immunofl uorescent antibody test on cells infected with brov. a summary of the results is presented in the online appendix table. seroprevalence for hev was % ( / ); for niv, % ( / ); tiopv, % ( / ); menpv, % ( / ); nbv-like viruses, % ( / ); and brov, % ( / ). the seroprevalence of the types of paramyxoviruses, hev/niv at % and tiopv/menpv at %, is high. the most striking fi nding is the presence of antibodies to both groups of viruses in % ( / ) of the samples. considering that vnt is a more specifi c and less sensitive assay, the actual positive rate could be > %. compared with results of the study conducted in madgascar ( ), in which / serum samples contained vnt-positive antibodies to both henipavirus and tiopv, our fi nding suggests extremely different paramyxovirus infection dynamics in bats in papua new guinea. whether these data suggest concurrent or consecutive infection is not clear. we anticipate that the use of pteropid immunoglobulin m-specifi c reagent (currently in development in our group) will clarify this question in the future. the positive rate for both groups of paramyxoviruses is much higher in p. conspicillatus bats (spectacled fl ying fox) from madang than dobsonia magna bats (bare-backed fruit bat) from bensbach. we believe this difference has more to do with the bat species than the geographic location. for henipaviruses, seroprevalence is slightly higher for niv than for hev, which is also consistent with the luminex inhibition assay showing a trend of slightly higher inhibition for niv than for hev (data not shown). this higher seroprevalence may suggest that henipaviruses circulating in papua new guinea are more niv-like than hev-like. however, in the absence of genetic sequence data, serologic fi ndings are inconclusive. in addition, for the rubulaviruses, seroprevalence is higher for menpv than for tiopv. this fi nding is noteworthy because our previous data indicated a one-way crossneutralization, with menpv antibodies failing to neutralize tiopv (g. crameri and j. barr, unpub. data). the results from this study suggest either that the main strain of bat rubulavirus(es) circulating in bats in papua new guinea is more closely related to menpv or that there are different strains circulating and the menpv-like are more dominant. although the overall seroprevalence for orthoreoviruses was much lower, the results nevertheless produced some useful information. first, the prevalence of % ( / ) of the nbv group viruses in d. magna bats at bensbach is not much different from the % ( / ) in p. conspicillatus bats at madang, indicating the nbv group of orthoreoviruses is present in bats of different species in papua new guinea. second, none of the serum samples was positive for both nbv and brov, which supports our previous conclusion that brov is a new species in the genus orthoreovirus and that no signifi cant cross-reactivity occurs between brov and orthoreoviruses of other species groups ( ) . in this study, a serologic survey was conducted for groups of viruses, from the family paramyxoviridae and from the genus orthoreovirus, family reoviridae. the surprising fi nding of a high prevalence of antibodies to both henipaviruses and tiopv/menpv in individual pteropid bats highlights the need for more structured studies to investigate the infection dynamics of zoonotic viruses in different bat populations across the world. it is not clear at this stage what factors are responsible for the vast difference in prevalence of antibodies to paramyxoviruses and orthoreoviruses. in the context of potential incursion of exotic bat viruses into australia, it is noteworthy that the bat rubulavirus(es) circulating in papua new guinea are more menpv-like (australia), whereas the papua new guinea henipavirus(es) seem to be more niv-like (asia). these fi ndings are consistent with those in indonesia ( ) and call for further molecular epidemiologic investigation to better assess the risk of niv entry into australia. emerging infectious diseases • www.cdc.gov/eid • vol. , no. , december fields virology isolation of hendra virus from pteropid bats: a natural reservoir of hendra virus bats are natural reservoirs of sars-like coronaviruses fruit bats as reservoirs of ebola virus isolation of genetically diverse marburg viruses from egyptian fruit bats probable human infection with a newly described virus in the family paramyxoviridae. the nsw expert group serological evidence of possible human infection with tioman virus, a newly described paramyxovirus of bat origin pulau virus; a new member of the nelson bay orthoreovirus species isolated from fruit bats in malaysia a previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans identifi cation and characterization of a new orthoreovirus from patients with acute respiratory infections broome virus, a new fusogenic orthoreovirus species isolated from an australian fruit bat experimental nipah virus infection in pteropid bats (pteropus poliocephalus) neutralization assays for differential henipavirus serology using biol-plex protein array systems henipavirus and tioman virus antibodies in pteropodid bats henipavirus in pteropus vampyrus bats we thank nime kapo and the national agriculture quarantine and inspection authority of papua new guinea for facilitating this work and bisai laba, chris leigh, and francis yakour for assistance with collection of samples.this work was supported in part by funding from the northern australia quarantine strategy program of the australian quarantine and inspection service and the australian biosecurity cooperative research center for emerging infectious disease.dr breed is a veterinary epidemiologist at the veterinary laboratories agency in addlestone, uk. his research interests include the epidemiology and ecology of wildlife, particularly viral zoonoses. key: cord- -onipxf z authors: wang, x.; zou, c.; xie, z.; li, d. title: public opinions towards covid- in california and new york on twitter date: - - journal: medrxiv : the preprint server for health sciences doi: . / . . . sha: doc_id: cord_uid: onipxf z background: with the pandemic of covid- and the release of related policies, discussions about the covid- are widespread online. social media becomes a reliable source for understanding public opinions toward this virus outbreak. objective: this study aims to explore public opinions toward covid- on social media by comparing the differences in sentiment changes and discussed topics between california and new york in the united states. methods: a dataset with covid- -related twitter posts was collected from march , to april , using twitter streaming api. after removing any posts unrelated to covid- , as well as posts that contain promotion and commercial information, two individual datasets were created based on the geolocation tags with tweets, one containing tweets from california state and the other from new york state. sentiment analysis was conducted to obtain the sentiment score for each covid- tweet. topic modeling was applied to identify top topics related to covid- . results: while the number of covid- cases increased more rapidly in new york than in california in march , the number of tweets posted has a similar trend over time in both states. covid- tweets from california had more negative sentiment scores than new york. there were some fluctuations in sentiment scores in both states over time, which might correlate with the policy changes and the severity of covid- pandemic. the topic modeling results showed that the popular topics in both california and new york states are similar, with "protective measures" as the most prevalent topic associated with covid- in both states. conclusions: twitter users from california had more negative sentiment scores towards covid- than twitter users from new york. the prevalent topics about covid- discussed in both states were similar with some slight differences. in december , a novel and contagious coronavirus disease of (covid- ) has been reported in china and continued spreading out massively. the cause of this pandemic is due to a novel coronavirus called sars-cov- . according to the centers for disease control and prevention (cdc), the coronavirus could transmit between persons through close contact [ ] . on january , , covid- became a public health emergency of international concern [ ] . by june , , the coronavirus has been confirmed in six continents with nearly nine million covid- cases. the number of confirmed cases in the u.s. has been grown rapidly since early march. on march , new york declared a state of emergency after confirmed cases, and since then, the confirmed cases continued increasing at an alarming rate. new york state was facing severe challenges in health care, including a shortage of protective gear and medical equipment, hospital overcrowding, and paramedic shortages. meanwhile, california, as the most populous state in the u.s., was also facing the viral transmission, but less severe than what ny faced. discussions about the covid- pandemic are widespread online, especially through social media, which offers powerful public platforms where people can share their opinions with large crowds. twitter is an online microblogging and networking platform, and users can post and all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint interact messages known as "tweets". in past few years, twitter data has been increasingly used for research. previous study had used twitter data to reveal insights from user-generated tweets about ebola through textual analytics [ ] . the outbreak of coronavirus in the u.s. has created an uproar in discussions about the pandemic on twitter. a recent research collected a dataset of million twitter posts using the keywords "coronavirus" and discussed the dynamics of coronavirus on twitter [ ] . however, little work has been reported on social media data analysis that focused on covid- in the united states, since its outbreak on march . with the growth of the number of confirmed covid- cases and the announcement of covid- related policies, mentions of coronavirus-related topics and sentiments might vary over time. it's important to understand how the perceptions of the pandemic related issues evolve over time, and whether they vary with different geolocations. thus, in this study, we aimed to investigate the differences in sentiments and public opinions towards the outbreak of covid- for twitter users between new york state and california state in the united states, and how these are related to the number of cases and policy changes. our study provides valuable information about public attitude changes over time towards the emergence and outbreak of covid- , which could guide future research on exploring public concerns towards the pandemic. we obtained covid- -related twitter posts from march , to april , , via twitter streaming api. to generate only covid- -related posts, we used a list of keywords for twitter streaming-"corona", "corona", "covid ", "covid ", "covid", "coronavirus", "coronavirus", "coronavirus", and "ncov". the dataset was then filtered by the same keyword all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint set to remove any unrelated posts. another filtering process was to remove the promotional and commercial posts. since "corona" is a beer brand in the market, it's possible that the discussions in the posts about corona were not related to the coronavirus. the keywords for filtering are "dealer", "deal", "supply", "beer", "drink", "drank", "drunk", "store", "promo", "promotion", etc. to identify tweets from california and new york, the last data filtering process is to separate tweets into two datasets -one dataset contains posts only from california state, another only from new york state, based on the geolocation information associated with each tweet. the keywords used to filter locations, such as "los angeles, ca", "monroe, new york", are scraped from wikipedia website (list of cities and towns) [ ] . to prevent from missing locations while filtering, all the county and city names are considered into the keyword lists. by converting itemset into data frames and dropping the duplicates, we removed any duplicated items that share the same id number. the number of confirmed covid- cases in california and new york states each day from march , to april , were downloaded from the website of point acres.com [ ]. in order to explore the trend of covid- -related tweets posted between march , and april , , we calculated the number of tweets by days and hours for each state. to convert the date into the correct time zone, we parsed the date time into readable date format with the corresponding time zone. we calculated the average number of tweets posted by each hour within a -hour period. the vader (valence aware dictionary and sentiment reasoner) was used for the sentiment analysis, which is a tool that is commonly used for sentiment analysis of social media data [ ] . all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint we applied the vadersentiment package in python to calculate the sentiment score for each tweet and calculated the average sentiment scores by each day and each hour. for the text in each post, we extracted the compound score, which is normalized between - (negative extreme) and + (positive extreme). we calculated the average sentiment score within each hour in a -hour period for days. in addition, a two-sample t-test was conducted to test whether there is a significant difference between average sentiment scores in california and new york based on the sentiment scores per minute. topic modeling is typically used to discover abstract "topics" in documents through statistical modeling [ ] . to understand the most frequent topics that twitter users were discussing about covid- , we applied latent dirichlet allocation (lda) for topic modeling analysis. to build the lda model, several steps were conducted: • remove noises -emails, newline, extra spaces, distracting single quote and urls • tokenization -split texts into sentences and words, lower case the words and remove punctuation • create bigram and trigram models -convert two or three words frequently occurring together in the document (eg. difficulty_breathing, magic_johnson, catching_feelings) • remove stop words downloaded from nltk, and make bigrams and trigrams • lemmatization using spacy -lemmatize the words to a normal form • create dictionary and corpus as lda input to identify the optimal number of topics, we calculated the coherence scores from topics to topics and considered the number of topics with the highest coherence score as the optimal number of topics. after building the lda model, we applied pyldavis to visualize the all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint information contained in the topic models. it's a python built-in package that helps understand the meaning of each topic, the prevalence of each topic, and the correlation among topics. according to sievert and shirley's study result, the optimal value of the weight parameter is . in the pyldavis method [ ] . in our analysis, we adjusted the parameter to . and extracted the top ten frequent words in each topic. the summary of each topic was manually conducted and discussed among all coauthors. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint a sentiment analysis was conducted to understand public attitudes toward the number of covid- cases and the policy changes. we calculated average sentiment scores for covid- tweets from california and new york between march , and april , . overall, both states had negative sentiment scores towards covid- . the average sentiment score for california was - . (standard error = . ), while for new york, it was - . (standard error = . ). a two-sample t-test showed that the difference in average sentiment scores between california and new york was significant (p-value < . ). the daily average sentiment scores in both new york and california varied over time ( figure ). in the -hour period, new york showed a clear peak on the hourly average sentiment score, with the highest sentiment score of - . at : am (supplemental figure ). in contrast, california did not show a clear peak. in addition, twitter users from both states showed more negative sentiments towards covid- from midnight to early morning. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint the lda topic modeling was applied to understand the general topics in covid- tweets. based on the coherence scores, we found that with new york data the optimal number of topics was while with california data it was . we then summarized each topic with top frequent words (table ) . all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint table as shown in table , topics discussed in covid- tweets in both new york and california were very similar, among which the most prevalent topic was "protective measures". in addition, (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint concerns about the covid- pandemic and government actions, such as "public concerns" and "government and policy", were other popular topics in both states. in this study, we showed that from march to april in , the number of covid- tweets in california was almost twice of that in new york. california had a significantly lower sentiment score towards covid- than new york. in addition, we showed that the sentiment scores towards covid- in both california and new york varied over time, and the policy announcements and number of confirmed cases might be the major drives for these sentiment changes. twitter users from both states discussed similar topics, with the "protective measures" as the most popular topic, followed by "pandemic's impact" and "government policy". while we showed that the sentiment scores varied over time in both california and new york, the highest and lowest sentiment scores correlated with some important policy announcements and the severity of covid- . on march , governor cuomo declared a state of emergency in new york, and the sentiment score on that day was the lowest (- . ). one possible explanation is that people expressed serious concerns about the covid- pandemic. the word "emergency", along with "sick", "leave", "business", "worker", suggests that people were worried about their businesses and not being able to work. meanwhile, on the same day, the average sentiment score in california was the lowest, which coincide with the policies including the largest school district was closed, and san francisco banned large group gatherings. another interesting observation is that on march , , the average sentiment scores in both states reached the highest point. the major event happened on that day was that a $ trillion coronavirus relief package was passed to address the economic impacts caused by the pandemic. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint it can be inferred that since the pandemic has forced a lot of people losing their jobs and not being able to maintain their livings, the announcement of relief bill could relieve some financial stresses, which led to less negative sentiment scores in both states. in addition, we found that the number of confirmed cases and deaths might correlate with the public's sentiment. for instance, on march , the number of confirmed cases in california reached [ ] ; on march , new york surpassed death tolls [ ] , and california surpassed death tolls [ ] . these numbers might be the drives for more negative sentiment scores in both states. since new york had much more confirmed cases and deaths than california in march , we would expect that the average sentiment score in new york would be lower than in california. however, our results showed that california had a lower sentiment score (- . ) than new york (- . ), and the difference is significant. one explanation for this is that on march , , new york began gathering ventilators across the state. the federal disaster assistance might bring people who were in pessimistic situations some hopes. a recent research by wallethub about the unemployment rate showed that new york had a . % increase in the unemployment claims since the start of the covid- pandemic, and california had a . % increase, much less than new york [ ] . thus, the $ trillion relief bill happened on march could provide people in new york financial support more significantly. another reasonable speculation could be that as the most populous state in the u.s., california people might be more worried about the potential high infection rate. our result on topic modeling analysis showed that there was no major difference between the topics discussed in california and new york. however, the popularity of each topic was different between two states. the topic that had the highest token percentage in both states was related to protective measures. they shared the same keywords such as "work", "stop", "home", all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint "stay", "hand", "mask". it can be inferred that these tweets were talking about staying home, washing hands, and wearing masks. the second prevalent topic in new york was about the impact that pandemic brought, including keywords such as "business", "travel", "worker". since new york had far more confirmed cases and deaths, the negative impacts were more severe, and people might discuss more about the harm to businesses and traveling restrictions. in contrast, tweets from california talked less about working impacts according to the topic modeling keywords, presumably due to less serious situations. topics related to government and policy seem to be the next mostly discussed categories. keywords including "trump", "president", and "crisis" appeared in tweets from both states with high frequencies. other than the prevention and impacts of covid- , people paid significant attention to the government policy and president's actions, which might partially explain the fluctuation of sentiment scores. hospital environment and medical support were other popular topics in both states. although social media provides first-hand users' perspectives, it does not provide controlled variables. we don't have the user demographic information, including age, gender, and education, etc. twitter users can't represent the whole population, since about only % of us adults are currently using twitter. furthermore, our study only focused on the beginning of covid- epidemic in the us, and the story might evolve later. this study used social media data from twitter to analyze the sentiment scores and public opinions towards the emergence of covid- in california and new york states in the united states at the beginning of the covid- epidemic. this study showed how covid- affected people's attitudes from different states in a timely manner. the results from this study could provide guidelines for future social media research on the associations between the outbreak of covid- and public opinions, as well as valuable suggestions on future pandemic research. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint coronavirus (covid- ) frequently asked questions coronavirus disease (covid- ) -events as they happen detecting themes of public concern: a text mining analysis of the centers for disease control and prevention's ebola live twitter chat dataset on dynamics of coronavirus on twitter list of cities and towns in california global covid- tracker & interactive charts: real time updates & digestable information for everyone vader: a parsimonious rule-based model for sentiment analysis of social media text topic modeling and latent dirichlet allocation (lda) in python ldavis: a method for visualizing and interpreting topics california coronavirus map and case count coronavirus death toll in new york surpasses , , less than weeks after st reported death coronavirus timeline: tracking major moments of covid- pandemic in san francisco bay area all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted the project described in this publication was supported by the university of rochester clinical and translational science award ul tr from the national center for advancing translational sciences of the national institutes of health (dl). key: cord- - xrdv m authors: nowland, megan h.; brammer, david w.; garcia, alexis; rush, howard g. title: biology and diseases of rabbits date: - - journal: laboratory animal medicine doi: . /b - - - - . - sha: doc_id: cord_uid: xrdv m beginning in , an inbred rabbit colony was developed at the phipps institute for the study, treatment and prevention of tuberculosis at the university of pennsylvania. this colony was used to study natural resistance to infection with tuberculosis (robertson et al., ). other inbred colonies or well-defined breeding colonies were also developed at the university of illinois college of medicine center for genetics, the laboratories of the international health division of the rockefeller foundation, the university of utrecht in the netherlands, and jackson laboratories. these colonies were moved or closed in the years to follow. since , the u.s. department of agriculture has reported the total number of certain species of animals used by registered research facilities ( ). in , , rabbits were used in research. there has been an overall decrease in numbers of rabbits used. this decreasing trend started in the mid- s. in , , rabbits were used in research. despite the overall drop in the number used in research, the rabbit is still a valuable model and tool for many disciplines. the rabbit has been utilized in immunology research for many years especially in regard to the structure of immunoglobulins and the genetic control of their formation. in addition, the rabbit is commonly used for the production of polyclonal antibodies for use as immunologic reagents (mage, ; pinheiro et al., ) . the relatively large body size and blood volume, easy access to the vascular system, and an existent large body of information on the purification of rabbit immunoglobulins are a few reasons the rabbit is preferred over other common laboratory animal species for polyclonal antibody production (stills, ) . the organization of the lymphoid system of the rabbit is comparable to that of other mammals. however, the rabbit does possess two gut-associated lymphoid tissues (galt) with specialized functions in the maturation of igm + b cells. these are the vermiform appendix at the distal end of the cecum and the sacculus rotundus at the ileocecal junction (mage, ) . for many years, the lack of rabbit-specific immunological reagents has limited the study of inflammation and immunity in the rabbit. the use of real-time polymerase chain reaction (rt-pcr) techniques has overcome this limitation and permitted such studies in many species other than man and mice. a quantitative real-time rt-pcr assay for measuring mrna for rabbit cytokines ifn-γ, il- , il- , il- , and tnf-α has been described (godornes et al., ) . recently, schnupf and sansonetti ( ) reported on rt-pcr primer pairs for analysis of three chemokines and ccl ) and cytokines (il- β, il- , il- , il- , il- , il- p , il p , il- a, il- f, . the profile of cytokines in the rabbit appears similar to other mammals. in mice and humans, the primary antibody repertoire is created by combinatorial rearrangement of a large number of immunoglobulin gene segments. other species (chicken, sheep, cattle, and rabbit) that have a limited number of gene segments utilize somatic gene conversion and/or somatic hypermutation (pinheiro et al., ) . in the former, a portion of the immunoglobulin gene is replaced with a gene sequence from a nonfunctional pseudogene. in the latter, single-nucleotide changes are made in the immunoglobulin genes (jenne et al., ) . in the rabbit, gene diversification occurs initially in the fetus and the neonate in sites such as the bone marrow. subsequently, between and weeks of age, immature igm + b cells undergo further diversification in the galt (appendix, sacculus rotundus, and peyer's patches) (mage et al., ; pinheiro et al., ) . furthermore, certain species of intestinal bacteria (bacteroides fragilis and bacillus subtilis) are required for appendix follicle development and antibody diversification to occur (hanson and lanning, ; mage et al., ) . most mammals express five classes of immunoglobulins: igm, igd, igg, iga, and ige. however, the rabbit lacks igd (sun et al., ) . the area of cardiovascular research has used the rabbit in a variety of different models. numerous dietary modifications will induce or exacerbate cholesterolinduced atherosclerosis in the rabbit. a brief overview of some of these dietary modifications can be found elsewhere (jayo et al., ) . research efforts into cholesterol metabolism have used the watanabe heritable hyperlipidemic (whhl) (atkinson et al., ; kita et al., ) and the st. thomas hospital strain rabbits (laville et al., ) . the whhl rabbit has a marked deficiency of low-density lipoprotein (ldl) receptors in the liver and other tissues. selective breeding of the whhl rabbit will increase the incidence of coronary artery atherosclerosis without increasing the incidence of aortic atherosclerosis (watanabe et al., ) . in contrast, the st. thomas hospital strain has a normal functioning ldl receptor but still maintains a hypercholesterolemic state (laville et al., ) . genetically modified rabbits have been created via both intracytoplasmic injection (li et al., ) and retroviral vectors (hiripi et al., ) . this has resulted in a multitude of new strains to address interesting research questions. cardiovascular disease (lombardi et al., ; peng, ; sanbe et al., ; stanley et al., ) including models of long qt interval for exploration of treatments (biermann et al., ; jindal et al., ; liu et al., a; peng, ; sanbe et al., ; ziv et al., ) and atherosclerosis (araki et al., ; masson et al., ; tjwa et al., ) are the main focus of model development. strains have also been developed that express human recombinant proteins in rabbit milk (chrenek et al., ; dragin et al., ; hiripi et al., ; houser et al., ; lipinski et al., ; simon et al., ; soler et al., ) . this ability can be passed down for multiple generations (chrenek et al., ; dragin et al., ) . these human proteins have resulted in antigen production for rotavirus vaccine creation, human factor viii that could be used to treat hemophilia (chrenek et al., ; krylov et al., ; simon et al., ) and human growth hormone that could supplement a deficiency in that hormone (lipinski et al., ) . rabbits that express enhanced green fluorescent protein (egfp) in various tissues have been created for the purpose tracking cells, which is important for tissue engineering and regenerative medicine studies takahashi et al., ; yin et al., ) . the mouth of the rabbit is relatively small, and the oral cavity and pharynx are long and narrow. the dental formula is i / , c / , pm / , m - / × = or teeth. a small pair of incisors is present directly caudal to the primary maxillary incisors and is referred to as 'peg' teeth. the peg teeth are used along with the primary incisors to bite and shear food. the absence of second incisors has been noted in some rabbit colonies as a dominant trait (i /i or i /i ). the teeth of rabbits erupt continuously throughout life and therefore will continue to grow unless normal occlusion and use are sufficient to wear teeth to a normal length. molars do not have roots and are characterized by deep enamel folds. rabbits normally masticate with a chewing motion that facilitates grinding of food by movement of the premolars and molars from side to side and front to back. the rabbit has four pairs of salivary glands, including the parotid, submaxillary, sublingual, and zygomatic. the parotid is the largest and lies laterally just below the base of the ear. the zygomatic salivary gland does not have a counterpart in humans. the esophagus of the rabbit has three layers of striated muscle that extend the length of the esophagus down to, and including, the cardia of the stomach. this is in contrast to humans and many other species, which have separate portions of striated and smooth muscle along the length of the esophagus. there are no mucous glands in the esophagus of the rabbit. although the stomach of the rabbit holds approximately % of the volume of the gastrointestinal tract, it is never entirely empty in the healthy rabbit. the gastric contents often include a large amount of hair ingested as the result of normal grooming activity. the stomach is divided into the cardia, fundus, and pylorus. the liver has four lobes. the gallbladder is located on the right. from the liver, the common bile duct empties into the duodenum posterior to the pylorus. rabbits produce relatively large amounts of bile compared to other common species. the pancreas is diffuse within the mesentery of the small intestine and enters the duodenum - mm distal to the common bile duct. the small intestine of the rabbit is short relative to that of other species and comprises approximately % of the total length of the gastrointestinal (gi) tract. because the gi tract of the rabbit is relatively impermeable to large molecules, kits receive most of their passive immunity via the yolk sac prior to birth rather than by colostrum. peyer's patches are found along the ileum, particularly near the cecal junction. the sacculus rotundus is a large bulb of lymphoid tissue located at this junction. the large intestine includes the cecum, the ascending colon, the transverse colon, and the descending colon. the ileocecal valve regulates flow of chyme into the cecum and retards reverse flow back into the ileum. the cecum is very large with a capacity approximately -times that of the stomach. the cecum ends in a blind sac, the appendix. the colon is divided into proximal and distal portions by the fusus coli, which serves to regulate the elimination of hard versus soft fecal pellets. hard pellets comprise about two-thirds of the fecal output. soft pellets, or 'cecotrophs,' have a high moisture content and are rich in nitrogen-containing compounds (ferrando et al., ) and the Β vitamins niacin, riboflavin, pantothenate, and cyanocobalamin. rabbits consume cecotrophs directly from the anus to obtain significant nutritional benefit. soft pellets are sometimes termed 'night feces,' since they are generally produced at night in domestic rabbits. in contrast, the circadian rhythm of cecotrophy is reversed in wild rabbits, occurring during the day when the animals are in their burrows (hornicke, ) . nostrils of rabbits are well equipped with touch cells, and they have a well-developed sense of smell. nasal breathing in rabbits is characterized by twitching of the nostrils at rates varying from to times per minute, although twitching may be absent in the relaxed rabbit. it has been speculated that inspiration occurs as the nostril moves up and that this serves to direct the flow of air over the turbinate bones where the olfactory cells are most concentrated. the musculature of the thoracic wall contributes little to respiratory efforts. instead, rabbits rely mostly on the activity of the diaphragm. because of this, artificial respiration is easily performed by alternating the head of the rabbit between the up and down positions, - times per minute, while holding the animal. compression and release of the chest wall is an ineffective means of artificial respiration in the rabbit. the pharynx of the rabbit is long and narrow, and the tongue is relatively large. these features make endotracheal intubation difficult. the procedure is further laboratory animal medicine complicated by the propensity of the rabbit to laryngospasm during attempts to intubate the trachea. the rabbit lungs consist of six lobes. both right and left sides have cranial, middle, and caudal lobes, with the right caudal being further subdivided into lateral and medial portions. flow volume of air to the left lung is higher than that to the right due to the lower resistance of the proximal airways per unit volume (yokoyama, ) . in rabbits, lung volume increases with age, in contrast to that of humans and dogs, in which it decreases. bronchial-associated lymphoid tissue (balt) is present as distinct tissue. a unique feature of the cardiovascular system of the rabbit is that the tricuspid valve of the heart has only two cusps, rather than three as in many other mammals. a small group of pacemaker cells generate the impulse of the sinoatrial (sa) node in the rabbit, a feature that facilitates precise determination of the location of the pacemaker (bleeker et al., ; hoffman, ; west, ) . the sa and atrioventricular (av) nodes are slender and elongated, and the av node is separated from the annulus fibrosus by a layer of fat (truex and smythe, ) . additional unique anatomic features of the cardiovascular system of the rabbit have been utilized to advantage. the aortic nerve subserves no known chemoreceptors (kardon et al., ; stinnett and sepe, ) and responds to baroreceptors only. because the aortic nerve, which becomes the depressor nerve, runs alongside but separate from the vagosympathetic trunk, it lends itself readily to implantation of electrodes (karemaker et al., ) . the blood supply to the brain is restricted mainly to the internal carotid artery. blood supplied via the vertebral arteries is limited. the aorta of the rabbit demonstrates rhythmic contractions that arise from neurogenic stimulation in a pattern related to the pulse wave (mangel et al., ) . the kidneys of the rabbit are unipapillate in contrast to those of most other mammals, which are multipapillate. this feature increases the ease with which cannulization is performed. the right kidney lies more cranial than the left. glomeruli increase in number after birth in rabbits, whereas all of the glomeruli are present at birth in humans (smith, ) . ectopic glomeruli are normal in the rabbit (steinhausen et al., ) . blood vessels that perfuse the medulla remain open during many conditions under which vasoconstriction of the cortical tissue occurs; thus, the medullary tissue may be perfused, while the cortex is ischemic (trueta et al., ) . the urine of adult rabbits is typically cloudy due to a relatively high concentration of ammonium magnesium phosphate and calcium carbonate monohydrate precipitates (flatt and carpenter, ) . the urine may also take on hues ranging from yellow or reddish to brown. in contrast, the urine of young rabbits is typically clear, although healthy young rabbits may have albuminuria. the urine is normally yellow but can also take on reddish or brown hues once animals begin to eat green feed and cereal grains. normal rabbits have few cells, bacteria, or casts in their urine. the ph of the urine is typically alkaline at about . (williams, ) . a normal adult rabbit produces approximately - ml/kg of urine daily (gillett, ) , with does urinating more copiously than bucks. the urethral orifice of the buck is rounded, whereas that of the doe is slit-like. this feature is useful for distinguishing the sexes. the testes of the adult male usually lie within the scrotum; however, the inguinal canals that connect the abdominal cavity to the inguinal pouches do not close in the rabbit. for this reason, the testes can easily pass between the scrotum and the abdominal cavity. this feature necessitates closure of the superficial inguinal ring following orchiectomy by open technique to prevent herniation. the reproductive tract of the doe is characterized by two uterine horns that are connected to the vagina by separate cervices (bicornuate uterus). a common tube, the urogenital sinus or vestibulum, is present where the urethra enters the vagina. the placenta is hemochorial, and maternal blood flows into sinus-like spaces where the transfer of nutrients and other substances to the fetal circulation occurs (jones and hunt, ) . inguinal pouches are located lateral to the genitalia in both sexes. the pouches are blind and contain scent glands that produce white to brown secretions that may accumulate in the pouch. the metabolic rate of endotherms is generally related to the body surface area. including the ears, the rabbit has a relatively low metabolic rate (mr); however, if the surface area of the ears is discounted, the mr of the rabbit is similar to that of other endotherms. neonatal rabbits have an amount of body fat comparable to that of the human infant ( % of body weight) (cornblath and schwartz, ) . the neonatal rabbit is essentially an ectotherm until about day (gelineo, ) . the glucose reserves of the neonatal rabbit are quickly depleted, usually within about h after birth (shelley, ) . the fasting neonatal rabbit quickly becomes hypoglycemic and ketotic (callikan and girard, ) . the normal rectal temperature of the adult new zealand white rabbit at rest is approximately . - . °c (ruckebusch et al., ) . the ears serve an important thermoregulatory function. because they have a large surface area and are highly vascular with an extensive arteriovenous anastomotic system, the ears help the rabbit sense laboratory animal medicine and respond to cold versus warm temperatures (kluger et al., ) . in addition, the ears serve as a countercurrent heat-exchange system to help adjust body temperature. early studies found that the body of the adult rabbit ( kg body weight) consists of greater than % water ( %), with a half-time turnover of about . days and a loss of about ml daily (richmond et al., ) . the amount of water ingested varies with the amount and type of feed consumed and the environmental temperature. in general, rabbits will drink more water when consuming dry, pelleted feed than when consuming foodstuffs high in moisture, such as fresh greens. conversely, rabbits deprived of water will decrease food consumption. after days of complete water deprivation, food intake falls to less than % of normal (cizek, ) . normal values for various systems and parameters are provided as a general indication for these values in the rabbit. it is important to recognize, however, that most of these values have been obtained through the study of adult new zealand white rabbits. as with any experiment, values can vary significantly between breeds, laboratories, methods of sampling and measurement, and individual rabbits due to age, sex, breed, health, handling, and husbandry (hewitt et al., ; lidena and trautschold, ; mitruka and rawnsley, ; wolford et al., ; yu et al., ) . for this reason, individual laboratories should strive to establish their own normal values, whenever possible. values for hematologic parameters are shown in table . . these values represent those typical of adult new zealand white rabbits. in general, males have slightly greater hematocrit and hemoglobin values than females (mitruka and rawnsley, ) . anisocytosis is normal and accounts for variation in reported values for red blood cell diameter (sanderson and phillips, ) . reticulocyte values are usually between % and % in healthy rabbits (corash et al., ) . the neutrophil of the rabbit is sometimes referred to as a 'pseudoeosinophil' or 'heterophil,' due to the presence of red-staining granules in the cytoplasm. the heterophil ( - mm in diameter) is, however, smaller than the eosinophil ( - mm in diameter) (sanderson and phillips, ) . in addition, the red granules of the heterophil are smaller than the red granules of the eosinophil. the nucleus of the eosinophil may be either bilobed or horseshoe-shaped. as mentioned earlier, chemistry values can vary because of a number of factors. for this reason, each laboratory should establish its own normal values. aspartate aminotransferase (ast) is present in the liver, heart, skeletal muscle, kidney, and pancreas. collection of blood samples in rabbits by decapitation, cardiac puncture, or aortic incision, or the use of restraint that causes exertion will elevate ast levels due to muscle damage (lidena and trautschold, ) . similarly, levels of creatinine kinase are sensitive to muscle damage since that enzyme is present in the skeletal muscle, brain, and heart (lidena and trautschold, ; mitruka and rawnsley, ) . although most mammals have two isoenzymes (intestinal and a liver/kidney/bone form) of alkaline phosphatase (ap), rabbits are unique in having three forms of ap, including an intestinal form and two forms that are both present in the liver and the kidney (noguchi and yamashita, ) . values for blood and serum chemistry are shown in table . . cardiovascular and respiratory functions are often altered with experimental manipulation, anesthesia, or disease. normal values for these parameters and other miscellaneous biologic characteristics of the rabbit are listed in table . . values obtained from the following sources: burns and delannoy ( ) , gillett ( ) , kabata et al. ( ) , mitruka and rawnsley ( ), and woolford et al. ( ) . laboratory animal medicine rabbits are strictly herbivorous with a preferred diet of herbage that is low in fiber and high in protein and soluble carbohydrate (cheeke, ; cheeke, ) . rabbits will generally accept a pelleted feed more readily than one in meal form. when a meal diet is needed, a period of adjustment should be allowed for the rabbits to accommodate to the new diet. examples of adequate diets are shown in table . . the requirement for fiber in the diet of rabbits has been reviewed (gidenne, ) . fiber is especially important in the early postweaning period when low fiber intake is associated with an increase in digestive disorders (gidenne, ) . the exact nutrient requirements for individual rabbits vary with age, reproductive status, and health of the animal. on occasion, the need arises for use of highly purified diets. a suggested purified diet has been described elsewhere (subcommittee on rabbit nutrition, ) . it should be noted that overfeeding of values obtained from the following sources: burns and delannoy ( ) , fox ( ) , gillett ( ) , kraus et al. ( ), and loeb and quimby ( ) . values obtained from the following sources: barzago et al. ( ) , curiel et al. ( ) , gillett ( ) , kozma et al. ( ) , sanford and colby ( ) , suckow and douglas ( ), and zurovsky et al. ( ) . laboratory animal medicine laboratory rabbits resulting in obesity is common, but can be prevented by either reducing the amount of feed or by providing a low-energy, high-fiber maintenance diet (donnelly, ) . as mentioned earlier, rabbits engage in cecotrophy, and by doing so supplement their supply of protein and Β vitamins (carabaño et al., ; gidenne et al., ) . rabbits fed a diet high in fiber ingest a greater quantity of cecotropes than those on a lower fiber diet (fekete and bokori, ) . unlike most other species, both calcium absorption in the small intestine and serum calcium levels increase in proportion to the amount of calcium in the diet (cheeke, ) . prolonged feeding of diets high in calcium, such as those with a high level of alfalfa meal, can result in renal disease. consumption of diets containing excessive vitamin d can result in calcification of soft tissues, including the liver, kidney, vasculature, and muscles (besch-williford et al., ; lebas, ) . diets that are either too high or too low in vitamin a can result in reproductive dysfunction and congenital hydrocephalus (cheeke, ; digiacomo et al., ) . the exact requirement for vitamin a in the rabbit has not been determined; however, a level of - , iu/kg of diet is generally adequate (lebas, ) . vitamin e deficiency has been associated with infertility, muscular dystrophy, fetal death, neonatal death, and colobomatous microphthalmos in rabbits (lebas, ; nielsen and carlton, ; ringler and abrams, ; ringler and abrams, ) . mcdowell ( ) suggested that serum vitamin e levels of less than . μg/ml are indicative of hypovitaminosis e. relative to other species, rabbits have a high water intake. in general, daily water intake is approximately ml/kg of body weight. consumption of water is influenced by environmental temperature, disease states, and feed composition and intake (cizek, ; tschudin et al., ) . consumption of diets high in dry matter results in increased water intake (tschudin et al., ) . water consumption also increases with food deprivation. rabbits are social animals and attempts at group housing often meet with success, although mature males will fight and can inflict serious injury on one another (love, ; podberscek et al., ; whary et al., ) . group-penned female rabbits allowed to choose between single or paired housing prefer being in the same cage with other rabbits (huls et al., ) . in general, rabbits are timid and nonaggressive. some animals will display defensive behavior, typically characterized by thumping the cage floor with the rear feet, biting, and charging toward the front of the cage when opened. laboratory-housed rabbits demonstrate diurnal behavior, in contrast to the nocturnal pattern exhibited by wild rabbits (jilge, ) . the ethogram of the laboratory rabbit has been described (chu et al., ; gunn and morton, ) . the most common behaviors of individually housed rabbits included lie alert, doze, groom, sleep, and eat. individually housed rabbits were inactive the majority of the time (gunn and morton, ) . individually housed female rabbits showed an increase in abnormal behaviors compared to pair-housed rabbits (chu et al., ) . rabbits housed in pairs in double-wide cages locomoted more than individually housed rabbits (chu et al., ). the age of puberty varies with the breed of rabbit. puberty generally occurs at - months of age in small breeds, - months in medium breeds, and - months in large breeds (donnelly, ) . female new zealand white rabbits reach maturity at months of age and males at - months. the breeding life of a doe typically lasts approximately - years, although some remain productive for up to or years. in later years, litter sizes usually diminish. in comparison, most bucks will remain reproductively useful for an average of - years. because does often will engage in reproductive behavior before being able to ovulate, it is advisable not to breed does until they are fully grown. does do not have a distinct estrous cycle, but rather demonstrate a rhythm with respect to receptivity to the buck. receptivity is punctuated by periods ( - days every - days) of anestrus and seasonal variations in reproductive performance (hafez, ) . during periods of receptivity, the vulva of the doe usually becomes swollen, moist, and dark pink or red. receptivity of the doe is usually signaled by lordosis in response to the buck's attempt to mount, vulvar changes as described above, restlessness, and rubbing of the chin on the hutch or cage (donnelly, ) . vaginal cytology is generally not useful for determination of estrus or receptivity in the rabbit. typically, the doe is brought to the buck's cage for breeding, since the doe can be very territorial and may attack the male in her own quarters. a period of - min is usually sufficient to determine compatibility of the doe and buck. if receptive, the doe will lie in the mating position and raise her hindquarters to allow copulation. if fighting or lack of breeding is observed, the doe may be tried with another buck. a single buck is usually sufficient to service - does. ovulation is induced and occurs approximately - h after copulation (donnelly, ) . up to % of does fail to ovulate following copulation. ovulation can also be induced by administration of luteinizing hormone (kennelly and foote, ) , human chorionic gonadotropin (williams et al., ) , or gonadotropic releasing hormone (foote and simkin, ) . does may be bred immediately after kindling; however, most breeders delay until after the kits have been weaned. success at postpartum breeding varies, but one can produce a large number of kits in a relatively short time period by foster nursing the young and rebreeding the doe immediately. while conventional breeding, nursing, and weaning schedules allow for only litters per year, early postpartum breeding allows for up to litters per year. pregnancy can often be confirmed as early as day of gestation by palpation of the fetuses within the uterus. radiographic procedures permit pregnancy determination as early as day . conception rates have been observed to have an inverse relationship with ambient temperature but not light cycle. gestation in rabbits usually lasts for - days (donnelly, ) . does beyond - weeks of gestation will usually refuse a buck. does begin hair pulling and nest building during the last - days of gestation (donnelly, ) . a nesting box with shredded paper or other soft material such as straw should be provided to the doe several days prior to the expected kindling (parturition) date. the doe will usually line the box with her own hair. the nesting box should not be placed in the corner of the cage where the individual doe has been observed to urinate. pseudopregnancy is common in rabbits and can follow a variety of stimuli, including mounting by other does, sterile matings by bucks, administration of luteinizing hormone, or the presence of bucks nearby. in such circumstances, ovulation is followed by a persistent corpus luteum that lasts - days. the corpus luteum or corpora lutea secretes progesterone during this time, causing the uterus and mammae to enlarge. the doe may have the appearance of a normally pregnant rabbit. toward the end of pseudopregnancy, many does will begin to pull hair as part of ritual nest-building behavior. the process of parturition is referred to as 'kindling' when it relates to rabbits. kindling normally occurs during the early morning hours and takes approximately - min. impending kindling is often signaled by nest building and decreased food consumption during the preceding - days. both anterior and breech presentations are normal in the rabbit. fetuses retained beyond days generally die and may harm future reproductive ability of the doe if not expelled. the average number of kits born is seven to nine per litter, although smaller litters and litters of up to kits are not uncommon. breed, parity, nutritional status, and environmental factors influence litter size. polish rabbits usually have fewer than four kits per litter; dutch or flemish giant, four to five; and new zealand white, eight to ten. after the young have been cleaned following parturition, the doe typically consumes the placenta. cannibalism of the young by the doe sometimes occurs and may be related to environmental or hereditary factors or due to environmental stressors. does usually have either four or five pairs of nipples, whereas bucks have none. during the last week of pregnancy, marked development of the mammary gland occurs. the doe normally nurses the kits once daily for several minutes, usually in the early morning or in the evening, regardless of how many kits are present or laboratory animal medicine how many times they attempt to suckle. milk yield is normally between and g/day. during the first week of life, kits consume - g of milk per day. milk intake increases gradually to a maximum of g/day between and days of age (gidenne et al., ) . maximum output occurs at weeks following kindling and then declines during the fourth week. rabbit milk contains approximately . % protein, % fat, % lactose, and . % minerals. nursing may last - weeks. kits may begin consuming solid food by weeks of age, with weaning generally occurring by - weeks of age. the facilities present in most modern research animal facilities would be suitable for housing rabbits. general construction should include adequate heating, ventilation, and air conditioning to house rabbits at appropriate temperature and humidity. in addition, lighting should be adequate to allow easy visualization of the rabbits. surfaces, such as the floors, walls, and ceilings, should be easily sanitizable (national research council, ) . rabbit cages should provide a safe environment with easy access to food and water. adults can be caged individually or in compatible groups and should have sufficient floor space to lie down and stretch out. in the united states, minimum cage sizes are determined by the animal welfare act (awa) and the guide for the care and use of laboratory animals (guide). in both cases, sizes vary with the weight of the animal. currently, the awa regulations and the guide require . ft of floor space and in of cage height for rabbits weighing - kg (national research council, ) . cages should be constructed of durable materials that will resist corrosion and harsh detergents and disinfectants used in cleaning. consequently, in the research environment, rabbit cages are most often constructed of stainless steel or plastics. rabbits are usually housed in cages with mesh or slatted floors to permit urine and feces to drop through into a catch pan. mesh floors with catch pans do not prevent rabbits from engaging in the normal practice of coprophagy. information on environmental enrichment of laboratory rabbits has been published (baumans, ) . the behavior of rabbits in conventional cages was compared to that of rabbits provided with enriched cages that contained shelter, a shelf, and increased vertical space. rabbits in conventional cages were more restless, groomed excessively, exhibited more bar-gnawing, and were more timid than those housed in enriched cages (hansen and berthelsen, ) . indeed, fecal glucocorticoid levels in rabbits declined when they were provided with a wooden structure for resting and gnawing (buijs et al., ) . rabbits will play with objects placed in their cages. huls et al. ( ) noted that rabbits would use wooden sticks, wooden rings, and brass wire balls as toys. rabbits provided with objects (toys) spent significantly more time chewing than rabbits without toys (poggiagliolmi et al., ) . female rabbits can also be housed in compatible pairs or groups. singly housed female rabbits exhibited more abnormal behaviors compared to pair housed rabbits (chu et al., ) . group housing of unfamiliar males is not recommended because of the likelihood of fighting and injury. rabbits are optimally housed in cooler room temperatures than most other common species of laboratory animals. the guide recommends that temperatures in rabbit rooms be maintained between and °f. no specific illumination requirements for rabbits have been described. it is common practice to provide rabbits with - h of light in the light-dark cycle. in breeding colonies, females should be provided with - h of light. rabbits are easily startled by sudden, loud noises. for this reason, they should not be housed near noisy species such as dogs or monkeys, nor should they be housed near noise-generating operations such as the cage-wash area. catch pans should be cleaned as often as necessary to prevent the formation of ammonia. cages are generally sanitized on at least a weekly basis. rabbit urine contains large amounts of protein and minerals, and often forms deposits on cages and catch pans. it is common practice to soak equipment having urine deposits in acid washes to remove the scale before washing. ammonia production in rabbit rooms can be a significant problem; therefore, rabbit rooms should be ventilated at - air changes per hour (national research council, ) . it is also important to change excreta pans often to prevent the buildup of ammonia. etiology pasteurella multocida is a gram-negative nonmotile coccobacillus that causes pasteurellosis, also known as 'snuffles', the primary respiratory disease affecting domestic rabbits (deeb and digiacomo, ; guo et al., ) . historically, serogroup a isolates have laboratory animal medicine been associated with pneumonic and septicemic pasteurellosis in laboratory rabbits; however, capsular type a is also isolated from rabbits that appear clinically healthy (confer et al., ; el tayeb et al., ) . clinical signs pasteurella multocida infection is often subclinical, but pasteurellosis may cause fever, coughing, dyspnea, rhinitis (nasal discharge (serous to mucopurulent), sneezing, and upper airway stentor), pneumonia, otitis, septicemia, meningitis, abscesses (of viscera and subcutaneous sites), and death (al-lebban et al., ; confer et al., ; franco and cronin, ; guo et al., ; suckow et al., ; wilkie et al., ) . pasteurellosis may also be associated with pericarditis, pleuritis, sinusitis, dacryocystitis, conjunctivitis, iritis/ uveitis, phlegmon, mastitis, endometritis, pyometra, salpingitis, and orchitis (deeb and digiacomo, ; ferreira et al., ; stahel et al., ; williams, ) . epizootiology p. multocida can be endemic in rabbitries and is carried in the rabbit's nasal cavity (confer et al., ; deeb et al., ; digiacomo et al., ; suckow et al., ) . transmission is by direct contact between rabbits (wilkie et al., ) . coinfection with bordetella bronchiseptica may be observed in clinically affected rabbits (deeb et al., ) . stress-related factors associated with pasteurellosis include crowded or unsanitary conditions, transportation, and high ammonia concentrations in the air (confer et al., ) . previous studies reported a high prevalence of p. multocida infection (jaslow et al., ) . colonization in immature rabbits occurs more commonly in the sinuses followed by the trachea, middle ears, and lungs (glass and beasley, ) . similar to cats and dogs, rabbits may transmit p. multocida infection to humans (per et al., ; silberfein et al., ) . a study utilizing repetitive extragenic palindromic pcr (rep-pcr) and sequencing determined that % of the isolates were characterized as p. multocida subsp. multocida, % as p. multocida subsp. septica, % as atypical subspecies of p. multocida, % as p. canis, and % as an unknown species of the family pasteurellaceae (stahel et al., ) . the pathogenesis of p. multocida has been reviewed (wilkie et al., ) . the ptfa gene, encoding a type fimbrial subunit and involved in bacterial fixation on the surface of epithelial cells, may be highly prevalent in p. multocida isolates from rabbits (ferreira et al., ) . the p. multocida toxin is a major virulence factor in atrophic rhinitis of rabbits and acts by causing constitutive activation of g proteins frymus et al., ; orth et al., ; suckow et al., ) . pathology the specific pathologic findings will vary with the site of infection, but the underlying host response is characterized by acute or chronic suppurative inflammation with the infiltration of large numbers of neutrophils. rhinitis and sinusitis are accompanied by a mucopurulent nasal exudate. neutrophil infiltration of the tissues is extensive. the nasal passages are edematous, inflamed, and congested, and there may be mucosal ulcerations. the turbinate bones may atrophy digiacomo et al., ) . purulent conjunctivitis may be present. pneumonia is primarily cranioventral in distribution. the lungs can exhibit consolidation, atelectasis, and abscess formation. a purulent to fibrinopurulent exudate is evident, and there may be areas of hemorrhage and necrosis. in some rabbits, fibrinopurulent pleuritis and pericarditis are prominent features (glavits and magyar, ) . this is probably due to elaboration of a heat-labile toxin in some strains of the bacteria . acute hepatic necrosis and splenic lymphoid atrophy are also seen in association with the pleuritis and pneumonia induced by toxigenic strains. otitis media is characterized by a suppurative exudate with goblet cell proliferation and lymphocytic and plasma cell infiltration. in female rabbits with genital tract infections, the uterus may be enlarged and dilated. in the early stages of infection, the exudate is watery; later it thickens and is cream-colored. the exudate contains numerous neutrophils. focal endometrial ulceration can be found (johnson and wolf, ) . in the male, the testes are enlarged and may contain abscesses. systemic and visceral abscesses are characterized by a necrotic center, an infiltrate made up of polymorphonuclear neutrophils, and a fibrous capsule. septicemia may only present as congestion and petechial hemorrhages in many organs. severe pleuritis with accumulation of fibrinopurulent exudate in the thoracic cavity, serous rhinitis and tracheitis, acute hepatitis with necrotic foci in the parenchyma, and atrophy of lymphoid organs and tissues have been observed after experimental p. multocida infection in rabbits (glavits and magyar, ) . diagnosis sterile swabs can be used to collect samples from the nares or nasal cavity of rabbits for culture (ferreira et al., ; jaslow et al., ) . nasal lavage can also be used as a culture sample to isolate pasteurella (suckow et al., ) . p. multocida isolates can be classified into five serogroups based on capsular antigens (a, b, d, e, and f) and into serotypes based on somatic lps antigens (adler et al., ; liu et al., b; manning, ) . biochemical characterization of isolates may show high heterogeneity; however, rep-pcr and phylogenetic analysis using s ribosomal rna and rpob genes can be used for precise characterization of rabbit isolates (stahel et al., ) . classification of p. multocida into subspecies and/or by virulence profiles is useful for epidemiological investigations (ferreira et al., ; stahel et al., ) . random amplified polymorphic laboratory animal medicine dna pcr (rapd-pcr) has also been used to subtype rabbit p. multocida isolates (al-haddawi et al., ; dabo et al., ; williams et al., ) . pcr can detect capsule biosynthesis genes cap a, b, d, e, and f as well as virulence-related genes (ferreira et al., ) . serological tests can be used to detect antibodies against p. multocida (deeb et al., ; delong et al., ; digiacomo et al., ; glass and beasley, ; lukas et al., ) . differential diagnoses if radiographs reveal an internal mass associated with p. multocida infection, the differential diagnoses should include abscess, granuloma, neoplasia, and parasitic cyst (franco and cronin, ) . treatment, prevention, and control previous studies have investigated the use of vaccines to protect rabbits against p. multocida infection (confer et al., ) . immunization of rabbits with inactivated heat-labile p. multocida toxin or a commercial swine p. multocida bacterin-toxoid conferred protective immunity against challenge with the p. multocida heat-labile toxin (suckow, ; suckow et al., ) . a vaccine administered intranasally stimulated immunity against experimental pneumonic pasteurellosis and significantly reduced nasal bacterial counts (confer et al., ) . oral immunization of rabbits with a p. multocida thiocyanate extract (pte) in microparticles was immunogenic and significantly reduced the colony-forming units of homologous p. multocida recovered from the lungs and nasopharynx (suckow et al., ) . protective immunity to a heterologous strain of p. multocida can be achieved by vaccinating rabbits with pte via the subcutaneous route (suckow et al., ) . a p. multocida bacterin known as bunnyvac is currently licensed by the usda and is intended to be effective in preventing death and limiting disease due to pasteurella in rabbits. bunnyvac is manufactured by colorado serum company and distributed by pan american veterinary laboratories (http://pavlab. com/). control of pasteurellosis in rabbitries entails testing and culling animals that are positive for pasteurella spp. (ferreira et al., ) . furthermore, rabbits free of pasteurella and other infectious agents can be obtained by enrofloxacin treatment and through cesarean section or hysterectomy rederivation (pleasants, ; suckow et al., ; syukuda, ) . commercial suppliers of laboratory rabbits tend to exclude pasteurella from their colonies. treatment with antibiotics should be based on culture and sensitivity. antibiotic treatment of affected rabbits can alleviate clinical signs or delay disease progression but may not eradicate the disease (el tayeb et al., ; ferreira et al., ) . antibiotic treatment may suppress virulence gene expression without complete elimination of p. multocida . internal abscesses may not be treatable using antibiotics (franco and cronin, ) . penicillin therapy does not seem to be effective against pasteurella infection and may also lead to diarrhea and clostridium difficile colitis in rabbits (jaslow et al., ; rehg and lu, ) . one study from brazil determined that all tested strains were sensitive to ceftiofur, florfenicol, norfloxacin, enrofloxacin, ciprofloxacin, tetracycline, and doxycycline (ferreira et al., ) . other studies also indicate that fluoroquinolones are useful for the treatment of p. multocida infection in rabbits (abo-el-sooud and goudah, ; broome and brooks, ; franco and cronin, ; hanan et al., ; okewole and olubunmi, ) . oral ciprofloxacin ( mg/kg per day for days) has been used in rabbits (hanan et al., ) . research complications pasteurellosis can cause considerable economic losses (el tayeb et al., ; ferreira et al., ; stahel et al., ) and has the potential to affect different types of research studies using rabbits due to the multisystemic nature of the disease, and the possibility of high morbidity and mortality. therefore, pasteurella should be excluded from laboratory rabbit colonies. the class clostridia belongs to the phylum firmicutes (yutin and galperin, ) . recent genomic analyses suggest assigning some clostridium species that fall outside the family clostridiaceae into new genera. the genera tyzzerella, erysipelatoclostridium, and peptoclostridium have been proposed for c. piliforme, c. spiroforme, and c. difficile, respectively (yutin and galperin, ) . etiology c. piliforme is a pleomorphic, gramnegative, spore-forming, motile, obligate intracellular rod-shaped bacterium that causes tyzzer's disease and infects various animals including mice, nonhuman primates, gerbils, rats, rabbits, and others (allen et al., ; ganaway et al., ; pritt et al., ) . infection has also been reported in a human patient with human immunodeficiency virus- (smith et al., ) . phylogenetic analyses determined that microorganisms identified as c. piliforme form three clusters within a single clade and that the nearest related distinguishable species is c. colinum (feldman et al., ) . clinical signs the first reported outbreaks in laboratory rabbits described profuse watery to mucoid diarrhea usually followed by death in - h in -to -week old rabbits (allen et al., ) . rabbits in affected litters usually died within a week after the first fatality (allen et al., ) . the dams of affected litters occasionally died after a diarrheal disease that was more protracted than that of the offspring (allen et al., ) . these outbreaks lasted for - months and affected multiple rabbit rooms. c. piliforme infection may also be subclinical and transient as immunocompetent hosts may clear the infection (ganaway et al., ; pritt et al., ) . weanling rabbits with the acute form of tyzzer's disease exhibit diarrhea, listlessness, anorexia, and dehydration usually followed by death within h (cutlip et al., ) . the mortality rate in clinically affected rabbits was estimated to be - % (cutlip et al., ) . anorexia and stunting were observed in chronic cases associated with intestinal stenosis (cutlip et al., ) . acute and chronic tyzzer's disease types have been described in rabbits; however, large numbers of 'attaching' escherichia coli were recovered from the cecum of most rabbits (prescott, ) . epizootiology the vegetative cell is the active stage responsible for the disease and depends on the intracellular environment (ganaway, ) . therefore, the spore, a resistant stage, appears to be the essential element in the transmission of tyzzer's disease (ganaway, ; ganaway et al., ) . contact with soiled bedding or diseased rabbits have been used experimentally to transmit the disease to other rabbits (allen et al., ) . it is possible that subclinically infected rabbits (carriers) may introduce the organism into a colony (allen et al., ; pritt et al., ) . in mice, increased susceptibility to infection has been associated with stress (allen et al., ) . furthermore, treatment with cyclophosphamide, cortisone, and prednisolone has been used experimentally to reproduce the disease in animals, suggesting that immunosuppression plays a role in pathogenesis (allen et al., ; cutlip et al., ; pritt et al., ) . animals stressed by poor environmental conditions including overcrowding and extreme temperatures can develop the disease (cutlip et al., ; wobeser et al., ). significant modifications of the intestinal flora and an impaired immune system may play a role in pathogenesis (licois, ) . c. piliforme may be transported from the intestine to the liver through the portal circulation and to the heart through the lymphatics (allen et al., ) . some c. piliforme isolates can induce cytopathic effects on cell cultures, and in vivo, concomitant infection with other enteric pathogens such as e. coli may contribute to the severity of the disease (prescott, ; riley et al., ) . pathology lesions can be found in the distal ileum, cecum, proximal colon, liver, and heart (allen et al., ) . intestinal lesions are common, and histologically are characterized by necrosis of the mucosa and edema of the submucosa and serosa (allen et al., ) . bacilli appear as bundles of parallel rods or as criss crossed sticks in the cytoplasm of epithelial cells distributed from the surface of the mucosa to the base of the glands (allen et al., ) . the lesions in the liver are punctate areas of parenchymal necrosis that appear grossly as white spots, usually ≤ mm in diameter. large numbers of bacilli are found in the cytoplasm of cells in the zone of transition between the necrotic lesion and the healthy parenchyma (allen et al., ) . myocardial lesions appear as white streaks . - mm wide and - mm long extending from the region of the left interventricular groove laterally across the left ventricle (allen et al., ) . in the myocardium, bacilli may be noted in partially degenerated and normal looking cells at the sharply delineated borders of the lesions (allen et al., ) . diagnosis c. piliforme cannot be cultured in artificial (cell-free) media making its diagnosis difficult (allen et al., ; cutlip et al., ; ganaway et al., ; niepceron and licois, ) . other bacteria, including e. coli, have been isolated from the liver of diseased rabbits and are considered secondary invaders (allen et al., ; cutlip et al., ) . the isolation of the tyzzer's agent using liver extract agar has been described (kanazawa and imai, ) . c. piliforme can be grown in primary monolayer cultures of adult mouse hepatocytes, in mouse fibroblasts, in rat hepatocytes, and in embryonated eggs (craigie, ; duncan et al., ; ganaway et al., ; kawamura et al., ; pritt et al., ; riley et al., ) . serology for c. piliforme is commonly used for surveillance of laboratory animals because it is rapid and inexpensive (pritt et al., ) . immunofluorescence assay (ifa) and multiplexed fluorometric immunoassay (mfia) have been utilized (pritt et al., ) . in addition, c. piliforme pcr assays have been developed (feldman et al., ; gao et al., ; niepceron and licois, ; pritt et al., ) . clostridium piliforme seropositive rabbits may be negative for the organism by pcr and histopathological evaluation (pritt et al., ) . therefore, positive serological findings are not sufficient for a definitive diagnosis of c. piliforme infection and pcr testing and/or histopathology should be used for confirmation (pritt et al., ) . definitive diagnosis is based on identification of typical gross lesions and histological demonstration of intracellular c. piliforme at the periphery of the necrotic foci (niepceron and licois, ; pritt et al., ) . giemsa solution (ph ), warthin-starry silver method, levaditi silver method, and the periodic acid-schiff (pas) reaction have been used to demonstrate c. piliforme (allen et al., ; cutlip et al., ) . different morphologic forms of c. piliforme can be observed microscopically (allen et al., ; ganaway et al., ) . differential diagnoses clinically, other diarrheal diseases of rabbits can be included in the differential diagnoses. grossly, the multifocal white areas on the liver could be from eimeria stiedae infection (hepatic coccidiosis). treatment, prevention, and control for prevention, avoid introduction of rabbits of unknown c. piliforme status into a colony. minimize stress-related factors especially in young animals. good husbandry practices including regular bedding changes and disinfection laboratory animal medicine should decrease the likelihood of spreading c. piliforme in a colony. in one report, a tyzzer's disease outbreak was observed - days after rabbits were weaned and transferred to a facility in which the temperature fluctuated from to °c. the outbreak was controlled by transferring weanling rabbits to a building maintained at the same temperature as the breeder house ( - °c) (cutlip et al., ) . spores treated with heat ( or °c) or with either peracetic acid ( %) in a wetting agent (sodium alkylarylsulfonate) or sodium hypochlorite solution ( . %) for min lose infectivity (ganaway, ) . however, spores do not lose infectivity when treated with a phenolic germicidal agent, ethanol, or quaternary ammonium compounds (containing % or % benzalkonium chloride) (ganaway, ) . sodium hypochlorite solution ( . %) has been recommended as a surface disinfectant in animal facilities for prevention and control of tyzzer's disease (ganaway, ) . the sensitivity of c. piliforme to antibiotics has been investigated (kanazawa and imai, ) . in one study, none of the antibacterials tested were completely inhibitory (ganaway et al., ) . group treatment of rabbits with tetracyclines in the drinking water and food was effective in lowering the incidence of diarrhea and death (prescott, ) . research complications the high morbidity and mortality associated with tyzzer's disease can affect the overall population of rabbits in a colony thereby decreasing the number of rabbits suitable or available for experimentation. in addition, research studies involving experimental infection with enteric pathogens in rabbits may be confounded by c. piliforme-associated intestinal pathology. enterotoxemia refers to conditions of the bowel caused by toxigenic clostridia (carman and evans, ) . diagnosis of enterotoxemia should be based on culture of a toxigenic clostridium and demonstration of the toxin from the intestinal contents of the diseased animal (carman and evans, ; songer, ) . i. clostridium spiroforme etiology c. spiroforme is a gram-positive, sporebearing, helically coiled, semicircular, anaerobic bacterium that can produce iota toxin (borriello and carmen, ; carman and borriello, ; peeters et al., ) . the disease caused by c. spiroforme is known as 'iota enterotoxemia' (keel and songer, ; peeters et al., ) . clinical signs diarrhea, fecal soiling of the perineum, and cyanosis may be observed (carman and borriello, ) . diarrhea may be peracute and may lead to 'spontaneous' death or a moribund state (carman and borriello, ) . epizootiology c. spiroforme is thought to be acquired from the environment (carman and evans, ; songer, ) . weaning is associated with spontaneous disease and administration of antibiotics can also induce the disease (borriello and carmen, ; carman and borriello, ) . a study determined that disease results from exposure of weanling rabbits to c. spiroforme and also from exposure of adult rabbits with a disrupted gut flora (due to clindamycin treatment) to c. spiroforme suggesting that this bacterium is not a normal component of the rabbit gut flora (carman and borriello, ) . c. spiroforme-mediated diarrhea may be favored by maldigestion initiated by infectious agents and/or nutritional factors (peeters et al., ) . other clostridia, e. coli (epec), viruses, and parasites, may coinfect rabbits (peeters et al., ) . the iota toxin of c. spiroforme binds the same host cell receptor as the iota toxin of c. perfringens and the binary toxin of c. difficile (papatheodorou et al., ) . poor hygiene, stress, and diet can influence pathogenesis of the disease (bain et al., ; songer, ) . pathology grossly, ceca may be enlarged with gas, may exhibit serosal hemorrhages, and have liquid contents (carman and borriello, ) . cecal contents may be stained with blood (peeters et al., ) . c. spiroforme is mainly associated with lesions in the cecum, but may also involve lesions in the proximal colon and distal ileum (keel and songer, ) . mucosal necrosis can be observed microscopically (keel and songer, ) . the mucosa of the ileum, cecum, and colon may be denuded. cellular debris, red blood cells, and fibrin may be found in the intestinal lumen. polymorphonuclear cell infiltration and edema can be found in the lamina propria and submucosa. epithelial degeneration and dilation were found in the renal tubules of some rabbits (peeters et al., ) . diagnosis gram staining of smears prepared from intestinal contents can be used to detect c. spiroforme (bain et al., ) . clostridial culture and toxin detection assays have been described (agnoletti et al., ; bain et al., ; borriello and carmen, ; peeters et al., ) . c. spiroforme can be isolated from the intestinal contents of rabbits by high-speed centrifugation (holmes et al., ) . pcr assays for c. spiroforme and the iota toxin (binary toxin) have been developed (drigo et al., ) . differential diagnoses the differential diagnoses should include other clostridia, e. coli, viruses, and parasites (peeters et al., ) . treatment, prevention, and control the iota toxin from c. spiroforme is neutralized by serum prepared against the iota toxin of c. perfringens type e (borriello and carmen, ; carman and borriello, ; songer, ) . prevention, via reduction of risk factors and prudent use of antibiotics, is probably more important laboratory animal medicine than treatment (agnoletti et al., ) . cholestyramine has been used to prevent experimental enterotoxemia induced by clindamycin in rabbits (lipman et al., ) . fecal flora transplants using nonpathogenic c. spiroforme or c. difficile have been suggested for competitive inhibition of toxigenic strains (carman and evans, ) . no commercial vaccines are available for rabbits; however, vaccination of weanling rabbits with a toxoid imparted protection to intraperitoneal challenge with iota toxin (songer, ) . administration of antibiotics and change in diet are usually the treatment for c. spiroforme infections (songer, ) . the antibiotic susceptibility of c. spiroforme has been investigated (agnoletti et al., ; carman and wilkins, ) . c. spiroforme can have a wide range of resistance to antimicrobial classes used in rabbit therapy (agnoletti et al., ) . feeding fresh meadow hay has been suggested (bain et al., ) . research complications the mortality due to enterotoxemia caused by c. spiroforme would be disruptive to ongoing studies. no other complications have been reported. ii. clostridium difficile etiology c. difficile is a gram-positive, sporeforming, anaerobic bacillus commonly associated with diarrhea and colitis in humans and animals (keel and songer, ) . clinical signs c. difficile infection may be associated with anorexia, depression, diarrhea, fecal-staining of the perineum, decreased fecal output, abdominal distention, and death (perkins et al., ; rehg and lu, ) . peracute death, without clinical signs, is also a common presentation in rabbits (keel and songer, ; perkins et al., ) . epizootiology the spread of c. difficile involves carrier animals that do not show clinical signs of disease (keel and songer, ) . the carrier state may depend on the age of the individual (keel and songer, ) . c. difficile is thought to be acquired from the environment due to persistent contamination with spores (keel and songer, ) . disease is associated with antibiotic treatment but can also develop spontaneously (without antibiotic treatment) (perkins et al., ; rehg and lu, ) . the disease may also occur after stressful events such as weaning, sudden dietary changes, lactation, kindling, and illness (perkins et al., ) . rabbits that have been recently weaned are the most susceptible (perkins et al., ) . newborn rabbits are resistant to c. difficile disease possibly due to the lack of receptors for the toxins (keel and songer, ) . similar to c. spiroforme, the pathogenesis is associated with disruption of the gut flora and with colonization and proliferation of toxigenic clostridium. pathology grossly, a fluid-filled cecum and colon may be found on necropsy (rehg and lu, ) . spontaneous disease in rabbits is associated with lesions in the small intestine, most commonly in the ileum (keel and songer, ) . in one study, the small intestine was distended with fluid and the cecum was distended with chyme (perkins et al., ) . c. difficile is also associated with hemorrhagic typhlitis in hares (dabard et al., ) . c. difficile causes severe jejunal lesions in rabbits, but cecal lesions may occur (keel and songer, ; perkins et al., ) . mural hemorrhages, mucosal necrosis, and submucosal edema have been observed (perkins et al., ) . toxins a (enterotoxin) and b (cytotoxin) act synergistically and are essential virulence factors of c. difficile that enter the cells through receptor-mediated endocytosis (keel and songer, ) . toxins a and b disrupt the actin cytoskeleton by disrupting rho-subtype intracellular signaling molecules that affect cellular function (keel and songer, ) . inflammation and neurogenic stimuli also are involved in the pathogenesis of c. difficile disease (keel and songer, ) . in addition to toxins a and b, some c. difficile strains produce an actinspecific adp-ribosyltransferase or binary toxin (stubbs et al., ) . diagnosis c. difficile isolation and toxin assays have been described (keel and songer, ; perkins et al., ; rehg and lu, ) . c. difficile selective agar is commercially available. the tissue culture cytotoxin assay for c. difficile toxin b is considered the 'gold standard' (belanger et al., ) . c. difficile toxin b can be neutralized with c. sordelli antiserum, but not with c. spiroforme antiserum (perkins et al., ) . commercially available enzyme immunoassays to detect c. difficile toxin(s) have been used to diagnose rabbit cases (garcia et al., ; perkins et al., ) . pcr assays have been developed (belanger et al., ; goldenberg et al., ; houser et al., ; pallis et al., ) . differential diagnoses the differential diagnosis of peracute death in rabbits should include infection with clostridium spp. and/or ehec infection (garcia et al., ; perkins et al., ) . treatment, prevention, and control as with c. spiroforme, the reduction of risk factors and the prudent use of antibiotics are recommended (agnoletti et al., ) . cholestyramine may also be used for prevention (lipman et al., ) . fecal flora transplants have been suggested and commercial probiotic strains are able to inhibit c. difficile and c. perfringens in vitro (carman and evans, ; schoster et al., ) . research complications the sporadic nature of deaths due to c. difficile infection is unlikely to result in significant complications to research. iii. clostridium perfringens c. perfringens type e produces alpha and iota toxins and is an laboratory animal medicine uncommon cause of enterotoxemia in rabbits (redondo et al., ; songer, ) . because of the similarity between the iota toxins of c. spiroforme and c. perfringens type e, detection of toxin alone for diagnostic purposes will not differentiate between the two organisms (songer, ) . pcr can be used for typing c. perfringens based on amplification of toxin genes (daube et al., ) . historically, a disease process associated with e. coli infection was known as colibacillosis. currently, e. coli is classified based on the virulence factors that are genetically encoded and expressed in the bacteria. different virulence factors are associated with different e. coli 'pathotypes'. pathotypes may be associated with three general clinical syndromes: enteric/diarrheal disease, urinary tract infections, and sepsis/meningitis (kaper et al., ) . the centers for disease control and prevention currently recognizes six pathotypes associated with diarrhea in humans: enteropathogenic e. coli (epec), shiga toxin (stx)-producing e. coli (stec; also known as enterohemorrhagic e. coli (ehec) or verocytotoxin-producing e. coli (vtec)), enterotoxigenic e. coli (etec), enteroaggregative e. coli (eaec), enteroinvasive e. coli (eiec), and diffusely adherent e. coli (daec) (http://www.cdc.gov/ecoli/general/). comparative genomic analyses identified genes that were isolateand pathovar-specific and clustered strains according to pathotypes (lukjancenko et al., ; rasko et al., ) . two more emerging pathotypes have been suggested: adherent invasive e. coli (aiec; associated with crohn's disease in humans) and shiga toxin-producing enteroaggregative e. coli (steaec; associated with a large outbreak of hemolytic uremic syndrome (hus) in europe) (clements et al., ) . of these pathotypes, epec and stec are associated with natural disease in rabbits (cantey and blake, ; garcia et al., ) . in addition, necrotoxigenic e. coli (ntec) are associated with disease in rabbits (blanco et al., ) . pathogenic animal and human strains are very closely related and have virulence genes in common (clermont et al., ) . therefore, it is important to determine which e. coli pathotype(s) are associated with disease in rabbits in order to characterize new diseases and/or more accurately diagnose, prevent, control, and treat the condition as well as for epidemiological investigations. etiology epec carry the eae gene that encodes intimin, a protein involved in induction of attaching and effacing lesions in the intestine. e. coli serotype o , also known as rdec- , is the prototype epec strain which was isolated from rabbits with diarrhea and has been used experimentally as a model to study epec-induced disease (cantey and blake, ) . epec is an important cause of potentially fatal infant diarrhea in developing countries (kaper et al., ; swennes et al., ) . clinical signs ehec o was isolated from an outbreak of bloody diarrhea and sudden death in dutch belted rabbits (fig. . ) (garcia et al., ) . acute diarrhea following shipment was associated with epec o :h infection in laboratory rabbits (swennes et al., ) . laboratory rabbits can be reservoir hosts of pathogenic e. coli without exhibiting clinical signs (garcía and fox, ; swennes et al., ) . patent or occult blood may be detected in the feces of infected rabbits (camguilhem and milon, ; garcia et al., ) . epizootiology epec and ehec can be enzootic in rabbit colonies and these bacteria are transmitted by the fecal-oral route (garcía and fox, ; swennes et al., ; swennes et al., ) . epec and ehec coinfections are possible (garcía and fox, ; garcia et al., ) . ehec are a subset of stec that carry stx gene(s) that encode stx(s) and also carry the eae gene that encodes intimin (melton-celsa et al., ) . rabbits can harbor stec strains and are recognized as their vectors and reservoir hosts (bailey et al., ; blanco et al., ; garcía and fox, ; kim et al., ; leclercq and mahillon, ; pohl et al., ; pritchard et al., ; scaife et al., ) . pathology grossly, paintbrush hemorrhages of the cecal serosa may be observed after experimental infection with epec (camguilhem and milon, ) . also, experimentally, the serosal surface of the cecum and/or proximal colon can develop petechial or echymotic hemorrhages and may become edematous and thickened (garcía et al., ) . histologically and ultrastructurally, attaching and effacing lesions with pedestal formation can be observed with epec or ehec infections (kaper et al., ; peeters et al., ) . enterocolitis, nephropathy, and thrombotic microangiopathy can be observed in ehec-infected rabbits (garcía et al., ) . diagnosis feces or intestinal contents can be enriched in broth and then cultured using blood agar, macconkey agar, or ehec-selective media such as sorbitol macconkey agar or raibow® agar (garcía and fox, ; tarr, ; tarr et al., ) . after isolation of e. coli in pure culture, samples can be biotyped using commercial methods such as the api® e strips (bio-mérieux). serotyping and molecular characterization of isolates can be performed by the e. coli reference center (http://ecoli.cas.psu.edu/) at the pennsylvania state university. pcr assays can be utilized to detect virulence factors characteristic of epec, ehec, or other pathogenic e. coli as well as for high-resolution genotyping for epidemiological studies (blanco et al., ; garcía and fox, ) . molecular characterization of stec strains can be performed by the stec center (http://www. shigatox.net/new/) at michigan state university. differential diagnoses the differential diagnoses should include other causes of diarrhea in rabbits including the clostridial diseases and intestinal coccidiosis. treatment, prevention, and control for prevention, avoid introduction of rabbits of unknown pathogenic e. coli status into a colony. rabbits should be screened by culture and e. coli isolates characterized for virulence factors by pcr. also, since it is known that ehec can contaminate plants and vegetables, laboratory personnel should be aware that rabbit feeds such as hay, alfalfa, and other greens have the potential to introduce enteric pathogens such as ehec into laboratory rabbits (berger et al., ; garcía and fox, ) . ehec o can survive for days in grass hay feed (davis et al., ) . cesarean section rederivation and antibiotic treatment have been suggested for eradication of pathogenic e. coli in rabbits (swennes et al., ) . a 'one health' approach should be incorporated to control ehec infections because outbreaks such as with ehec o in humans was linked to consumption of spinach contaminated by feral swine and was additionally isolated from domestic cattle, surface water, sediment, and soil (garcia et al., ) -a good example of integrating human, animal, and environmental health (monath et al., ) . antibiotic treatment should be based on culture and sensitivity. importantly, in humans infected with ehec, treatment with antibiotics is controversial due to the possibility of induction of stx-encoding bacteriophages and worsening of the clinical condition due to hemolytic uremic syndrome (tarr et al., ) ; therefore, antibiotic treatment of rabbits infected with ehec may not be recommended. clinically affected rabbits can be treated with fluids as this intervention is nephroprotective in humans (hickey et al., ) . in addition, rabbit epec strains may carry extended-spectrum beta-lactamases making them resistant to antibiotics (poeta et al., ) . parenteral enrofloxacin administered prior to shipment decreased morbidity and mortality associated with endemic epec (swennes et al., ) . research complications epec infection can cause high morbidity and mortality in laboratory rabbit colonies and can affect studies involving intestinal physiology in rabbits. epec and ehec present a zoonotic risk (garcia et al., ; poeta et al., ; swennes et al., ) . etiology treponema paraluiscuniculi is a noncultivable species that infects rabbits and causes venereal spirochetosis or treponematosis (also known as rabbit syphilis, vent disease, or cuniculosis) (smajs et al., ) . although its genome structure is closely related to other pathogenic treponema species including t. pallidum subsp. pallidum, the etiological agent of human syphilis, t. paraluiscuniculi does not infect humans (smajs et al., ) . genome sequencing revealed that t. paraluiscuniculi evolved from a t. pallidum-like ancestor and adapted to rabbits during loss of infectivity to humans (smajs et al., ) . t. paraluiscuniculi can also infect hares, and causes seroconversion, but no clinical signs. in contrast, the related organism, t. paraluisleporis, can infect and induce disease in rabbits and hares. the close phylogenetic association between t. paraluiscuniculi and t. paraluisleporis suggests that these organisms could be given a subspecies or ecovar status rather than species status (lumeij et al., ) . clinical signs in naturally infected rabbits lesions commonly occur in the vulva or prepuce (cunliffe-beamer and fox, a) . other parts of the body that may be affected, in descending order, include the anal region, nose, eyelid, and lip (cunliffe-beamer and fox, a) . naturally infected rabbits develop lesions of the ear, face, prepuce, and anus (small and newman, ) . in a study involving intratesticular inoculation of t. paraluiscuniculi, single lesions were found in the prepuce or scrotum and multiple lesions were found in the nose, mouth, ear, prepuce, foot, and scrotum (small and newman, ) . all lesions had abundant treponemes by dark-field examination (small and newman, ) . epizootiology susceptibility to, and expression of venereal spirochetosis, may vary with the strain of rabbit (cunliffe-beamer and fox, b) . the prevalence of t. paraluiscuniculi infection increased with parity in adult females and most adult males seroconverted within months of entering the breeding program. these findings suggested that t. paraluiscuniculi spreads by horizontal transmission in adult rabbits (digiacomo et al., ) . in an enzootically infected conventional rabbit colony, the frequency of venereal spirochetosis was lower in rabbits less than months of age than in adult rabbits (cunliffe-beamer and fox, b) . experiments involving cross fostering of newborns indicated that infection occurred at birth (vertical transmission) and during the suckling period (cunliffe-beamer and fox, b) . in addition, horizontal transmission by coitus and skin contact occurs (small and newman, ) . experimental topical or intradermal-subcutaneous genital inoculation of adult rabbits confirmed these routes of transmission (cunliffe-beamer and fox, b) . the t. pallidum repeat (tpr) genes in t. pallidum subsp. pallidum are thought to code for potential virulence factors. tprk was the only tpr homolog found in t. paraluiscuniculi that induced antibody and t cell responses after experimental inoculation of rabbits indicating that tprk may be an important virulence factor in venereal spirochetosis (giacani et al., ) . virulence factors and pathogenesis have been recently reviewed (smajs et al., ) . pathology the lesions include erythemathous macules or papules to erosions, ulcers, and crusts (cunliffe-beamer and fox, a) . diagnosis serologic tests that have been used include the nontreponemal antigen tests (venereal disease research laboratory (vdrl) and rapid plasma reagin), microhemagglutination, and fluorescent treponemal antibody absorption tests (digiacomo et al., ) . although the nontreponemal antigen tests were not completely satisfactory, the vdrl test was more sensitive and the plasma reagin test was more specific in detecting t. paraluiscuniculi infection (digiacomo et al., ) . the sensitivity and specificity of the microhemagglutination test compared favorably with the fluorescent treponemal antibody absorption test and was recommended as the optimal assay to make a diagnosis (digiacomo et al., ) . detection of t. paraluiscuniculi in lesions can be achieved by dark-field microscopic examination of scrapings from lesions and by histological evaluation of silver-stained testicular sections (cunliffe-beamer and fox, a; faine, ) . pcr has been used for molecular characterization of treponemes including t. paraluiscuniculi (cejkova et al., ) . differential diagnoses the skin lesions may be confused with abrasions (trauma), mycotic infections, and lesions of ectoparasites (acariasis) (small and newman, ) . treatment, prevention, and control there are no vaccines available at this time to prevent treponematosis in rabbits; however, rabbits have been used as experimental models to test vaccines against t. pallidum in humans (ho and lukehart, ) . hysterectomy derivation can eliminate venereal spirochetosis (cunliffe-beamer and fox, b) . a study investigating two different doses ( , or , iu/kg body weight/ week) of benzathine penicillin g-procaine penicillin g to treat rabbits at -day intervals found that both dosages were effective. lesions healed within weeks of the first treatment and the plasma reagin titers declined markedly or disappeared by the sixth week after the first treatment (cunliffe-beamer and fox, c) . research complications t. paraluiscuniculi can affect studies of t. pallidum in rabbits (small and newman, ) . partial immunological cross-protection has been observed between t. paraluiscuniculi and t. pallidum (smajs et al., ; turner and hollander, ) . etiology lawsonia intracellularis is a gram-negative, curved to spiral-shaped, obligate intracellular bacterium that causes proliferative enteropathy in rabbits and other species of animals (sait et al., ; schauer et al., ) . clinical signs an intraepithelial 'vibrio' was associated with acute typhlitis in rabbits - weeks after weaning (moon et al., ) . diarrhea was reported in japanese white rabbits with presumptive l. intracellularis infection and histiocytic enteritis (umemura et al., ) . in another report, sucklings and weanlings were affected and the feces of most of the rabbits were characterized as semifluid and mucinous or pasty, and three rabbits had watery diarrhea (schoeb and fox, ) . these affected rabbits were afebrile and lethargic, refused food and water, and most died within a few days after the onset of diarrhea (schoeb and fox, ) . diarrhea, depression, and dehydration that resolved over the course of - weeks were reported in -to -week-old new zealand white (nzw) rabbits (hotchkiss et al., ) . diarrhea and weight loss were reported in a -month-old rabbit (horiuchi et al., ). an outbreak of diarrhea with high ( %) mortality was reported in -to -month-old nzw rabbits with proliferative enterocolitis associated with l. intracellularis and epec (schauer et al., ) . epizootiology proliferative enteropathy generally occurs as isolated cases or occasional minor outbreaks in species other than the pig, blue fox, and hamster (lawson and gebhart, ) . infected rabbits can serve as reservoir hosts for l. intracellularis infection in other species including foals (pusterla et al., a (pusterla et al., , . however, l. intracellularis appears to adapt to the specific animal species it infects (vannucci et al., ) . the pathogenesis of l. intracellularis infection has been reviewed (lawson and gebhart, ; smith and lawson, ) . studies using interferon (ifn)-gamma receptor knockout mice determined that interferon ifngamma plays a significant role in limiting intracellular infection and increased cellular proliferation associated with l. intracellularis infection (smith et al., ) . lawsonia surface antigen (lsaa) plays a role during l. intracellularis attachment to and entry into intestinal epithelial cells (mccluskey et al., ) . balb/ca mice are susceptible to rabbit l. intracellularis isolates but not to pig l. intracellularis isolates suggesting that there are biological differences between the proliferative enteropathy isolates from rabbits and pigs (murakata et al., ) . pathology distention and diffuse mucosal thickening of the jejunum and proximal ileum with enlarged cranial mesenteric lymph nodes was observed in -to -month-old rabbits (umemura et al., ) . thickening of the mucosa was associated with distention of the lamina propria with macrophages and the enlargement of the lymph nodes was also associated with infiltration of macrophages (umemura et al., ) . minute bacilli were observed in the apical cytoplasm of mucosal epithelial cells using toluidine blue (umemura et al., ) . thickening of the cecum and proximal colon has also been reported (hotchkiss et al., ) . in another study, no gross lesions were found in the small intestine, but two suckling rabbits had reddened ceca with congested vessels (schoeb and fox, ) . in this study two types of microscopic lesions were characterized: ( ) erosive and suppurative cecitis and colitis, and ( ) proliferative lesions in the cecum, sacculated colon, ileum, and distal jejunum, or a combination of these (schoeb and fox, ) . some animals had both erosive and proliferative lesions. narrow curved or spiral bacteria were detected in rabbits with erosive and proliferative lesions using warthin-starry stain and these bacteria were more abundant in cases with severe lesions (schoeb and fox, ) . proliferative intestinal lesions contained curved to spiral argyrophilic intracellular bacteria in the apical cytoplasm of crypt enterocytes (hotchkiss et al., ) . diagnosis the s ribosomal dna sequences from l. intracellularis isolates from different species of animals are highly similar (cooper et al., a) . however, antigenic differences have been found between pig and rabbit isolates . the complete genome sequence of a porcine strain has been recently reported (sait et al., ) . l. intracellularis can be detected in feces from healthy and diarrheic rabbits (lim et al., ) . pcr assays to detect l. intracellularis dna in feces have been evaluated (pedersen et al., ) . these assays can be used for ante mortem diagnosis of proliferative enteropathy in pigs (pedersen et al., ) . pcr primers used to diagnose lawsonia in other animals species have been used in rabbit cases (cooper et al., b; duhamel et al., ; fox et al., ; horiuchi et al., ; hotchkiss et al., ; jones et al., ) . other diagnostic methods include enzyme-linked immunosorbent assay (elisa) using synthetic peptides of lsaa and immunomagnetic separation using anti-lsaa antibody to capture l. intracellularis in fecal samples followed by detection with atp bioluminescence (watarai et al., (watarai et al., , . in tissue sections, l. intracellularis can be detected using silver stains such as warthin-starry stain (duhamel et al., ; horiuchi et al., ; hotchkiss et al., ; schauer et al., ; schoeb and fox, ) . indirect immunofluorescence has also been used in deparaffinized intestinal sections from infected rabbits (schoeb and fox, ) . immunohistochemistry using antiserum against synthetic peptides of lsaa has also been used to detect l. intracellularis in the ileum of a naturally infected rabbit (watarai et al., ) . electron microscopy reveals organisms that are ~ . - . μm wide and ≤ . μm long in the apical cytoplasm of villous and crypt epithelial cells (duhamel et al., ) . l. intracellularis can be cultured from homogenized intestinal tissue in cell lines including iec- (rat small intestinal cells) and mccoy cells (mouse fibroblasts) (lawson and gebhart, ; watarai et al., ) . a quantitative pcr (qpcr) assay that is able to assess the growth of l. intracellularis in cultured cells has also been used to detect the organisms in pig fecal samples and could be used in other animal species (drozd et al., ) . differential diagnoses clinically, the differential diagnosis should include other causes of diarrhea in rabbits. mycobacterium avium subsp. paratuberculosis can infect rabbits and induce thickening of the intestinal mucosa (beard et al., ; greig et al., ) . therefore, rabbit intestinal sections should be examined for acidfast organisms using stains such as ziehl-neelsen stain (duhamel et al., ; horiuchi et al., ; schoeb and fox, ; umemura et al., ) . furthermore, other intestinal organisms may colonize the intestine during l. intracellularis infection in rabbits (duhamel et al., ; hotchkiss et al., ; lim et al., ; schauer et al., ) . other bacterial diseases have been sporadically reported in rabbits. these are summarized in table . . treatment, prevention, and control vaccination strategies have been tested and developed for pigs and horses, but not for rabbits (nogueira et al., ; pusterla et al., b; weibel et al., ) . testing rabbits by pcr prior to introduction to a laboratory colony may be necessary for exclusion of this organism. oral neomycin ( mg/rabbit) was used to treat surviving rabbits during an outbreak of presumptive l. intracellularis and the diarrhea subsided (umemura et al., ) . because l. intracellularis infects the intestine and ifn-gamma appears to be involved in pathogenesis, research involving rabbit gastrointestinal pathology and immune responses may be confounded by infection with this organism. research complications the mortality associated with l. intracellularis infection would be disruptive to ongoing studies. etiology myxomatosis is caused by myxoma virus, a member of the family poxviridae, genus leporipoxvirus (kerr and donnelly, ; spiesschaert et al., ) . clinical signs the severity of disease varies with the strain of virus and the host species and breed. rabbits of the genus oryctolagus are particularly susceptible and often develop a fatal disease characterized by mucinous skin lesions and tumors. affected animals also exhibit edema around the mouth, nose, anus, and genitals as well as progressive conjunctivitis with serous and mucopurulent secretions from the eyes and nose (brabb and di giacomo, ; kerr and donnelly, ; spiesschaert et al., ) . bacterial pneumonia commonly develops and animals die - days after infection. the virus is spread by arthropod vectors and direct contact. epizootiology myxomatosis has a worldwide distribution. various species of sylvilagus and lepus are naturally susceptible (brabb and di giacomo, ) . the myxoma virus genome encodes for a number of immunomodulatory proteins which greatly affect the host immune response by inhibiting apoptosis, interfering with leukocyte chemotaxis, and suppressing leukocyte activation, thereby fostering viral replication and spread (spiesschaert et al., ) . pathology histopathology shows these 'myxomas' to be composed of undifferentiated stellate mesenchymal cells embedded in a matrix of mucinous material and interspersed with capillaries and inflammatory cells (brabb and di giacomo, ; kerr and donnelly, ) . diagnosis diagnosis can be made by pcr or elisa. definitive diagnosis depends on culture of the virus from infected tissues. differential diagnoses rabbits of the genus sylvilagus develop fibroma-like lesions that may be indistinguishable from those caused by rabbit fibroma virus. the two diseases have been distinguished by inoculation of fibroma material into oryctolagus rabbits. they develop fatal disease if the myxoma virus is the etiologic agent, or fibromas if rabbit fibroma virus is responsible. treatment, prevention, and control since the disease is spread by fleas and mosquitoes as well as by direct contact, control measures should include prevention of contact with arthropods and quarantine of infected rabbits. vaccines have been used in europe with some success. most recently, a live recombinant vaccine for both myxomatosis and rabbit hemorrhagic disease has been released in the united kingdom (spibey et al., ) . research complications none have been reported. rabbit (shope) fibroma virus is a leporipoxvirus that is antigenically related to myxoma virus. fibromatosis is endemic in wild rabbits; however, an outbreak in commercial rabbits caused extensive mortality (joiner et al., ) . usually, less virulent strains cause skin tumors in domestic rabbits (raflo et al., ) . the disease is probably spread by arthropods (brabb and di giacomo, ; kerr and donnelly, ) . fibromas are flat, subcutaneous, easily movable tumors, and most often found on the legs and face. tumors may persist for some time but eventually regress. metastasis does not occur. rabbit pox is a rare disease induced by an orthopoxvirus taxonomically similar to vaccina virus that has caused outbreaks of fatal disease in laboratory rabbits in the united states and holland (brabb and di giacomo, ) . rabbits with the disease may or may not present with 'pox' lesions in the skin. the animals have a fever and nasal discharge or days after infection. most rabbits have eye lesions including blepharitis, conjunctivitis, and keratitis with subsequent corneal ulceration. skin lesions, when present, are widespread. they begin as a macular rash and progress to papules up to cm in diameter by days postinfection. the lymph nodes are enlarged, the face is often edematous, and there may be lesions in the oral and nasal cavity. at gross necropsy, nodules can be found in the liver, gall bladder, spleen, lung, and reproductive organs. necrosis is widespread. characteristic cytoplasmic inclusions seen in many poxvirus infections are rare in this disease. mortality is high in affected animals. the virus is apparently spread by aerosols and is difficult to control. rabbit pox is used as a model of smallpox in humans in response to the potential use of smallpox as a bioterrorism agent. it is an effective model for the evaluation of potential therapies against smallpox (nalca and nichols, ; rice et al., ) . four herpesviruses (leporid herpesviruses , , , and ) have been isolated from rabbits and hares (davison, ) . leporid herpesvirus (lhv- ) was isolated from cottontail rabbits and is also known as cottontail rabbit herpesvirus. it is not pathogenic for domestic rabbits. lhv- (herpesvirus cuniculi) was isolated from domestic rabbits (o. cuniculus) and causes subclinical infections. lhv- (herpesvirus sylvilagus) was isolated from cottontail rabbits. cottontail rabbits infected with the virus develop a lymphoproliferative disease with lymphoid infiltration of many organs (hesselton et al., ) . lhv- does not infect domestic rabbits. lhv- - are tentatively classified in the genus radinovirus, subfamily gammaherpesvirinae. lhv- was isolated from domestic rabbits and caused severe disease in preweanlings (jin et al., a, b) . clinical signs included weakness, anorexia, conjunctivitis, keratitis, and periocular swelling. some animals also developed skin ulcers. lhv- is genus simplexvirus, subfamily alphaherpesvirinae. the cottontail rabbit is the natural host of the cottontail (shope) papillomavirus, a kappapapillomavirus, laboratory animal medicine which causes horny warts primarily on the neck, shoulders, and abdomen. the disease has a wide geographic distribution with the highest incidence occurring in rabbits in the midwest (brabb and di giacomo, ) . as many as % of infected sylvilagus rabbits develop squamous cell carcinomas. natural outbreaks in domestic rabbits have been reported (hagen, ) . in these natural outbreaks, papillomas were more common on the eyelids and ears. the virus is transmitted by arthropod vectors. this virus is used extensively as a model for the study of oncogenic virus biology and as a model for the treatment and prevention of papillomavirus infections in humans (christensen, ; salmon et al., ; sundarum et al., ) . oral papillomatosis in domestic rabbits is caused by a kappapapillomavirus that is related to but distinct from the cottontail rabbit papilloma virus. naturally occurring lesions have been seen in laboratory rabbits and appear as small, white, discrete growths on the ventral surface of the tongue (kerr and donnelly, ) . lesions may ulcerate. microscopic examination shows them to be typical papillomas. most lesions eventually regress spontaneously (brabb and di giacomo, ; kerr and donnelly, ) . etiology rabbit rotavirus is a member of the family reoviridae. all isolates of rabbit rotavirus have been classified as group a and have been serotype (brabb and di giacomo, ; kerr and donnelly, ) . clinical signs the severity of disease in naturally occurring outbreaks has been variable. in severe outbreaks, affected animals exhibit anorexia, dehydration, and watery to mucoid diarrhea and mortality can be quite high. in other reported outbreaks, mild, transient diarrhea has been reported (brabb and di giacomo, ; kerr and donnelly, ) . similarly, attempts to experimentally produce clinical disease have had variable results. mild diarrhea is usually seen, but in some studies there has been significant mortality. it is probable that other factors, such as maternal antibodies, diet, and the presence of pathogenic bacteria, affect the severity of clinical disease in outbreaks. for example, in combined experimental infections with both rotavirus and e. coli, the inoculation of both organisms led to more serious clinical signs than when given alone, indicating that rotavirus may have been a more significant determinant in the manifestation of this disease (thouless et al., ) . these investigators also showed that older rabbits were naturally more resistant to the combined infection with rotavirus and e. coli. epizootiology rotavirus infections of domestic rabbits are common (brabb and di giacomo, ) . many colonies of rabbits are serologically positive, and rotavirus can be isolated readily from rabbit feces. in endemically infected colonies, maternal antibodies to rotaviruses are passed transplacentally and decline at around the time of weaning (brabb and di giacomo, ) . rabbits of weaning age are most susceptible. very young rabbits appear to be protected from rotavirus infection by passive immunity, when present, but are quite susceptible when there is none (schoeb et al., ) . this is also the time when they are most likely to be subjected to diet changes that may contribute to a change in microbial flora. pathology in affected animals, there is villous atrophy and loss of epithelial cells in the small intestines. a lymphocytic infiltrate is present. diagnosis immunoassays (elisa and multiplex fluorescent immunoassay) are commercially available for rabbit rotavirus. a commercial immunochromatography kits for detecting human rotavirus infection was used successfully to diagnose rabbit rotavirus infection (fushuku and fukuda, ) . differential diagnoses c. piliforme, c. spiroforme, c. difficile, e. coli, lawsonia intracellularis, coronavirus, coccidiosis, and intestinal parasites should be considered. research complications colony mortality would be disruptive to ongoing studies. pleural effusion disease/infectious cardiomyopathy was diagnosed in rabbits inoculated with t. palliduminfected stocks of testicular tissue. because these treponemes could not be grown in vitro, the organism was propagated by passage in rabbits. the stocks were contaminated with a coronavirus, although it is not known whether this virus originated from rabbits or was a virus of human origin that had adapted to rabbits. with continued passage, the virus became more virulent, and significant mortality ensued. evidence indicated that it was not transmitted by direct contact. rabbits died due to congestive heart failure, and microscopic examination showed there was widespread necrosis of the heart muscle. it has been suggested that infection with this virus might be a model for the study of virus-induced cardiomyopathy (brabb and di giacomo, ; kerr and donnelly, ) . rabbit enteric coronavirus has been isolated from tissue cultures from rabbits (brabb and di giacomo, ; kerr and donnelly, ; lapierre et al., ) and has been associated with one naturally occurring outbreak of diarrhea in a barrier-maintained breeding colony (eaton, ) . these rabbits developed severe diarrhea, and most died within h of onset of clinical signs. attempts to reproduce the disease led to watery diarrhea, which lasted a short time; however, none of the rabbits died. it is quite probable that other microorganisms or laboratory animal medicine unknown environmental factors contributed to the severity of this outbreak. etiology rabbit hemorrhagic disease virus is a calicivirus of the genus lagovirus and is the causative agent of rabbit hemorrhagic disease (rhd) (abrantes et al., ; brabb and di giacomo, ; kerr and donnelly, ) . clinical signs three clinical syndromes are seen (abrantes et al., ) . the peracute form is characterized by sudden death without clinical signs. acutely affected animals demonstrate anorexia and depression. in addition, neurologic signs, respiratory signs, ocular hemorrhage, and epistaxis may be seen. morbidity and mortality are extremely high. lymphopenia and abnormalities in coagulation parameters are also seen. in the subacute form, similar signs may occur but are considerably milder and most of these rabbits survive (abrantes et al., ; kerr and donnelly, ) . epizootiology rabbit hemorrhagic disease was first reported in china in and is currently endemic in europe, asia, africa, australia, and new zealand. in addition, isolated outbreaks have been reported in numerous countries. the virus is transmitted by the fecal-oral route. the role of fomites and arthropod vectors is also suspected (brabb and di giacomo, ; kerr and donnelly, ) . the incubation period may be as short as or days, and sudden death with no previous signs is common. pathology periportal hepatic necrosis is the only consistent microscopic lesion, and the animals die due to disseminated intravascular coagulopathy and thrombosis (abrantes et al., ; kerr and donnelly, ) . diagnosis the virus has not been successfully grown in vitro; however, diagnosis can be confirmed with negative-contrast electron microscopy of liver tissue. specific antibodies can be detected by elisa or by hemagglutination inhibition. differential diagnoses a related calicivirus, european brown hare virus, has caused disease in hares in several countries in europe (brabb and di giacomo, ) . animals present with necrotic hepatitis, hemorrhages in the trachea and lungs, and pulmonary edema. a monoclonal antibody elisa is available for serodiagnosis, and control measures are similar to those for rhd. the agent resists drying, can be carried on fomites, and may be transmitted via respiratory and intestinal secretions (mitro and krauss, ) . any rabbit colonies with this disease should be quarantined and depopulated, and the environment thoroughly cleansed and disinfected. research complications colony mortality would be disruptive to ongoing studies. other viral infections several other viruses have been isolated from rabbit tissues, but have not been shown to produce disease. these include paramyxoviruses and bunyaviruses. serologic titers to togaviruses and flaviviruses have also been demonstrated in rabbits (brabb and di giacomo, ; kerr and donnelly, ) . etiology hepatic coccidiosis is caused by the parasite eimeria stiedae, which has also been referred to as monocystis stiedae, coccidium oviforme, and c. cuniculi (hofing and kraus, ) . clinical signs the clinical disease has a wide range of manifestations. mild infections often result in no apparent disease. most clinical signs are the result of interruption of normal hepatic function and blockage of the bile ducts. these signs are more common in juvenile rabbits and can include hepatomegaly, icterus, and anorexia (schoeb et al., ) . diarrhea can occur at the terminal stages of the disease (hofing and kraus, ) . decreased growth rates and weight loss are common. joyner et al. ( ) demonstrated that infected rabbits begin to lose weight within days. enlargement of the liver (hepatomegaly) is common. the liver normally is approximately . % of the body weight, but rabbits with severe hepatic coccidiosis may have livers that contribute to greater than % of the body weight (lund, b) . the age of the host strongly affects parasite development and oocyst production. four-month-old, coccidia-free rabbits experimentally infected with e. stiedae produced fewer oocysts than similarly infected -monthold rabbits (gomez-bautista et al., ) . epizootiology e. stiedae is found worldwide, although rabbits bred for use in research are commonly free of the parasite. transmission occurs by the fecaloral route, as for other coccidia. the organism has also been experimentally transmitted by intravenous, intraperitoneal, and intramuscular administration of oocysts (pellérdy, ) . smetana ( ) demonstrated that infection of the entire liver occurred following ligation of the right bile duct and inoculation of e. stiedae oocysts. the study also showed that infection occurred earliest within the small intrahepatic ducts, leading to the theory that infection occurred via blood or lymph. the precise life cycle is still undetermined, although a number of studies have examined it (horton, ; owen, ; rose, ) . sporozoites have been demonstrated in the lymph nodes following experimental inoculation (horton, ; rose, ) . pathology necropsy often shows the liver to be enlarged and discolored, with multifocal yellowish laboratory animal medicine white lesions of varying size (fig. . ) . exudate in the biliary tree is common, along with dilatation of bile ducts. microscopically, papillomatous hyperplasia of the ducts along with multiple life-cycle stages of the organism can be observed in the biliary epithelium ( fig. . ) . diagnosis infected rabbits may have decreased fibrinogen when compared to uninfected rabbits (cam et al., ) . serum bilirubin levels can rise to mg/ dl, increasing as soon as day of infection and increasing through days - before moderating (rose, ) . leukocytosis and anemia can be observed and acute phase proteins are notably increased by days post infection (freitas et al., ) . diagnosis can be made by examination of fecal material, by either flotation or concentration methods. oocysts can also be detected within the gallbladder exudate (hofing and kraus, ) . alternatively, oocysts can sometimes be observed by microscopic examination of impression smears of the cut surface of the liver. ultrasonography may be a useful tool for diagnosis, with dilated vessels and bile ducts and increased echogenicity of the liver parenchyma (cam et al., ) . differential diagnoses the hyperplastic biliary ducts can be mistaken grossly for neoplasia. other types of parasitic hepatitis should be considered as differential diagnoses. less frequently, hepatitis secondary to bacterial infections can occur. treatment, prevention, and control control of the infection until development of natural immunity is one strategy to minimize the severity of disease. davies et al. ( ) demonstrated that immunity occurs following a light infection with e. stiedae. in the rabbit, immunity to eimeria may be lifelong (niilo, ; pellérdy, ) . prevention of hepatic coccidiosis with sulfaquinozaline in the feed ( ppm) was shown to prevent infection when experimental challenged with , sporulated oocysts (joyner et al., ) . sulfonamides have been shown effective against eimeria spp. (hagen, ; horton-smith, ; jankiewicz, ; lund, a; tsunoda et al., ) . treatment with toltrazuril ( ppm in drinking water for one day) has been shown to effectively treat infected animals (cam et al., ) . thorough sanitation of potentially contaminated surfaces is critical to control of coccidiosis. research complications potential research complications arising from hepatic coccidiosis are considerable. the resulting liver damage and decreased weight gains can complicate both the supply of rabbits for research as well as adversely affect research protocols. etiology there are at least different pathogenic species of intestinal coccidia in rabbits, including eimeria coecicola, e. elongate, e exigua, e. intestinalis, e. flavescens, e. irresidua, e. magna, e. matsubayashii, e. media, e. nagnurensis, e. neoleporis, e. piriformis, e. vejdovskyi, and e. perforans (pakandl, ). all of these coccidia are presented here as a group rather than as individual species of intestinal coccidia. clinical signs although intestinal coccidiosis may be subclinical, clinical signs can range from mild to severe and can result in death of the animal. postweanling rabbits are the most likely to experience mortality related to intestinal coccidiosis. suckling rabbits (< days old) are generally considered to be resistant to infection (pakandl and hlaskova, ) . clinical signs also depend on the species of coccidia that are present. severe diarrhea, weight loss, or mild reduction in growth rate are all laboratory animal medicine possibilities. fecal occult blood may be detected with e. perforans infection (li and ooi, ) . death is usually associated with severe dehydration subsequent to diarrhea (frenkel, ) . epizootiology intestinal coccidiosis is a common rabbit disease worldwide (varga, ) . transmission is by the fecal-oral route through ingestion of sporocysts. unsporulated oocysts are passed in the feces and are not infective. such oocysts will, however, sporulate to an infective stage within days after shedding; thus, it is important that sanitation be frequent enough to remove infective stages from the environment. the oocyst burden of feces can be enormous. gallazzi (gallazzi, ) demonstrated that a subclinical carrier of intestinal coccidia had , oocysts/gram of feces and that a rabbit with diarrhea could shed in excess of , oocysts/gram of feces. environmental contamination with oocysts can be a problem when large numbers of oocysts are being excreted. the life cycles of eimeria spp. are similar to those of other coccidia. schizogony, gametogony, and sporogony are the three phases of this life cycle. other sources can be consulted for greater detail on the life cycle of these protozoans (davies et al., ; pakandl, ; pakandl and jelinkova, ; pellérdy, ; rutherford, ) . pathology lesions are apparent in the small and large intestines. necrotic areas of the intestinal wall appear as white foci (pakes, ; pakes and gerrity, ) . the location and extent of the lesions depend on the species of coccidia. diagnosis diagnosis of intestinal coccidiosis can be made through identification of the oocysts in the feces (pakes and gerrity, ) . a pcr has been developed (oliveira et al., ) that differentiates between of the different eimeria species that infect the domestic rabbit. this test has excellent sensitivity, with the ability to detect . - . sporulated oocysts per sample. smaller scale pcr for detection and differentiation between the more pathogenic species (e. intestinalis, e. flavicenens, and e. stiedae) has also been developed (yan et al., ) . differential diagnoses other causes of diarrhea in rabbits should be considered including tyzzer's disease, the clostridial diseases, colibacillosis, l. intracellularis, enteric coronovairus and rotavirus, protozoons, or intestinal parasites. treatment, prevention, and control because intestinal coccidiosis is most common in postweanling rabbits, prevention of the disease should focus on the preweaning period. an oral vaccination has been developed and consists of a nonpathogenic strain of e. magna. this vaccine is sprayed into the nest box when rabbits are days of age. the preweanling rabbits develop immunity subsequent to infection with the nonpathogenic strain and are then resistant to wild-type strains of e. magna at days of age (drouet-viard et al., ) . other oral vaccines developed from various eimeria strains are also in development (akpo et al., ) . prevention and control of infection can be accomplished by providing . % sulfamerazine or . % sulfaquinoxaline in the drinking water (kraus et al., ) . a combination of sulfaquinoxaline, strict sanitation, and elimination of infected animals has been shown to eliminate intestinal coccidiosis from a rabbit breeding colony (pakes and gerrity, ) . as for hepatic coccidiosis, sulfaquinoxaline provided in the feed ( ppm) is an effective treatment. research complications intestinal coccidiosis can impact studies of the gastrointestinal tract, or have an impact on survival of postweanling rabbits. etiology the protozoan organism cryptosporidium cuniculus has been found in the intestinal tract of the rabbit (hadfield and chalmers, ; inman and takeuchi, ; kaupke et al., ; rehg et al., ; robinson et al., ; shiibashi et al., ; zhang et al., ) . clinical signs clinical signs related to cryptosporidiosis seem to be quite variable in the rabbit. a large farm outbreak (kaupke et al., ) had rabbits that presented with lethargy, anorexia and diarrhea. animals showing clinical signs died within - days. the stress of weaning is thought to have exacerbated these signs. another report describes small intestinal dilatation observed during surgery in a rabbit without other clinical signs (inman and takeuchi, ) . epizootiology transmission is likely via ingestion of thick-walled sporulated oocysts. experimentally infected juvenile rabbits began shedding oocysts in their feces - days post infection and continued to shed until days post infection without clinical signs (robinson et al., ) . pathology histopathology of the small intestine of the reported rabbit was characterized by shortened, blunted villi and mild edema of the lamina propria. the lacteals of the ileum were also dilated, and an inflammatory response was observed (inman and takeuchi, ) . diagnosis c. cuniculus is emerging as a potential zoonotic pathogen with several reports in recent years (chalmers et al., (chalmers et al., , zhang et al., ) . in response to this, real-time pcr assays are in development (hadfield and chalmers, ) that detect and differentiate c. cuniculus from c. parvum and c. hominis. differential diagnoses c. cuniculus can only be differentiated from c. hominis and c. parvum via genetic analysis (robinson et al., ) . differential diagnoses would include infection with clostridium piliforme, c. spiroforme, c. difficile, e. coli, lawsonia intracellularis, coronavirus, rotavirus, protozoans, or intestinal parasites. treatment, prevention, and control minimizing stress can possibly prevent or reduce clinical signs laboratory animal medicine (kaupke et al., ) . antibiotics were ineffective in the large farm outbreak. presumably, supportive care (fluids) would be indicated in animals showing clinical signs (schoeb et al., ) . prevention requires husbandry and sanitation practices that prevent exposure. research complications this organism is emerging as a human pathogen, so appropriate precautions should be made to protect research personnel from rabbits positive for c. cuniculus. etiology the etiologic agent responsible for encephalitozoonosis is encephalitozoon cuniculi. this agent is historically known by the name nosema cuniculi (pakes and gerrity, ) and has been divided into three strains (i -rabbit strain, ii -mouse strain, iiidog strain) (didier et al., ) . the disease was first described in as an infectious encephalomyelitis causing motor paralysis in young rabbits (wright and craighead, ) . clinical signs encephalitozoonosis typically has a delayed onset (weeks to months post infection) prior to the exhibition of clinical signs. early infection affects the kidney, liver and lung, while alterations later in the infection are most severe in the kidneys and brain (kunzel and joachim, ) . the organism can be found in the tissues without an inflammatory response (pakes and gerrity, ) . although named for the motor paralysis in young rabbits, the disease is usually latent. if clinical signs are present, they can include convulsions, tremors, torticollis, paresis, and coma (pattison et al., ) as well as signs of kidney failure. intrauterine infection can result in phacoclastic uveitis leading to rupture of the lens capsule (kunzel and joachim, ) . epizootiology transmission is likely horizontal via direct contact or environmental contamination (kunzel and joachim, ) , primarily from ingestion of infected urine (schoeb et al., ; wasson and peper, ) . the pathogen can also be transmitted vertically, as evidenced by in utero pcr positivity reported by baneux and pognan ( ) . pathology the kidneys commonly have lesions at necropsy. typically, there are multiple white, pinpoint areas or gray, indented areas on the renal cortical surface (kraus et al., ) . microscopically, these areas are characterized by granulomatous inflammation. interstitial infiltration of lymphocytes and plasma cells and tubular degeneration may also be present (flatt and jackson, ) . granulomatous encephalitis is a characteristic lesion (fig. . ) (pakes and gerrity, ) . lesions of the spinal cord can also occur (koller, ) . the organisms are often not observed in histologic sections of the lesions. organisms may be seen floating free in the tubules of the kidney (pakes and gerrity, ) . diagnosis diagnosis of encephalitozoonosis can be made using several different methods. histologic examination of tissues and observation of the organism is definitive. brain and kidney samples yield the best detection rates for histopathological diagnosis (leipig et al., ) . the encephalitozoon organism does not stain well with hematoxylin and eosin, and is better demonstrated using giemsa stain, gram stain, or goodpasture's carbol fuchsin stain (pakes, ) . many different serologic tests exist for the organism. indirect fluorescence antibody technique and elisa are both available and reliable (kunzel and joachim, ) . advances in diagnostic techniques have been made in human medicine due to the susceptibility of immunosuppressed patients to this particular infection. several pcr tests for diagnosis and species differentiation of encephalitozoonosis have been developed (croppo et al., ; franzen et al., ; weiss and vossbrinck, ) . pcr can be performed on the intestine, brain, heart, liver, lung, or kidney tissue with a good ( %) overall detection rate reported (leipig et al., ) . differential diagnoses if the animals are demonstrating motor paralysis, conditions such as splay leg should be considered. for neurological signs, consider bacterial meningitis due to p. multocida infection or rabbit hemorrhagic disease. treatment, prevention, and control prevention and control of the organism in the colony are done by elimination of the organism from the colony of infected rabbits. because this is a latent disease in rabbits, serologic methods must be used to identify carriers of the organism. the indirect fluorescence antibody test has laboratory animal medicine been used successfully to identify infected rabbits (cox, ) . the elimination of infected rabbits must be accompanied by disinfection of the environment. several disinfectants have been effective against this organism. encephalitozoon was killed by % (v/v) lysol, % (v/v) formalin, and % (v/v) ethanol (shadduck and polley, ) % hydrogen peroxide, and % sodium hydroxide (kunzel and joachim, ) . successful treatment and prevention of e. cuniculi in the rabbit has been reported with use of fenbendazole (suter et al., ) . for cases of phacoclastic uveitis, removal of the lens is the treatment of choice (kunzel and joachim, ) . research complications encephalitozoonosis is most commonly subclinical disease, which makes it difficult to determine the effects it may have on research. granulomatous reactions would complicate renal physiology and neurologic research. depression of the igg response and an increase in the igm response to brucella abortus antigens has been demonstrated in rabbits infected with encephalitozoon organisms (cox, ) . encephalitozoonosis is also a recognized disease in immunodeficient humans. it is recommended that such individuals seek medical counsel prior to handling rabbits. isolates from humans have been shown to be infectious for rabbits (mathis et al., ) . etiology psoroptes cuniculi is a nonburrowing mite and the causative agent of psoroptic mange, also called ear mange, ear canker, or otoacariasis. the organism is distributed worldwide, but with modern husbandry practices, it is mostly historical in laboratory rabbit colonies (schoeb et al., ) . clinical signs lesions occur primarily in the inner surfaces of the external ear. the lesions are pruritic and can result in scratching, head shaking, pain, and even self-mutilation (hofing and kraus, ) . a tan, crusty exudate accumulates in the ears over the lesions and can become quite extensive and thick (fig. . ) . the skin under the crust is moist and reddened. the ears may become malodorous. epizootiology all stages of the mite (egg, larva, protonymph, and adult) occur on the host. early in the infestation, mites feed on sloughed skin cells and lipids. as local inflammation increases, they ingest serum, hemoglobin, and red blood cells (deloach and wright, ; hofing and kraus, ) . the entire life cycle is complete in days. mites are relatively resistant to drying and temperature and can survive off the host for - days in a temperature range of - °c and relative humidity of - %. pathology lesions are characterized histologically by chronic inflammation, hypertrophy of the malpighian layer, parakeratosis, and epithelial sloughing. a hypersensitivity response to the mites, mite feces, and saliva likely contributes to lesions (hofing and kraus, ) . diagnosis mites are large enough to be seen with the unaided eye or with an otoscope. material scraped from the inner surface of the ear can also be examined using a dissecting microscope. mites are oval-shaped with well-developed legs that project beyond the body margin. adult males measure - μm × - μm, and females measure - μm × - μm (hofing and kraus, ) . differential diagnoses rarely, infection with sarcoptes scabiei or cheyletiella parasitovorax should be considered as differential diagnoses. treatment, prevention, and control several successful treatments have been reported. prior to local treatment, the ears should be cleaned gently to remove accumulated exudate. one treatment involves the application of % rotenone in mineral oil ( : ) every days for days. ivermectin is an effective treatment at dosages of - μg/kg sc or im (curtis et al., ; mckellar et al., ; wright and riner, ) . one or two doses were utilized for effective treatment. treatment of moderate to severe infestations with ivermectin alone can fail. using adjunct vitamin therapy to minimize oxidative tissue damage has been shown to enhance treatment success (singh et al., ) . a single dose of topical selamectin at a minimum of mg/kg selamectin (kurtdede et al., ) and a single injection of laboratory animal medicine eprinomectin at or μg/kg (pan et al., ) were found to be effective treatments. regardless of treatment modality, it is generally recommended that the entire group of rabbits be treated at the same time. heat ( °c) and desiccation (< % humidity) will kill parasites that are not on the host (arlain et al., ) . vaccine targets have been investigated, with gut surface antigen being the primary focus (rossi et al., ) . research complications p. cuniculi has been associated with immune suppression and a systemic inflammatory reaction (shang et al., ) . ear trauma secondary to psoroptes infestation can limit access to the auricular artery and veins. . cheyletiella spp. (c. parasitovorax, c. takahasii, c. ochotonae, c. johnsoni) etiology cheyletiella mites are nonburrowing skin mites of rabbits. they are distributed worldwide. several closely related species have been reported to occur on rabbits, namely, c. parasitovorax, c. takahasii, c. ochotonae, and c. johnsoni (hofing and kraus, ) . clinical signs the anatomic site most commonly infested is the area over the scapulae. there may be mild hair loss in the area, and the skin may have a gray-white scale (cloyd and moorhead, ) . affected rabbits do not scratch, and there is no evidence of pruritus. skin lesions are mild or nonexistent. epizootiology all stages (egg, larva, pupa, and adult) in the life cycle occur on the host. mites remain in association with the keratin layer of the skin and feed on tissue fluid (myktowycz, ) . transmission is probably by direct contact (schoeb et al., ) . pathology when present, skin lesions are characterized by mild dermatitis, hyperkeratosis, and an inflammatory cell infiltrate (hofing and kraus, ) . diagnosis mites can be isolated by scraping or brushing fur in the affected areas onto a slide. clearing samples with - % potassium hydroxide will improve visibility of the mites, which can then be identified using a dissecting microscope. the female measures × μm, and the male is × μm. cheyletiella mites have a large, distinctive curved claw on the palpi (pegg, ) . differential diagnoses other skin mites (such as sarcoptes scabei) or fur mites (leporacarus gibbus) that can affect rabbits should be considered as well as the possibility of dermatophytosis. treatment, prevention, and control topical acaricides are often used and are effective at controlling infestation. ivermectin (subcutaneous or subcutaneous and oral) and selamectin (topical) treatments have been used successfully. eggs in the environment can reinfest the host, so posttreatment environmental sanitation is important (mellgren and bergvall, ) . research complications cheyletid mites can cause a transient dermatitis in humans who are in close contact with infested animals (cohen, ; lee, ) . for this reason, these mites can be considered a zoonotic pathogen. etiology sarcoptes scabiei is a burrowing mite and the causative agent of sarcoptic mange. mites of the genus sarcoptes are generally considered to be one species, s. scabiei, but are often further identified by a variety name corresponding to the host species (e.g., s. scabiei var. cuniculi). the organisms are commonly referred to as itch or scab mites. the disease has a worldwide distribution. clinical signs affected rabbits will exhibit intense pruritus with hair loss and abrasions as a resulting from scratching. serous encrustations on the skin and secondary bacterial infections are common. there has been one report of a secondary infection with the yeast malassezia (radi, ) . anemia and leukopenia can also be observed in affected rabbits (arlain et al., ) . epizootiology sarcoptic are similar to notoedric mites (notoedres cati) in morphology, life cycle, and public health significance. mites burrow and produce an intensely pruritic dermatitis. lesions are most common on the head (hofing and kraus, ) . all stages of sarcoptic mange mites occur on the host. the females burrow into the skin to lay eggs. young larvae can also be found in the skin, whereas older larvae, nymphs, and males reside on the skin surface. mites feed on lymph and epithelial cells (hofing and kraus, ) . pathology amyloidosis of the liver and glomerulus have been reported in rabbits with severe infestation (arlain et al., ) . the skin itself is hyperplastic and hyperkeratotic, with inflammatory response evident in the dermis (schoeb et al., ) . diagnosis because sarcoptes is a burrowing mite, skin scrapings are necessary to diagnose infestation. samples may be cleared with - % potassium hydroxide. female mites measure - μm × - μm. the body shape is round, and the legs are very short. differential diagnoses other causes of dermatitis in rabbits (such as cheyletiella spp., p. cuniculi or dermatophytosis) should be considered. ivermectin is effective at eliminating infestation at μg/kg administered subcutaneously. a single topical dose of selamectin at - mg/kg reduced the number of mites found on skin scrapings of angora rabbits (kurtdede et al., ) and eliminated clinical signs and parasitic infestation in a group of mixed-breed rabbits at a dose of mg/rabbit (farmaki et al., ) . as with psoroptes, more 'natural' treatments are being investigated with good preliminary results from eugenol (pasay et al., ) and eupatorium spp. (nong et al., ) . research complications no specific research complications have been reported. sarcoptes can cause a selflimiting dermatitis in humans. a wide variety of arthropod parasites has been reported in wild rabbits but they are extremely rare in laboratory rabbits. for an extensive listing the reader is referred to other sources (hofing and kraus, ) . etiology historically, the rabbit pinworm was identified as oxyuris ambigua, but is now known as passalurus ambiguus (hofing and kraus, ) . clinical signs even when rabbits have heavy oxyurid burdens, clinical signs are not usually apparent (erikson, ; soulsby, ). one case report described unsatisfactory breeding performance and poor condition in a rabbit colony infested with the parasite. epizootiology p. ambiguus has a direct life cycle. mature pinworms are found in the lumen of the cecum or colon of the rabbit. after ingestion, the eggs hatch in the small intestine, and the larvae molt with maturation in the cecum. the prepatent period is between and days (taffs, ) . transmission occurs easily via ingestion, given that individual rabbits have been found with over adult parasites (hofing and kraus, ) and that embryonated eggs pass out in the feces and are immediately infective (schoeb et al., ; taffs, ) . pathology minimal to no lesions are associated with this pinworm (schoeb et al., ) . diagnosis eggs can be found in feces, cecum, or colon. differential diagnoses this is the only reported pinworm in rabbits and it is not known to cause lesions or disease. treatment, prevention, and control several successful treatment strategies for rabbit oxyuriasis have been reported. piperazine citrate at mg/ ml of drinking water for day was successful in eliminating infestation (hofing and kraus, ) . at and ppm, fenbendazole mixed in the food for days eliminated all immature and adult pinworms (duwell and brech, ) . subcutaneous doses of ivermectin ( . mg/kg) were reported to be ineffective in reducing the burden of passalurus organisms in field populations of snowshoe hares (lepus americanus) (sovell and holmes, ) . due to the direct life cycle, strict husbandry and sanitation practices are required to prevent introduction and spread throughout a rabbit colony (schoeb et al., ) . research complications none have been described. etiology dermatophytosis, also known as ' ringworm' or 'tinea', refers to a skin infection caused by a dermatophyte, a keratinophilic and keratinolytic fungus (chermette et al., ; mendez-tovar, ; robert and pihet, ) . dermatophytes are a group of closely related filamentous fungi that are able to invade the stratum corneum of the epidermis and keratinized tissues including the skin, nail, and hair (kanbe, ) . dermatophytes can infect various animal species, including humans, and the disease is considered contagious and zoonotic (cafarchia et al., b; chermette et al., ; kramer et al., ) . the zoophilic dermatophytes trichophyton mentagrophytes and microsporum canis infect rabbits (cafarchia et al., (cafarchia et al., , a chermette et al., ; kramer et al., ) . clinical signs the general presentation of dermatophytosis in animals is an area of circular alopecia with erythematous margin and thin desquamation (chermette et al., ) . pruritus is generally absent and lesions can be single or multiple (chermette et al., ) . although lesions can be localized in any region, the anterior part of the body and the head seem to be more frequently involved (chermette et al., ) . in rabbits, lesions are often found on the ears and the face (around the eyes and on the nose) and these lesions show scaling and crusting (chermette et al., ; kramer et al., ) . infected rabbits may not exhibit clinical signs and may serve as carriers (balsari et al., ; cafarchia et al., cafarchia et al., , a chermette et al., ; lopez-martinez et al., ) . epizootiology although dermatophytosis is a common cutaneous disease of rabbits and other animals, its incidence is low in well-managed laboratory animal facilities (chermette et al., ; connole et al., ) . contact with infected animals or contaminated environments represent the major risk of infection (chermette et al., ) . young or immunocompromised rabbits are more susceptible (connole et al., ; kramer et al., ) . on rabbit farms, the occurrence of lesions, the age of the rabbits, and farm management practices were identified as the most significant risk factors for the occurrence of dermatophytosis (cafarchia et al., ) . clinically, disease expression varies depending on the host, fungal species, and enzyme production (cafarchia et al., a; vermout et al., ) . the pathogenesis involves contact, adherence, germination, invasion, and penetration (cafarchia et al., a; mendez-tovar, ; vermout et al., ) . these stages can be associated with the secretion of enzymes that degrade the infected tissue components (cafarchia et al., a) . t. mentagrophytes isolates from rabbits with skin lesions showed a significantly higher elastase and gelatinase activity compared laboratory animal medicine to isolates from clinically unaffected rabbits and from the environment (cafarchia et al., a) . furthermore, m. canis isolates from rabbits with skin lesions showed a significantly higher lipase activity compared to isolates from clinically unaffected rabbits and from the environment (cafarchia et al., a) . pathology histopathologic changes consist of mild to severe dermatitis. diagnosis the wood's lamp (ultraviolet light) method and direct examination of hairs and scales are fast and affordable tests (chermette et al., ; robert and pihet, ) . the wood's lamp can be used to screen for infections caused by m. canis (chermette et al., ) . m. canis-infected hairs fluoresce with an apple-green color and can be collected for microscopic examination and culture (chermette et al., ) . the results of the wood's lamp examination should be systematically confirmed by direct examination of hairs and/or fungal culture (chermette et al., ) . deep skin scraping should be performed to obtain hair and scales and confirm the absence of ectoparasites such as mites that can be associated with dermatophytosis (cafarchia et al., ; chermette et al., ) . clearing solutions such as chlorolactophenol or % potassium hydroxide (koh) can then be used to digest keratin prior to microscopic examination (chermette et al., ; robert and pihet, ) . the surface of the hair typically demonstrates clusters or chains of arthroconidia (chermette et al., ) . giemsa-stained skin scrapings allow observation of the arthroconidia along the hair (chermette et al., ) . fungal culture is the 'gold standard' for the diagnosis of dermatophytosis and the only method for the phenotypic identification of dermatophyte species (chermette et al., ) . the fungal culture must be complemented with direct examination of samples for optimal interpretation of the results (chermette et al., ; robert and pihet, ) . samples for fungal culture may include hairs, scales, crusts, skin scrapes, and tissue biopsies (chermette et al., ) . samples that are obtained from the margin of new skin lesions enhance fungal recovery by culture (chermette et al., ) . a brush can also be impressed on the surface of the culture medium after combing the fur and obtaining fungal spores with hair and debris (robert and pihet, ) . two media that can be used for fungal culture include sabouraud dextrose agar (supplemented with cycloheximide and antibiotics) and dermatophyte test media (dtm) (chermette et al., ; robert and pihet, ) . if histological examination is performed, periodic acid schiff (pas), or methylamine silver stain can be used to detect arthroconidia and hyphae (chermette et al., ) . molecular methods to identify dermatophytes have also been described and include pcr-rflp and sequencing of the internal transcribed spacer (its) region (chermette et al., ; kanbe, ; robert and pihet, ) . specific identification of the dermatophyte is essential for a better understanding of the epidemiology and prevention of the disease (chermette et al., ) . differential diagnoses the differential diagnoses can include other dermatoses caused by bacteria or ectoparasites (cafarchia et al., ; chermette et al., ) . treatment, prevention, and control dermatophytosis is considered a self-limiting disease in immunocompetent animals (chermette et al., ) . however, rabbits with dermatophytosis should be culled or separated from a laboratory animal colony due to the contagious and zoonotic nature of the disease (chermette et al., ) . the best method to prevent dermatophyte infection is to prevent contact with infected animals and contaminated environments including fomites (chermette et al., ) . an animal that contacts an infected animal or a contaminated environment can be washed with antifungal shampoo (chermette et al., ) . two vaccines incorporating live attenuated cells of t. mentagrophytes have been used to prevent disease in rabbits and other animals (lund and deboer, ) . the mentavak vaccine is from russia and the trichopelen vaccine (http://www. bioveta.cz/en/veterinary-division/home/) is from the czech republic (lund and deboer, ) . trichopelen is also indicated for treatment of dermatophytosis (lund and deboer, ) . enzootic dermatophytosis may be the result of the high resistance of the arthroconidia in the environment, the number of host species involved, and the close confinement of animals (chermette et al., ) . isolation or culling of infected animals plus environmental and equipment disinfection are required to control this disease (chermette et al., ) . a : dilution of household bleach or a . % enilconazole solution can be used to disinfect the environment (chermette et al., ) . infected animals should be handled with care to avoid zoonotic transmission (chermette et al., ) . if treatment is elected, antifungal treatment shortens the course of the infection and reduces dissemination of arthroconidia to other animals and into the environment (chermette et al., ) . systemic and topical antifungal treatment can be used in combination (chermette et al., ) . systemic drugs include griseofulvin (gold standard) or azole derivatives such as itraconazole (chermette et al., ; vella, ) . it is important to know that these drugs can have side effects and be contraindicated due to their teratogenic potential (chermette et al., ) . topical treatment may include . % enilconazole, a combination of % miconazole and % chlorhexidine, or lime sulfur (chermette et al., ; vella, ) . treatment can be discontinued after two negative fungal culture results (chermette et al., ) . research complications dematophyte lesions could confound histological studies involving the skin (connole et al., ) . etiology pneumocystosis in rabbits is caused by the fungus pneumocystis oryctolagi (dei-cas et al., ) . clinical signs infected rabbits may not develop clinical signs, but immunocompromised hosts can develop severe interstitial pneumonitis (dei-cas et al., ; sheldon, ) . epizootiology corticosteroid treatment can induce disease in infected rabbits; however, spontaneous disease (not associated with drug treatment) can also occur (dei-cas et al., ; sheldon, ; soulez et al., ) . p. oryctolagi is transmitted through the transplacental route (cere et al., a; sanchez et al., ) and through direct contact and aerosolization (cere and polack, ; cere et al., b; hughes, ; wakefield, wakefield, , . spontaneous pneumocystosis can occur at weaning, evolves during - days, and induces lung lesions and blood biochemical profile changes (dei-cas et al., ; soulez et al., ) . the organisms attach specifically to type epithelial alveolar cells and proliferate, filling up pulmonary alveoli cavities leading to respiratory failure (dei-cas et al., ) . changes in surfactant appear to be necessary for pneumocystis proliferation (prevost et al., ) . pneumocystis colonization decreases and becomes very low in -day-old rabbits (dei-cas et al., ) . most rabbits recover from pneumocystosis within - weeks (dei-cas et al., ) . the spontaneous resolution of pneumocystosis in rabbits may be associated with expression of interferon gamma (allaert et al., ) . immunosuppression may be suspected in cases of severe pulmonary disease associated with spontaneous pneumocystosis (sheldon, ) . pathology histologically, cystic forms of the organism can be detected in the lungs using toluidine blue o (tbo), gms, or pas stains (dei-cas et al., ) . interstitial thickening of alveolar septa and increased numbers of type epithelial alveolar cells are characteristic of this infection (creusy et al., ) . diagnosis for diagnosis, samples from nasal cavity wash, or post-mortem, from terminal bronchoalveolar lavage (bal) or lung homogenates can be used for pneumocystis detection by nested pcr (dei-cas et al., ; tamburrini et al., ; wakefield, ) . serological diagnosis can also be performed (tamburrini et al., ) . lung impression smears, lung-homogenate smears, and bal fluid samples can be stained for microscopic detection of pneumocystis (dei-cas et al., ) . useful stains include tbo, gomori-grocott's methenamine silver nitrate (gms), and methanol-giemsa or giemsalike stains (dei-cas et al., ) . other useful detection methods include phase-contrast microscopy and the use of pneumocystis-specific fluorescein-labeled antibodies (dei-cas et al., ) . differential diagnoses p. multocida can induce respiratory disease in rabbits and can be included in the differential diagnoses. treatment, prevention, and control for prevention, new rabbits should be negative for pneumocystis. cotrimoxazole treatment and nested pcr have been used as a screening mechanism to eliminate pneumocystis from colony-maintained rabbits (cere et al., c) . decontamination practices and air filtration were also important for eradication (cere et al., c) . confirmation of a pneumocystis-free status in a rabbit colony was demonstrated by negative pcr results and/ or failure to induce pneumocystosis after experimental corticosteroid challenge (dei-cas et al., ) . research complications research studies may be affected if rabbits of unknown pneumocystis status are experimentally treated with corticosteroids or other immunosuppressant drugs (sheldon, ) . pulmonary lesions may be found in infected rabbits and could potentially confound respiratory research studies (sheldon, ) . etiology unknown. clinical signs trichobezoar is often subclinical. if the trichobezoar causes partial or complete blockage, clinical signs of gastric or intestinal obstruction will result. death can occur due to prolonged anorexia and metabolic imbalances (gillett et al., ). it appears that obstruction of the pylorus, and not the volume of the gastric mass, is the critical factor in determining the clinical progress of the animal (leary et al., ) . epizootiology the condition occurs sporadically in rabbit colonies. pathology the discovery of a hairball in a rabbit is often an incidental finding during necropsy. up to % of rabbits have been found to have gastric trichobezoars during routine necropsy (leary et al., ) . gastric rupture can also result from an obstructive trichobezoar (gillett et al., ) . diagnosis diagnosis is often difficult because the clinical signs are nonspecific and the disease often progresses gradually. some cases involving acute pyloric obstruction result in sudden clinical disease and rapid clinical decline of the animal. manual palpation may indicate the presence of a firm mass in the cranial abdomen. gastric radiographs using contrast media may aid in the diagnosis, but definitive diagnosis is often made during exploratory surgery (gillett et al., ) . differential diagnoses constipation and intestinal foreign body should be considered in the differential list. treatment, prevention, and control treatment of trichobezoar is often unsuccessful. oral administration of mineral oil at ml/day has been reported (suckow and douglas, ) . alternatively, oral administration of - ml of fresh pineapple juice daily has been reported as a possible treatment modality (harkness and wagner, ) . if medical treatment does not resolve the condition, a gastrotomy should be performed. early surgical intervention is important in such cases, as other, subsequent metabolic abnormalities may quickly increase the surgical risk to the rabbit (bergdall and dysko, ) . research complications none have been reported. etiology subluxation or compression fractures of lumbar vertebrae are often secondary to struggling during restraint, particularly when the hindquarters of the rabbit are not supported (bergdall and dysko, ) . the seventh lumbar vertebra (l ) or its caudal articular processes are considered the most frequent sites of fractures, with fracture occurring more commonly than dislocation (flatt et al., ) . clinical signs clinical signs include posterior paresis or paralysis, loss of sensation in the hindlimbs, urinary and/or fecal incontinence, and perineal staining. pathology spinal cord hemorrhage and necrosis can be found. diagnosis diagnosis is based on clinical signs, history of recent restraint, struggling or other trauma, and palpation or radiographic analysis of the vertebral column. differential diagnoses spinal cord trauma. treatment, prevention, and control euthanasia of affected animals is usually warranted. moderate cases (subluxation with spinal edema) may resolve over time. the decision to euthanize should be based on severity of clinical signs. supportive care includes regular expression of the urinary bladder and prevention and treatment of decubital ulcers. corticosteroid and diuretic therapy may be effective for cases of subluxation with spinal edema (bergdall and dysko, ) . research complications loss of valuable research animals is the primary complication. although the condition is often referred to as 'sore hocks,' the correct name is ulcerative pododermatitis. despite the name, the condition rarely affects the hocks, but rather occurs most frequently on the plantar surface of the metatarsal and, to a lesser extent, the metacarpal regions. the condition is believed to be initiated by wire-floor housing, foot stomping, or having thin plantar fur pads. poor sanitation may worsen the condition. solid resting areas on the cage floors are associated with a decreased incidence of ulcerative pododermatitis, whereas a high-energy diet and increased body condition scores are associated with an increased incidence (sanchez et al., ) . the whole genome sequence from a single female rabbit of the partially inbred thorbecke rabbit strain was published in (orycun . ; accession aagw ). the annotated assembly is now available at the national center for biotechnology information (ncbi), the university of california santa cruz (ucsc), and ensembl. the rabbit chosen by the broad institute for sequencing was obtained from covance in . the assembly has . gbp in autosome and x chromosomes and mbp in unplaced scaffolds including mitochondria (gertz et al., ) . the nucleotide sequence of the complete mitochondrial dna (mtdna) molecule of the o. cuniculus has been determined (gissi et al., ) . the compositional differences between the two mtdna strands have also been detailed (gissi et al., ) . the sequencing of the rabbit genome, understanding of rabbit reproduction, and advances in genetic manipulation in the mouse production colonies have led to the ability to produce genetically engineered rabbits. the rabbit offers an alternative model when size or tissue characteristics of a genetically modified mouse are not appropriate. these genetic manipulation techniques were first described by robl (robl and burnside, ) . additional methods have been developed and include pronuclear injection of single cell embryos, injection of genetically modified embryonic stem cells into blastocysts, sperm-mediated gene transfer, and genetically modified somatic cell and nuclear transfer (christensen and peng, ) . commercial companies have been formed to provide genetic modification services with emphasis on production of a unique protein in the milk of rabbits. this section will outline spontaneous hereditary conditions of the rabbit that have been well characterized. some conditions represent conditions that have been identified in humans and other conditions offer insight into the mechanism(s) of particular organ or immune function. hydrocephalus refers to dilatation of the cerebral ventricles and is usually accompanied by accumulation of cerebrospinal fluid within the dilated spaces. some cases of hydrocephalus in rabbits have been presumed to be related to a single autosomal recessive gene (hy/hy); however, occurrence with other abnormalities suggests that inheritance may be more complicated (lindsey and fox, ) . in some cases, the condition appears to be inherited along with various ocular anomalies as an autosomal gene with incomplete dominance. hydrocephalus may also occur in rabbits as a congenital condition related to hypovitaminosis a in pregnant does (lindsey and fox, ) . etiology buphthalmia is inherited as an autosomal recessive trait, although penetrance is presumably incomplete since severity and the age of onset vary greatly and some bu/bu individuals do not develop buphthalmia (hanna et al., ) . clinical signs rabbits with hereditary glaucoma develop ocular changes that resemble human congenital glaucoma and buphthalmia. newborn bu/bu rabbits initially have normal intraocular pressure (iop; - mmhg) but increased pressures of - mmhg may develop after - months of age (burrows et al., ; knepper et al., ) . the eyes become progressively buphthalmic (either uni-or bilaterally) but the iop can return to normal or to sub-normal levels after - months. typical clinical changes include increased corneal diameter as the globe enlarges because the sclera is still immature. the cornea may develop a cloudy or bluish tint, corneal edema, increased corneal vascularity, and flattening of the cornea. structural changes may include widening of the angle, thickening of descmet's membrane, atrophy of the ciliary process, and excavation of the optic disk. impaired aqueous outflow may be due to incomplete cleavage of the drainage angle with abnormal insertion of uveal tissue into the cornea (tesluk et al., ) . in some cases, the cornea ulcerates and ruptures. there is also a marked reduction in semen concentration in buphthalmics, with a decrease in libido and decreased spermatogenesis in affected males (fox et al., ) . epizootiology the condition is common in new zealand white rabbits. pathology by weeks of age, the morphology of the congenital glaucoma trabecular network becomes abnormal with a smaller entrance to the trabecular network at the iris base, smaller intertrabecular openings within and between the trabecular lamellae, and by weeks, iris pillars with extensive lateral extensions in the angle recess can be observed. most intertrabecular spaces remain open; however, the inner intertrabecular spaces adjacent to the aqueous plexus become compressed. diagnosis diagnosis is based on clinical signs and measurement of intraocular pressure. treatment, prevention, and control specific treatment of buphthalmia has not been described for rabbits; however, affected individuals should not be used for breeding purposes. research complications loss of valuable research animals is the primary complication. etiology mandibular prognathism is the most common inherited disease of domestic rabbits. the condition is inherited as an autosomal recessive trait (mp/mp) with incomplete penetrance (fox and crary, ; huang et al., ; lindsey and fox, ) . clinical signs malocclusion related to mandibular prognathia may be clinically apparent as early as - weeks of age, but is more typically seen in older rabbits post weaning. clinical signs may include anorexia and weight loss. if severe enough and left untreated, affected animals will starve since they cannot properly prehend and masticate food. epizootiology normally, the lower incisors occlude with the large upper incisors, as well as with a pair of small secondary incisors that are immediately caudal to the primary maxillary incisors. the lower set of incisors typically wear against the upper set during normal biting activity, along an arc formed by biting movements of the lower incisors, whereas the maxillary secondary incisors wear at right angles to the mandibular incisors. the incisors wear more quickly at the posterior aspect in rabbits, partly because the enamel layer is thinner on that side. affected rabbits have a normal dental formula. the specific abnormality associated with mandibular prognathism is that the maxilla is short relative to a mandible of normal length. thus, although the mandible appears abnormally long, the primary defect involves the maxilla. in rabbits, the teeth (including the molars and premolars) grow continuously throughout life. the incisors, for example, grow at the rate of . - . mm/ week. when occlusion is normal, the teeth wear against one another and in this way remain a normal length. however, when occlusion is abnormal because of conditions that include mandibular prognathia, the teeth may become greatly elongated because typical attrition of the incisors does not occur. in affected animals the lower incisors often extend anterior to the upper incisors and protrude from the mouth, whereas the upper primary incisors grow past the lower incisors and curl within the mouth. in some instances, the upper incisors curl around dorsally and lacerate the mucosa of the hard palate. secondary infection and abscessation may occur in such cases. diagnosis diagnosis is based on clinical signs. differential diagnoses malocclusion secondary to mandibular or maxillary fracture should be considered. treatment, prevention, and control overgrown teeth should be trimmed every - weeks or more frequently if needed. trimming is preferably performed with a dental bur to avoid cracking the tooth, which laboratory animal medicine may happen more frequently if a bone or wire cutter is used. care should be taken to avoid exposing the pulp cavity as the result of excessive trimming. because the condition is hereditary, use of affected animals as breeding stock should be avoided. research complications no specific research complications have been reported. a number of disorders characterized clinically by complete abduction of one or more legs and the inability to assume a normal standing position are described by the term 'splay leg'. young kits of - weeks of age are most commonly affected. affected rabbits cannot adduct limbs and have difficulty in making normal locomotory movements. most commonly, animals are affected in the right rear limb, although the condition may be uni-or bilateral and may affect the anterior, posterior, or all four limbs. rabbits with splay leg may have difficulty in accessing food and water; thus, attention to adequate nutrition is required as part of proper clinical care. the clinical signs of splay leg may be due to an overall imbalance of development of the neural, muscular, and skeletal systems. possibly, some animals compensate with torsion and exorotation of the limb at the hip, whereas rabbits that are unable to compensate are clinically affected. although the precise pathogenesis of splay leg is not entirely understood, at least some cases are ascribed to inherited disorders. typical clinical signs are secondary to femoral endotorsion, with a shallow acetabulum but without luxation of the femur at the hip. the semitendinosus muscle of affected animals is abnormal, with smaller fibers and abnormal mitochondria. some reports suggest that the condition is associated with inherited achondroplasia of the hip and shoulder, whereas others indicate that a recessively inherited anteversion of the femoral head can be involved. self-mutilating behavior in a checkered cross (cross between english spot, german checkered giant, and checkered of rhineland rabbits) was reported to occur as an inherited trait (iglauer et al., ) . autotraumatization of the feet and pads was observed. the abnormal behavior could be interrupted by administration of haloperidol. although not manifested as a disease, the presence of serum atropine esterase allows rabbits to inactivate atropine when administered for therapeutic purposes (liebenberg and linn, ; stormont and suzuki, ) . the enzyme also permits rabbits to consume diets containing belladonna compounds. the enzyme is produced by a semidominant gene est- f. three phenotypes are recognized depending on the number of genes expressed. the enzyme first appears in the serum at month of age, and enzyme levels are greater in females than in males (lindsey and fox, ) . the est- f gene is linked to genes controlling the black pigment in the coat (forster and hannafin, ; fox and van zutphen, ; sawin and crary, ) . hereditary deficiency of the third component of complement (c ) was found in a strain of rabbits. this same strain also exhibited a hereditary c alpha-gamma deficiency. the serum c concentration, hemolytic c activity, and total complement hemolytic activity of these animals were significantly reduced. the low level of serum c in these rabbits was not due to c conversion, partial c antigenicity, and presence of a c inhibitor or hypercatabolism of normal c . the c deficiency was transmitted as a simple autosomal co-dominant trait. rabbits with this trait have a lower survival at months than normal rabbits (komatsu et al., ) . this complement deficiency syndrome in the rabbit has been well characterized. this syndrome was initially reported in in a strain of rabbits that lacked the sixth component of the hemolytic complement system (rother et al., ) . whole blood clotting time in glass or plastic was prolonged and prothrombin consumption was decreased in blood from the deficient animals. other parameters of blood coagulation were normal, including prothrombin time, partial thromboplastin time, specific clotting factor activities, platelet factor iii function, platelet count, and bleeding time (zimmerman et al., ) . abnormal platelet response is also characteristic of this syndrome in the rabbit (lee et al., ) . complement c -deficient rabbits are protected against diet-induced atherosclerosis despite having similar profiles in cholesterol levels and plasma lipoprotein. when compared to normal rabbits, differences in atherosclerotic plaque formation were discernible macroscopically, with extensive aortic lesions being visible in all normal rabbits while absent in all c -deficient animals (schmiedt et al., ) . the inheritance pattern for this defect is autosomal recessive (abe et al., ) . a progressive neurological syndrome has also been observed in the c -deficient rabbits. this syndrome is clinically characterized by subacute motor neuropathy. pathological studies of affected animals revealed ( ) severe axonal degeneration in the sciatic nerve involving mainly motor fibers; ( ) occasional peripheral axonal enlargement closely associated with axonal laboratory animal medicine degeneration; ( ) presence of structured abnormal material in normal-size myelinated fibers of the central and peripheral nervous systems; and ( ) widespread occurrence of dystrophic axons and axonal spheroids in the gray matter of the central nervous system. by ultrastructural examination, dystrophic axons were filled with tubulovesicular material, appearing as stalks of parallel membranes and dense bodies similar to what is described in human neuroaxonal dystrophies (nad). the disease manifested by c -deficient rabbits may represent an animal model of primary human nad (giannini et al., ) . genetic deficiency of the alpha-gamma-subunit of the eighth complement component (c alpha-gamma) was found in a substrain of the new zealand white rabbits. the serum of this deficient rabbit lacked the immunochemical and functional alpha-gamma-subunit of c (c d). this syndrome is transmitted as a simple autosomal recessive trait. the syndrome is characterized by smaller body weight compared to those of heterozygous and normal rabbits. in addition, survival rates for the first months of life of the deficient animals tended to be lower than those of heterozygous and normal littermates (komatsu et al., ) . all c d rabbits (more than animals obtained thus far) were consistently smaller than normal littermates from birth to adulthood, i.e., % of normal size at birth, % of normal size at days of age, and % of normal size at adulthood. the c α-γ deficiency in rabbits is always associated with dwarfism. furthermore, there appears to be a discrete recessive dwarf gene (dw- ), whose locus is not linked to c d. rabbits double-homozygous for c d and dw- (severe dwarf) were smaller than the c d or dwarf rabbits and almost all of the severe dwarf rabbits died within days after birth. the actual and relative weights of the thymus in the c d rabbits were consistently lower than those of normal rabbits, but histological examination of the c d thymus did not reveal any abnormalities. the c d and dwarf rabbits were fertile; however, crosses of c d females with c d or dwarf males led to a reduced delivery rate and small litter size. the c d locus is loosely linked to the c hypocomplementemic locus (c -hypo) (map distance cm) but not to the hemoglobin blood group locus (komatsu et al., ) . the inherited characteristics of the kurosawa and kusanagi hypercholesterolemic (khc) rabbit include persistent hypercholesterolemia. this strain of rabbits was produced by inbreeding mutants discovered in . these khc rabbits had serum cholesterol, triglyceride, and phospholipid levels - times greater than clinically normal o. cuniculus. the khc rabbits also had decreased serum high-density lipoprotein cholesterol concentration, about one-third the value in clinically normal rabbits. in addition, the serum lipoprotein electrophoretic patterns were characterized by a strong, broad beta-lipoprotein band and a diminished alphalipoprotein band. fractionation of lipoprotein lipids revealed increased cholesterol, phospholipid, and triglyceride in the ldl fraction; increased cholesterol and phospholipid in the very ldl fraction; and decreased cholesterol and triglyceride in the high-density lipoprotein fraction. the inheritance is thought to be a single autosomal recessive gene mutation, and analysis of the ldl receptor indicated that the khc rabbit has a -base pair deletion in the ldl receptor mrna. macroscopic analysis of the aorta revealed the atheromatous lesions at months of age, drastically increased lesional areas in the total aortic surface at months of age, and a high incidence of coronary atheromas and xanthomas (kurosawa et al., ) . a spontaneous phenotype in a rabbit was discovered with an elevation of serous lipid ingredients including cholesterol and beta-lipoprotein (beta-lp). atherosclerotic lesions were evident in the aorta and renal arteries. nodular xanthomas were also present on the front and rear feet. the hlr strain was inbred to accentuate these characteristics (watanabe et al., ) . the strain was eventually designated the watanabe-heritable hyperlipidemic rabbit (whhl-rabbit). an additional report of this strain of rabbits indicated that the whhl-rabbits spontaneous developed aortic atherosclerosis by months of age and xanthoma of digital joints in % of the rabbits aged to months (watanabe, ) . historically, spontaneous neoplasia in the laboratory rabbit has not been widely reported because neoplasia in the rabbit is very uncommon before years of age and many laboratory rabbits are not maintained beyond this age (weisbroth, ) . endometrial adenocarcinoma is the most common tumor in aged female rabbits, with an incidence of % reported in a colony of -year-old rabbits (baba and von haam, ) . tinkey et al. complied an extensive review of the literature dealing with spontaneous neoplasia in the domestic rabbit. this review contained data on case reports, descriptions of biologic aspects of naturally occurring tumors and reports of experimentally induced tumor models. neoplasia in sylvilagus and lepus were also discussed (tinkey et al., ) . uterine adenocarcinoma is by far the most common tumor in rabbits. typically, the disease is present as multiple tumors and is malignant, often metastasizing to the liver, lungs, and other organs. there is evidence that inheritance plays a role in susceptibility, but parity does not. uterine leiomyomas and leiomyosarcomas are much less common (weisbroth, ) . there are a few reports of vaginal squamous cell carcinomas (weisbroth, ) and an ovarian hemangioma has been described (greene and strauss, ) . mammary adenocarcinomas are fairly common in older female rabbits and may occur in animals with uterine adenocarcinoma (weisbroth, ) . papillomas have been described, but mammary adenocarcinomas are much more important. these malignant tumors may metastasize, but the cause of death in affected rabbits is often due to uterine adenocarcinoma. serial biopsy studies indicate that these tumors are preceded by cystic mastopathy as well as changes in the adrenal and pituitary glands (greene, ) . there may also be small prolactin-secreting pituitary adenomas in rabbits with mammary dysplasia (lipman et al., ) . testicular tumors in the rabbit appear to be relatively uncommon. interstitial tumors are the most common testicular tumor in the rabbit. seminomas and teratomas have also been reported (weisbroth, ) . embryonal nephromas are one of the most common tumors in laboratory rabbits. these tumors are often found incidentally, occur in younger animals, and seldom cause clinical signs (weisbroth, ) . there has been one report of a renal carcinoma in the rabbit (kaufman and quist, ) and one report of a leiomyoma arising in the urinary bladder (weisbroth, ) . malignant lymphomas (lymphosarcomas) are relatively common in rabbits. they may occur in rabbits that are less than years of age (weisbroth, ) , but older rabbits may also be affected. according to (weisbroth, ) , a tetrad of lesions is often seen. these lesions include enlarged kidneys, splenomegaly, hepatomegaly, and lymphadenopathy. older rabbits have presented with skin nodules and eye lesions; however, malignant lymphomas in the rabbit are seldom leukemic. most cases of malignant lymphoma appear to resemble the lymphoblastic subtype as seen in humans and mice. malignant lymphoma is more prevalent in some strains of rabbits than in others, and there is some evidence for a retroviral cause of lymphomas in rabbits (weisbroth, ) . true thymomas (containing both lymphoid and epithelial components) (vernau et al., ) and plasma cell myelomas (pascal, ) are rare in rabbits. one case of myeloid leukemia has been reported (meier et al., ) . basal cell tumors are reported to be rare (weisbroth, ) , but they may be underreported (li and schlafer, ) . squamous cell carcinomas are also uncommon, and there is no apparent predilection for any particular area of the body (weisbroth, ) . other cited skin-associated tumors include a trichoepithelioma (altman et al., ) , a sebaceous gland carcinoma (port and sidor, ) , and two malignant melanomas (hotchkiss et al., ) . osteosarcomas are extremely rare in rabbits, and most have arisen in the mandible or maxilla, with only one found in a long bone (weisbroth, ) . no primary tumors arising in cartilage have been described, although some of the reported osteosarcomas have had cartilaginous elements. one tumor of skeletal muscle, a rhabdomyosarcoma, has been reported. a few fibrosarcomas and one fibrosarcoma involving the foot have been reported (weisbroth, ) . a number of case reports of single tumors are found in the literature. these include a peritoneal mesothelioma (lichtensteiger and leathers, ) , an intracranial teratoma (bishop, ) , an ependymoma (kinkier and jepsen, ) , a neurofibrosarcoma, two hemangiosarcomas (pletcher and murphy, ) , and a malignant fibrous histiocytoma (yamamoto and fujishiro, ). there are a few very old reports of lung tumors dating to the first part of the th century (weisbroth, ) . there are several tumor models in which the cells used for inoculation were originally derived from rabbit tumors. these include the vx- carcinoma (kidd and rous, ) , the brown pearce carcinoma (brown and pearce, ) , and the greene melanoma (greene, ) . the vx- carcinoma originated from a squamous cell carcinoma in a rabbit carrying a shope papilloma. the most common modern use of this transplantable tumor is as a model for the study of various cancer treatment modalities for metastatic tumors (stetson et al., ) . the brown pearce carcinoma arose from a tumor in a rabbit testis, but the exact tissue of origin of the tumor was never determined. the tumor was readily transplantable and caused stable metastases. because some tumors regress, even after widespread metastases, this tumor has been used as a model for the study of tumor immunology (weisbroth, ) . the brown pearce laboratory animal medicine carcinoma, although extensively characterized and historically used, has been reported in the literature only five times from to (tinkey et al., ) . hydrometra has been described as a clinical condition of rabbits. all cases were in unmated rabbits that were used experimentally for the production of serum antibodies (bray et al., ; hobbs and parker, ; morrell, ) . clinical signs included abdominal distension and tachypnea. cases were characterized by distension of the uterine horns with a transudative fluid. one case was associated with uterine torsion (hobbs and parker, ) . one case had resolved with diuretic therapy, only to return later (bray et al., ) . most cases of liver lobe torsion in rabbits involve the caudate lobe (bergdall and dysko, ) , although one case report described torsion of the left hepatic lobe (wilson et al., ) . most reported cases have been incidental findings at necropsy. incidental hepatic lobe torsions have also been identified in three adult new zealand white rabbits that died from pasteurellosis (weisbroth, ) . three cases of hepatic torsion in pet rabbits were reported by wenger in (wenger et al., ) . all rabbits presented with an acute onset of lethargy, anorexia, abdominal pain, pale mucous membranes, and jaundice. one rabbit also had hematuria. another report of caudate liver lobe torsion also described a rabbit that was jaundiced, anemic, and anorexic, with elevated alanine aminotransferase. torsion of the caudate liver lobe was seen at necropsy (fitzgerald and fitzgerald, ) . in all reported clinical cases, rabbits were euthanized, or died during postoperative recovery. calcium carbonate and triple phosphate crystals are present in the urine of normal rabbits. these crystals contribute to the cloudy consistency of the urine (williams, ) . a -year retrospective study of hematuria in new zealand white rabbits was conducted by garibaldi (garibaldi et al., ) . physical examination, laboratory tests, radiography, and postmortem examination were utilized in most cases to verify the presence of hematuria and to determine its etiology. uterine adenocarcinoma was diagnosed in two rabbits. three rabbits had uterine polyps with hemorrhage. renal infarction with hemorrhage was diagnosed in three rabbits. urolithiasis with secondary urethral obstruction and hemorrhagic cystitis was identified as the cause of hematuria in four rabbits. other causes of hematuria included chronic cystitis, disseminated intravascular coagulation, bladder polyps and pyelonephritis. hematuria of undetermined origin was observed in one rabbit which emphasizes that hyperpigmented urine should be a rule out in all cases of suspected hematuria in rabbits (garibaldi et al., ) . one case of urolithiasis with hydronephrosis in a new zealand white rabbit was also reported (labranche and renegar, ) . this condition must be distinguished from hematuria caused by endometrial venous aneurysm in female rabbits (bray et al., ) . herniation of the kidney along with perinephric fat has been reported (suckow and grigdesby, ) . the affected rabbit was clinically normal except for a subcutaneous mass that had passed through the body wall. the precise etiology is not known, although it was speculated that herniation might have occurred as the result of unreported trauma. occlusion of the nasolacrimal duct, presumably due to accumulation of fat droplets, has been described as a putative cause of epiphora in some rabbits (marini et al., ) . although the obstruction occurred at the dorsal flexure, it is not clear if this was due to congenital rather than acquired stenosis. in a retrospective study of rabbits it was determined that the mean age of the rabbits presenting with ocular discharge from the nasolacrimal duct was . years. in rabbits ( %), dacryocystitis was a unilateral finding. no underlying cause could be determined in animals ( %). dental malocclusion was observed in rabbits ( %) and rhinitis in two animals ( %), with one animal showing both signs ( %). one rabbit ( %) presented with panophthalmitis. most animals ( %) received topical antibiotic treatment. regarding the clinical outcome, animals ( %) showed complete recovery, eight rabbits ( %) were euthanized, three ( %) died due to unrelated causes, and three ( %) were lost to follow-up. two rabbits ( %) continued to display signs of dacryocystitis (florin et al., ) . development and genetic differences of complement activity in rabbits influence of pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits rabbit haemorrhagic disease (rhd) and rabbit haemorrhagic disease virus (rhdv): a review candidate vaccine antigens and genes in pasteurella multocida a survey of clostridium spiroforme antimicrobial susceptibility in rabbit breeding vaccination of rabbits against coccidiosis using precocious lines of eimeria magna and eimeria media in benin molecular characterization of pasteurella multocida isolates from rabbits detection of cytokine mrna in the lung during the spontaneous pneumocystis carinii pneumonia of the young rabbit rabbit pasteurellosis: respiratory and renal pathology of control and immunized rabbits after challenge with pasteurella multocida tyzzer's disease syndrome in laboratory rabbits trichoepithelioma in a rabbit transgenic rabbits expressing human lipoprotein lipase effects of sarcoptes scabei var. canis (acari: sarcoptidae) on blood indexes of parasitized rabbits host-seeking behavior of sarcoptes scabei histopathology in hosts parasitized by sarcoptes scabei watanabe heritable hyperlipidemic rabbits. familial hypercholesterolemia animal model: spontaneous adenocarcinoma in aged rabbits wild rabbits -a novel vector for vero cytotoxigenic escherichia coli (vtec) o clostridium spiroforme infection in rabbits dermatophytes in clinically healthy laboratory animals in utero transmission of encephalitozoon cuniculi strain type i in rabbits environmental enrichment for laboratory rodents and rabbits: requirements of rodents, rabbits, and research natural paratuberculosis infection in rabbits in scotland rapid detection of clostridium difficile in feces by real-time pcr metabolic, traumatic, mycotic, and miscellaneous diseases of rabbits fresh fruit and vegetables as vehicles for the transmission of human pathogens vitamin d toxicosis in commercially reared rabbits nicorandil normalizes prolonged repolarisation in the first transgenic rabbit model with long-qt syndrome both in vitro and in vivo intracranial teratoma in a domestic rabbit o serogroups, biotypes, and eae genes in escherichia coli strains isolated from diarrheic and healthy rabbits functional and morphological organization of the rabbit sinus node association of iota-like toxin and clostridium spiroforme with both spontaneous and antibioticassociated diarrhea and colitis in rabbits pathogenomics of pasteurella multocida viral diseases hydrometra in a new zealand white rabbit endometrial venous aneurysms in three new zealand white rabbits efficacy of enrofloxacin in the treatment of respiratory pasteurellosis in rabbits studies based on a malignant tumor of the rabbit. i. the spontaneous tumor and associated abnormalities glucocorticoid metabolites in rabbit faeces -influence of environmental enrichment and cage size compendium of normal blood values of laboratory animals with indication of variations development of ocular hypertension in congenitally buphthalmic rabbits epidemiology and risk factors for dermatophytoses in rabbit farms enzymatic activity of microsporum canis and trichophyton mentagrophytes from breeding rabbits with and without skin lesions molecular identification and phylogenesis of dermatophytes isolated from rabbit farms and rabbit farm workers perinatal development of glucogenic enzymes in rabbit liver evaluation of some coagulation parameters in hepatic coccidiosis experimentally induced with eimeria stiedai in rabbits eimeria stiedae: experimental infection in rabbits and the effect of treatment with toltrazuril and ivermectin biotypes and o serogroups of escherichia coli involved in intestinal infections of weaned rabbits: clues to diagnosis of pathogenic strains diarrhea due to escherichia coli in the rabbit: a novel mechanism the digestive system of the rabbit infectious nature of clostridium spiroforme-mediated rabbit enterotoxaemia experimental and spontaneous clostridial enteropathies of laboratory and free living lagomorphs in vitro susceptibility of rabbit strains of clostridium spiroforme to antimicrobial agents structure of rrn operons in pathogenic non-cultivable treponemes: sequence but not genomic position of intergenic spacers correlates with classification of treponema pallidum and treponema paraluiscuniculi strains animal pneumocystosis: a model for man in utero transmission of pneumocystis carinii sp natural transmission of pneumocystis carinii in nonimmunosuppressed animals: early contagiousness of experimentally infected rabbits (oryctolagus cuniculus) obtaining a pneumocystisfree rabbit breeding stock (oryctolagus cuniculus) cryptosporidium sp. rabbit genotype, a newly identified human pathogen sporadic human cryptosporidiosis caused by cryptosporidium cuniculus rabbit feeding and nutrition nutrition and nutritional diseases dermatophytoses in animals expression of recombinant human factor viii in milk of several generations of transgenic rabbits quality of transgenic rabbit embryos with different egfp gene constructs induction of pneumonia in rabbits by use of a purified protein toxin from pasteurella multocida cottontail rabbit papillomavirus (crpv) model system to test antiviral and immunotherapeutic strategies rabbit genetics and transgenic models a behavioral comparison of new zealand white rabbits (oryctolagus cuniculus) housed individually or in pairs in conventional laboratory cages relationship between food and water ingestion in the rabbit infection strategies of enteric pathogenic escherichia coli animal and human pathogenic escherichia coli strains share common genetic backgrounds facial alopecia in the rabbit associated with cheyletiella parasitovorax cheyletiella dermatitis: a mite infestation of rabbit, cat, dog, and man intranasal vaccination of rabbits with pasteurella multocida a: outer membranes that express ironregulated proteins natural pathogens of laboratory animals and their effects on research comparison of the s ribosomal dna sequences from the intracellular agents of proliferative enteritis in a hamster, deer, and ostrich with the sequence of a porcine isolate of lawsonia intracellularis diagnosis of proliferative enteritis in frozen and formalin-fixed, paraffin-embedded tissues from a hamster, horse, deer and ostrich using a lawsonia intracellularis-specific multiplex pcr assay fluorescence-activated flow cytometry in the hematology clinical laboratory disorders of carbohydrate metabolism in infancy altered immune responsiveness associated with encephalitozoon cuniculi infection in rabbits bacillus piliformis' (tyzzer) and tyzzer's disease of the laboratory mouse. i. propagation of the organism in embryonated eggs pneumocystis carinii pneumonia in four mammal species: histopathology and ultrastructure ultrastructure, immunoflourescence, western blot, and pcr analysis of eight isolates of encephalitozoon (septata) intestinalis established in culture from sputum and urine samples and duodenal aspirates of five patients with aids venereal spirochetosis of rabbits: description and diagnosis venereal spirochetosis of rabbits: epizootiology venereal spirochetosis of rabbits: eradication use of ivermectin for treatment of ear mite infestation in rabbits an epizootic of tyzzer's disease in rabbits experimental reproduction of neonatal diarrhea in young gnotobiotic hares simultaneously associated with clostridium difficile and other clostridium strains single primer polymerase chain reaction fingerprinting for pasteurella multocida isolates from laboratory rabbits typing of clostridium perfringens by in vitro amplification of toxin genes escherichia coli o : h in environments of culture-positive cattle herpesvirus systematics respiratory diseases of rabbits pasteurella multocida and bordetella bronchiseptica infections in rabbits pneumocystis oryctolagi sp. nov., an uncultured fungus causing pneumonia in rabbits at weaning: review of current knowledge, and description of a new taxon on genotypic, phylogenetic and phenotypic bases ingestion of rabbit erythrocytes containing cr-labeled hemoglobin by psoroptes spp. that originated on cattle, mountain sheep, or rabbits colonization of rabbits by pasteurella multocida: serum igg responses following intranasal challenge with serologically distinct isolates identification and characterization of three encephalitozoon cuniculi strains treponema paraluis-cuniculi infection in a commercial rabbitry: epidemiology and serodiagnosis atrophic rhinitis in new zealand white rabbits infected with pasteurella multocida naturally acquired pasteurella multocida infection in rabbits: immunological aspects naturally acquired pasteurella multocida infection in rabbits: clinicopathological aspects hypervitaminosis a and reproductive disorders in rabbits ferrets, rabbits, and rodents production of recombinant human protein c in the milk of transgenic rabbits from the f generation development of pcr protocols for specific identification of clostridium spiroforme and detection of sas and sbs genes vaccination against eimeria magna coccidiosis using spray dispersion of precocious line oocysts in the nest box a quantitative polymerase chain reaction assay for detection and quantification of lawsonia intracellularis subclinical proliferative enteropathy in sentinel rabbits associated with lawsonia intracellularis assignment of the agent of tyzzer's disease to clostridium piliforme comb. nov. on the basis of s rrna sequence analysis control of oxyuriasis in rabbits by fenbendazole preliminary observations on enteritis associated with a coronavirus-like agent in rabbits evaluation of pasteurella multocida isolated from rabbits by capsular typing, somatic serotyping, and restriction endonuclease analysis helminth infection in relation to population fluctuations in snowshoe hare silver staining of spirochaetes in single tissue sections effectiveness of a selamectin spot-on formulation in rabbits with sarcoptic mange the effect of the fiber and protein level of the ration upon the cecotrophy of rabbits ribosomal rna sequences of clostridium piliforme isolated from rodent and rabbit: re-examining the phylogeny of the tyzzer's disease agent and development of a diagnostic polymerase chain reaction assay teneur en acides amines des deux catégories de fèces du lapin: caecotrophes et fèces durés virulence genes and antimicrobial resistance profiles of pasteurella multocida strains isolated from rabbits in brazil hepatic lobe torsion in a new zealand white rabbit identification of crystalline material in urine of rabbits renal nosematosis in young rabbits metabolic, traumatic, mycotic, and miscellaneous disease of rabbits clinical presentation, treatment, and outcome of dacryocystitis in rabbits: a retrospective study of cases use of gonadotropic releasing hormone for ovulating the rabbit model influence of a genetically determined atropinesterase on atropine inhibition of the "smoke (dive) reflex" in rabbits intracellular campylobacter-like organism from ferrets and hamsters with proliferative bowel disease is a desulfovibrio sp the clinical chemistry of laboratory animals taxonomy and genetics mandibular prognathism in the rabbit. genetic studies strain differences in the prealbumin serum esterases of jax rabbits buphthalmia in the rabbit. pleiotropic effects of the (bu) gene and a possible explanation of mode of gene action what is your diagnosis? respiratory abscess polymerase chain reaction for diagnosis and species differentiation of microsporidia systemic inflammatory response indicators in rabbits (oryctolagus cuniculus) experimentally infected with sporulated oocysts of eimeria stiedai (apicomplexa: eimeriidae) pathology of protozoal and helminthic diseases toxigenic pasteurella multocida in rabbits with naturally occurring atrophic rhinitis examination of the applicability of a commercial human rotavirus antigen detection kit for use in laboratory rabbits cyclical variations in the excretion of intestinal coccidial oocysts in the rabbit effect of heat and selected chemical disinfectants upon infectivity of spores of bacillus piliformis (tyzzer's disease) tyzzer's disease of rabbits: isolation and propagation of bacillus piliformis (tyzzer) in embryonated eggs development and application of taqman mgb probe fluorescence quantitative pcr method for rapid detection of clostridium piliforme the rabbit as a new reservoir host of enterohemorrhagic escherichia coli a naturally occurring rabbit model of enterohemorrhagic escherichia coli-induced disease renal injury is a consistent finding in dutch belted rabbits experimentally infected with enterohemorrhagic escherichia coli zoonotic enterohemorrhagic escherichia coli: a one health perspective hematuria in rabbits organ systems in adaptation: the temperature regulating system accuracy and coverage assessment of oryctolagus cuniculus (rabbit) genes encoding immunoglobulins in the whole genome sequence assembly (orycun . ) and localization of the igh locus to chromosome tpr homologs in treponema paraluiscuniculi cuniculi a strain inherited neuroaxonal dystrophy in c deficient rabbits fibres in rabbit feeding for digestive troubles prevention: respective role of low-digested and digestible fibre feeding behaviour of rabbits selected drug dosages and clinical reference data medical and surgical management of gastric obstruction from a hairball in the rabbit the complete mitochondrial dna sequence of the rabbit infection with and antibody response to pasteurella multocida and bordetella bronchiseptica in immature rabbits the pathology of experimental respiratory infection with pasteurella multocida and bordetella bronchiseptica in rabbits quantitation of rabbit cytokine mrna by real-time rt-pcr detection of toxigenic clostridium difficile in diarrheal stools by rapid real-time polymerase chain reaction the effect of host's age on the pathology of eimeria stiedae infection in rabbits a spontaneous melanoma in the hamster with a propensity for amelanotic alteration and sarcomatous transformation during transplantation diseases of the rabbit multiple primary tumors in the rabbit paratuberculosis in wild rabbits (oryctolagus cuniculus) inventory of the behaviour of new zealand white rabbits in laboratory cages identification of genes transcribed by pasteurella multocida in rabbit livers through the selective capture of transcribed sequences detection and characterization of cryptosporidium cuniculus by real-time pcr . rabbits. in: reproduction and breeding techniques for laboratory animals. lea & febiger the effects of continuous sulfaquinoxaline feeding on rabbit mortality spontaneous papillomatosis in domestic rabbits antibacterial efficacy and pharmacokinetic studies of ciprofloxacin on pasteurella multocida infected rabbits recessive buphthalmos in the rabbit the effect of environmental enrichment on the behaviour of caged rabbits microbial induction of b and t cell areas in rabbit appendix the biology and medicine of rabbits and rodents pathogenesis of herpesvirus sylvilagus infection in cottontail rabbits normal biochemical and hematological values in new zealand white rabbits early volume expansion during diarrhea and relative nephroprotection during subsequent hemolytic uremic syndrome transgenic rabbit production with simian immunodeficiency virus-derived lentiviral vector syphilis: using modern approaches to understand an old disease uterine torsion associated with either hydrometra or endometritis in two rabbits atrioventricular conduction in mammalian hearts arthropod and helminth parasites isolation of clostridium spiroforme from rabbits proliferative enteropathy involving lawsonia intracellularis infection in rabbits (oryctlagus cuniculus) coecotrophy in rabbits-a circadian function the route of migration of eimeria stiedae (lindemann, ) sporozoites between the duodenum and bile duct of the rabbit the treatment of hepatic coccidiosis in rabbits malignant melanomas in two rabbits proliferative enteropathy of rabbits: the intracellular campylobacter-like organism is closely related to lawsonia intracellularis real-time multiplex polymerase chain reaction assay for rapid detection of clostridium difficile toxin-encoding strains mandibular prognathism in the rabbit: discrimination between single-locus and multifactorial models of inheritance natural mode of acquisition for de novo infection with pneumocystis carinii response of adult new zealand white rabbits to enrichment objects and paired housing hereditary compulsive self-mutilating behaviour in laboratory rabbits spontaneous cryptosporidiosis in an adult female rabbit liver coccidiosis prevented by sulfasuxidine pasteurella associated rhinitis of rabbits: efficacy of penicillin therapy atherosclerotic research a new model of sheep ig diversification: shifting the emphasis toward combinatorial mechanisms and away from hypermutation the rabbit: a diurnal or nocturnal animal? characterization of a novel alphaherpesvirus associated with fatal infections of domestic rabbits an outbreak of fatal herpesvirus infection in domestic rabbits in alaska proteomic analyses of transgenic lqt and lqt rabbit hearts elucidate an increase in expression and activity of energy producing enzymes ovarian abscesses and pyometra in a domestic rabbit an epizootic of shope fibromatosis in a commercial rabbitry enhanced detection of intracellular organism of swine proliferative enteritis, ileal symbiont intracellularis, in feces by polymerase chain reaction eimeria stiedae in rabbits: the demonstration of responses to chemotherapy pure culture of the pathogenic agent of tyzzer's disease of mice molecular approaches in the diagnosis of dermatophytosis pathogenic escherichia coli beat-to-beat regulation of heart rate by afferent stimulation of the aortic nerve implantable stimulating electrode for baroreceptor afferent nerves in rabbits spontaneous renal carcinoma in a new zealand white rabbit an outbreak of massive mortality among farm rabbits associated with cryptosporidium infection growth of tyzzer's organism in primary monolayer cultures of adult mouse hepatocytes the comparative pathology of clostridium difficile-associated disease superovulatory response of pre-and post-pubertal rabbits to commercially available gonadotropins viral infections of rabbits a transplantable rabbit carcinoma originating in a virus-induced papilloma and containing the virus in masked or altered form cloning and sequence analysis of another shiga-like toxin iie variant gene (slt-iiera) from an escherichia coli r strain isolated from rabbit ependymoma in a rabbit deficiency of low density lipoprotein receptors in liver and adrenal gland of the whhl rabbit, an animal model of familial hypercholesterolemia peripheral thermal sensitivity in the rabbit ultrastructural studies of primary congenital glaucoma in rabbits spontaneous nosema cuniculi infection in laboratory rabbits genetic deficiency of the alpha-gamma-subunit of the eighth complement component in the rabbit hereditary c hypocomplementemia in the rabbit hereditary c α-γ deficiency associated with dwarfism in the rabbit environmental factors, clinical signs, therapy and zoonotic risk of rabbits with dermatophytosis biology and diseases of rabbits localization of human coagulation factor viii (hfviii) in transgenic rabbit by fish-tsa: identification of transgene copy number and transmission to the next generation encephalitozoonosis in rabbits new mutant rabbit strain with hypercholesterolemia and atherosclerotic lesions produced by serial inbreeding use of selamectin for the treatment of psoroptic and sarcoptic mite infestation in rabbits urinary calculus and hydronephrosis in a new zealand white rabbit preliminary report on the observation of a coronavirus in the intestine of the laboratory rabbit hereditary hyperlipidemia in the rabbit due to overproduction of lipoproteins, i. biochemical studies proliferative enteropathy experimental and naturally-occuring gastric foreign bodies in laboratory rabbits vitamins in rabbit nutrition: literature review and recommendations farmed rabbits and ducks as vectors for vtec o :h cheyletiella dermatitis: a report of fourteen cases abnormal platelet response to thromboplastin infusion in rabbits deficient in the sixth component of complement value of histopathology, immunohistochemistry, and real-time polymerase chain reaction in the confirmatory diagnosis of encephalitozoon cuniculi infection in rabbits fecal occult blood manifestation of intestinal eimeria spp. infection in rabbit production of transgenic rabbit embryos through intracytoplasmic sperm injection a spontaneous skin basal cell tumor in a black french minilop rabbit peritoneal mesothelioma in the rabbit tyzzer's disease catalytic enzyme activity concentration in plasma of man, sheep, dog, cat, rabbit, guinea pig, rat, and mouse seasonal and sexual influence on rabbit atropinesterase prevalence of lawsonia intracellularis, salmonella spp. and eimeria spp. in healthy and diarrheic pet rabbits inherited diseases and variations expression of human growth hormone in the milk of transgenic rabbits with transgene mapped to the telomere region of chromosome q utilization of cholestyramine resin as a preventative treatment for antibiotic (clindamycin) induced enterotoxemia in the rabbit prolactin-secreting pituitary adenomas with mammary dysplasia in new zealand white rabbits differential conditions for early after-depolarizations and triggered activity in cardiomyocytes derived from transgenic lqt and lqt rabbits complete genome sequence of pasteurella multocida hn , a toxigenic strain of serogroup d resolution of established cardiac hypertrophy and fibrosis and prevention of systolic dysfunction in a transgenic rabbit model of human cardiomyopathy through thiol-sensitive mechanisms dermatophytes isolated from laboratory animals group housing: meeting the physical and social needs of the laboratory rabbit an enzymelinked immunosorbent assay to detect serum igg to pasteurella multocida in naturally and experimentally infected rabbits comparison of sequenced escherichia coli genomes is there a difference between hare syphilis and rabbit syphilis? cross infection experiments between rabbits and hares immunoprophylaxis of dermatophytosis in animals the effect of sulfaquinoxaline on the course of eimeria stiedae infection in the domestic rabbit estimating relative pollution of the environment with oocysts of eimeria stiedae immunology of lagomorphs b cell and antibody repertoire development in rabbits: the requirement of gut-associated lymphoid tissues rhythmic contractile activity of the in vivo rabbit aorta serology of pasteurella multocida in laboratory rabbits: a review microbiologic, radiographic, and anatomic study of the nasolacrimal duct apparatus in the rabbit (oryctolagus cuniculus) worsening of diet-induced atherosclerosis in a new model of transgenic rabbit expressing the human plasma phospholipid transfer protein two encephalitozoon cuniculi strains of human origin are infectious to rabbits lsaa, an antigen involved in cell attachment and invasion, is expressed by lawsonia intracellularis during infection in vitro and in vivo vitamins in animal nutrition clinical and pharmacological properties of ivermectin in rabbits and guinea pigs myeloid leukemia in the rabbit treatment of rabbit chyletiellosis with selamectin or ivermectin: a retrospective case study pathogenesis of shiga-toxin producing escherichia coli pathogenesis of dermatophytosis and tinea versicolor rabbit hemorrhagic disease: a review with special reference to its epizootiology clinical biochemical and hematological reference values in normal experimental animals and normal humans introduction: one health perspective intraepithelial vibrio associated with acute typhlitis of young rabbits infection of different strains of mice with lawsonia intracellularis derived from rabbit or porcine proliferative enteropathy ectoparasites of the wild rabbit, oryctolagus cuniculus (l.) in australia rabbitpox: a model of airborne transmission of smallpox colobomatous microphthalmos in a new zealand white rabbit, arising from a colony with suspected vitamin e deficiency development of a high-sensitivity nested pcr assay for the detection of clostridium piliforme in clinical samples acquired resistance to reinfection of rabbits with eimeria magna the rabbit differs from other mammalian species in the tissue distribution of alkaline phosphatase isoenzymes immunological responses to vaccination following experimental lawsonia intracellularis virulent challenge in pigs clinical efficacy of botanical extracts from eupatorium adenophorum against the sarcoptes scabiei (sarcoptidae: sarcoptes) in rabbits walker's mammals of the world antibiograms of pathogenic bacteria isolated from laboratory rabbits in ibadan eimeria species of the domestic rabbit (oryctolagus cuniculus) pasteurella multocida toxin activation of heterotrimeric g proteins by deamidation life cycle of eimeria stiedae the reproduction of eimeria flavescens and eimeria intestinalis in suckling rabbits the rabbit coccidium eimeria piriformis: selection of a precocious line and life-cycle study protozoal diseases protozoal diseases rapid detection of clostridium difficile toxins from stool samples using real-time multiplex pcr efficacy of an injectable formulation of eprinomectin against psoroptes cuniculi, the ear mange mite in rabbits identification of the cellular receptor of clostridium spiroforme toxin acaricidal activity of eugenol based compounds against scabies mites plasma cell myeloma in the brain of a rabbit an outbreak of encephalomyelitis in broiler rabbits caused by nosema cuniculi diagnostic performance of different fecal lawsonia intracellularis-specific polymerase chain reaction assays as diagnostic tests for proliferative enteropathy in pigs: a review significance of clostridium spiroforme in the enteritis-complex of commercial rabbits biotype, serotype, and pathogenicity of attaching and effacing enteropathogenic escherichia coli strains isolated from diarrheic commercial rabbits three ectoparasites of veterinary interest communicable to man coccidia and coccidiosis parenteral infection experiments with eimeria stiedae transgenic rabbit models for studying human cardiovascular diseases meningitis and subgaleal, subdural, epidural empyema due to pasteurella multocida detection of clostridium difficile toxins from the small intestine and cecum of rabbits with naturally acquired enterotoxemia molecular bases of genetic diversity and evolution of the immunoglobulin heavy chain variable region (ighv) gene locus in leporids rearing germfree cesarean-born rats, mice, and rabbits through weaning spontaneous malignant hemangiosarcomas in two rabbits the behaviour of group penned and individually caged laboratory rabbits genetic characterization of antibiotic resistance in enteropathogenic escherichia coli carrying extendedspectrum beta-lactamases recovered from diarrhoeic rabbits environmental enrichment of new zealand white rabbits living in laboratory cages identification of eae sequences in enteropathogenic escherichia coli strains from rabbits a sebaceous gland carcinoma in a rabbit tyzzer's disease in rabbits in britain pneumocystosis in humans or in corticosteroid-untreated animal models: interactions between pulmonary surfactant changes and pneumocystis carinii in vivo or in vitro growth wild rabbits-a novel vector for verocytotoxigenic escherichia coli o evaluation of available diagnostic methods for clostridium piliforme in laboratory rabbits (oryctolagus cuniculus) further investigation of exposure to lawsonia intracellularis in wild and feral animals captured on horse properties with equine proliferative enteropathy efficacy of an avirulent live vaccine against lawsonia intracellularis in the prevention of proliferative enteropathy in experimentally infected weanling foals transmission of lawsonia intracellularis to weanling foals using feces from experimentally infected rabbits outbreak of sarcoptic mange and malasseziasis in rabbits (oryctolagus cuniculus) characterization of a fibroma virus isolated from naturally-occurring skin tumors in domestic rabbits the pangenome structure of escherichia coli: comparative genomic analysis of e. coli commensal and pathogenic isolates sudden death syndrome in adult cows associated with clostridium perfringens type e cryptosporidium cuniculus in the rabbit (oryctolagus cuniculus) clostridium difficile colitis in a rabbit following antibiotic therapy for pasteurellosis efficacy of cmx as a prophylactic and presymptomatic antiviral agent in new zealand white rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans comparative metabolism of tritiated water by mammals cytotoxicity of bacillus piliformis nutritional muscular dystrophy and neonatal mortality in a rabbit breeding colony laboratory diagnosis of vitamin e deficiency in rabbits fed a faulty commercial ration conventional methods for the diagnosis of dermatophytosis hydrocephalus and cleft palate in an inbred rabbit colony re-description of cryptosporidium cuniculus inman and takeuchi, (apicomplexa: cryptosporidiidae): morphology, biology and phylogeny production of transgenic rabbits a study of the life cycle of eimeria stiedae (lindemann, ) and the immunological response of the host immunocytochemistry of psoroptes cuniculi stained by sera from naive and infested rabbits: preliminary results deficiency of the sixth component of complement in rabbits with an inherited complement defect the life cycle of four intestinal coccidia of the domestic rabbit genome sequence of lawsonia intracellularis strain n , isolated from a sow with hemorrhagic proliferative enteropathy a cottontail rabbit papillomavirus strain (crpvb) with striking divergent e and e oncoproteins: an insight in the evolution of papillomaviruses transgenic rabbit model for human troponin i-based hypertrophic cardiomyopathy exploring transplacental transmission of pneumocystis oryctolagi in first-time pregnant and multiparous rabbit does health and body condition of lactating females on rabbit farms atropinesterase, a genetically determined enzyme in the rabbit wild rabbits (oryctolagus cuniculus) as potential carriers of verocytotoxin-producing escherichia coli proliferative enterocolitis associated with dual infection with enteropathogenic escherichia coli and lawsonia intracellularis in rabbits complement c deficiency protects against diet-induced atherosclerosis in rabbits quantitative rt-pcr profiling of the rabbit immune response: assessment of acute shigella flexneri infection enterocecocolitis associated with intraepithelial campylobacter-like bacteria in rabbits (oryctolagus cuniculus) rotavirus-associated diarrhea in a commercial rabbitry parasites of rabbits in vitro inhibition of clostridium difficile and clostridium perfringens by commercial probiotic strains some factors in the in vitro infectivity and replication of encephalitozoon cuniculi the oxidative status and inflammatory level of the peripheral blood of rabbits infested with psoroptes cuniculi glycogen reserves and their changes at birth cryptosporidium infection in juvenile pet rabbits aortic endograft infection due to pasteurella multocida following a rabbit bite analysis of the expression of platelet antigens cd and cd / in transgenic rabbits with the integrated human blood clotting factor viii gene construct psoroptes cuniculi induced oxidative imbalance in rabbits and its alleviation by using vitamins a, d , e, and h as adjunctive remedial complete genome sequence of treponema paraluiscuniculi, strain cuniculi a: the loss of infectivity to humans is associated with genome decay genetic diversity in treponema pallidum: implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws venereal spirochetosis of rabbits (rabbit syphilis) due to treponema cuniculi: a clinical, serological, and histopathological study coccidiosis of the live rabbit ii, experimental study on the mode of infection of the liver by sporozoites of eimeria stiedae lawsonia intracellularis: getting inside the pathogenesis of proliferative enteropathy gamma interferon influences intestinal epithelial hyperplasia caused by lawsonia intracellularis infection in mice bacillus piliformis infection (tyzzer's disease) in a patient infected with hiv- : confirmation with s ribosomal rna sequence analysis production of two vaccinating recombinant rotavirus proteins in the milk of transgenic rabbits clostridial enteric diseases of domestic animals the young rabbit: a nonimmunosuppressed model for pneumocystis carinii pneumonia helminth, arthropods, and protozoa of domestic animals efficacy of ivermectin against nematodes infecting field populations of snowshoe hares (lepus americanus) in yukon novel bivalent vectored vaccine for control of myxomatosis and rabbit haemorrhagic disease the current status and future directions of myxoma virus, a master in immune evasion phenotypic and genetic characterization of pasteurella multocida and related isolates from rabbits in switzerland altered myofilament stoichiometry in response to heart failure in a cardioprotective alpha-myosin heavy chain transgenic rabbit model glomerular blood flow biochemical modulation of -bromo- '-deoxyuridine and -iodo- '-deoxyuridine incorporation into dna in vx tumor-bearing rabbits polyclonal antibody production rabbit cardiovascular responses during peep before and after vagotomy atropinesterase and cocainesterase of rabbit serum: localization of the enzyme activity in isozymes production of actin-specific adp-ribosyltransferase (binary toxin) by strains of clostridium difficile the laboratory rabbit spontaneous lateral abdominal (lumbar) hernia in a new zealand white rabbit immunization of rabbits against pasteurella multocida using a commercial swine vaccine heat-labile toxinproducing isolates of pasteurella multocida from rabbits protective immunity to pasteurella multocida heat-labile toxin by intranasal immunization in rabbits derivation of pasteurella multocida-free rabbit litters by enrofloxacin treatment immunization of rabbits against a bacterial pathogen with an alginate microparticle vaccine field trial of a pasteurella multocida extract vaccine in rabbits a comparative overview of immunoglobulin genes and the generation of their diversity in tetrapods intracutaneous vaccination of rabbits with the cottontail rabbit papillomavirus (crpv) l gene protects against virus challenge prevention and treatment of encephalitozoon cuniculi infection in rabbits with fenbendazole enteropathogenic escherichia coli prevalence in laboratory rabbits enzootic enteropathogenic escherichia coli infection in laboratory rabbits rearing of germfree rabbits and establishment of an spf rabbit colony pinworm infection in laboratory rodents: a review establishment and characterization of cag/ egfp transgenic rabbit line pneumocystis carinii infection in young non-immunosuppressed rabbits. kinetics of infection and of the primary specific immune response shiga toxin-associated hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: distinct mechanisms of pathogenesis shiga-toxin-producing escherichia coli and haemolytic uraemic syndrome a clinical and pathological study of inherited glaucoma in new zealand white rabbits the effect of combined rotavirus and escherichia coli infection in rabbits rabbit neoplasia novel transgenic rabbit model sheds light on the puzzling role of matrix metalloproteinase- in atherosclerosis studies on the renal circulation comparative morphology of the cardiac conduction tissue in animals water intake in domestic rabbits (oryctolagus cuniculus) from open dishes and nipple drinkers under different water and feeding regimes intermittent medication of sulfadimethoxine and sulfamonomethoxine for the treatment of coccidiosis in domestic rabbits biology of the treponematoses based on studies carried out at the international treponematosis laboratory center of the johns hopkins university under the auspices of the world health organization histiocytic enteritis of rabbits evidence of host adaptation in lawsonia intracellularis infections large-scale management systems and parasite populations: coccidia in rabbits clinical veterinary advisor birds and exotic pets pathogenesis of dermatophytosis thymoma in a rabbit with hypercalcemia and periodic exophthalmus detection of dna sequences identical to pneumocystis carinii in samples of ambient air dna sequences identical to pneumocystis carinii f. sp. carinii and pneumocystis carinii f. sp. hominis in samples of air spora mammalian microsporidiosis serial inbreeding of rabbits with hereditary hyperlipidemia (whhl-rabbit) breeding of a rabbit strain of hyperlipidemia and characteristic of this strain (author's transl) the effect of selective breeding on the development of coronary atherosclerosis in whhl rabbits. an animal model for familial hypercholesterolemia enzyme-linked immunosorbent assay to detect lawsonia intracellularis in rabbits with proliferative enteropathy detection of lawsonia intracellularis using immunomagnetic beads and atp bioluminescence cultivation and characterization of lawsonia intracellularis isolated from rabbit and pig efficacy of simultaneous vaccination with enterisol(r) ileitis and ingelvac(r) circoflextm in a swiss breeding farm neoplastic diseases torsion of the caudate lobe of the liver in the domestic rabbit (oryctolagus) neoplastic diseases microsporidiosis: molecular and diagnostic aspects liver lobe torsion in three adult rabbits ultramicroelectric recording from cardiac pacemaker the effects of group housing on the research use of the laboratory rabbit pasteurella multocida: diseases and pathogenesis practical guide to laboratory animals ophthalmology of exotic pets the effects of ethylene dibromide on semen quality and fertility in the rabbit: evaluation of a model for human seminal characteristics dna polymorphisms amplified by arbitrary primers are useful as genetic markers liver lobe torsion in a rabbit tularemia, plague, yersiniosis, and tyzzer's disease in wild rodents and lagomorphs in canada: a review reference range data base for serum chemistry and hematology values in laboratory animals infectious motor paralysis in young rabbits comparative efficacy of injection routes and doses of ivermectin against psoroptes in rabbits pathology of spontaneous malignant fibrous histiocytoma in a japanese white rabbit (oryctolagus cuniculus) simultaneous identification of three highly pathogenic eimeria species in rabbits using a multiplex pcr diagnostic assay based on its - . s rrna-its fragments the oct promoter-egfp transgenic rabbit: a new model for monitoring the pluripotency of rabbit stem cells flow-volume curves of excised right and left rabbit lungs biochemical parameters of normal rabbit serum a genomic update on clostridial phylogeny: gram-negative spore formers and other misplaced clostridia a blood coagulation abnormality in rabbits deficient in the sixth component of complement (c ) and its correction by purified c origin of complex behaviour of spatially discordant alternans in a transgenic rabbit model of type long qt syndrome key: cord- -npcuo ld authors: gale, robert peter; lazarus, hillard m. title: liaisons dangereuses? new drugs, physicians and the drug industry date: - - journal: bone marrow transplant doi: . /s - - - sha: doc_id: cord_uid: npcuo ld nan us food and drug administration (fda) has approved record numbers of new cancer drugs in recent years. many are relevant to readers of bone marrow transplan-tation who treat acute myeloid leukaemia (aml) including midostarin, gilteritinib, venetoclax, enasideinib, ivosidenib, glasdegib, acute lymphoblastic leukaemia including inotuzumab ozogamicin, blinatumomab, dasatinib, ponatinib and tisagenlecleucel, chronic myeloid leukaemia including ponatinib and bosutinib, plasma cell myeloma including daratumumab, selinexor, elotuzumab, panobinostat and ixazomib, chronic lymphocytic leukaemia including ibrutinib, idelalisib and ofatumumab, lymphoma including vorinostat, mogamulizumab-kpkc, polatuzumab vedotin-piiq, acabrutinib, brentuximab vedotin, zanubrutinib, axicabtagene ciloleucel and tisagenlecleucel, myeloproliferative neoplasm (mpn)-associated myelofibrosis including fedratinib and acute and chronic graftversus-host disease (gvhd) including ibrutinib and ruxolitinib. this is extraordinarily good news but raises questions whether everyone receiving a haematopoietic cell transplant needs and/or benefits from these new drugs and whether physicians were complicit in promoting their approval and subsequent use. these questions are especially important in developing countries where many of these new drugs are not yet or may ever be approved, available and/or affordable. first, do these new drugs really improve survival? for example, many approvals in aml relevant to haematopoietic cell transplantation were based on data from small, sometimes uncontrolled phase- studies. also, many regular approvals were based on surrogate endpoints such as complete or overall response rate, response duration and/or progression-free survival (pfs) rather than survival. for example, between and the us fda-approved cancer drugs, based on surrogate outcomes including based on overall response rate and based on pfs [ ] . all accelerated approvals and one-half of conventional approvals were based on treatment effects with surrogate outcomes. in a recent review fewer than one-half of drugs approved based on a pfs endpoint were shown to improve survival or quality-of-life (qol) [ ] . similarly, between and the european medicines agency (ema) approved cancer drugs only one-half of which were proved to increase survival or improve qol [ ] . another problem with several new drug approvals is the choice of an inappropriate comparator therapy in randomized phase- or phase- trials. finally, many of these approvals were based on analyses of hazard ratios rather than a preferred mean restricted survival time [ ] . another issue is the magnitude of benefit conferred by new drugs like midostaurin and how they should be used in persons with aml with a flt mutation. in the randomized study of midostaurin percent of subjects received an allotransplant with an important imbalance between the midostaurin and placebo cohorts in subjects transplanted in st complete remission ( % versus %; p = . ) [ ] . elsewhere my colleagues and i explain this p value does not mean there is no difference in transplant rates between the arms [ , ] . rather, this p value means it is very likely transplant rates are different and that the null hypothesis is simply not a good statistical model of these (or more extreme) data. more importantly. although the trial reported a survival benefit of pretransplant midostaurin, many physicians fail to appreciate midostaurin was stopped at the time of transplant and that there are not data supporting giving midostaurin after a transplant regardless of whether it was given pretransplant. our informal survey indicates most transplant physicians continue giving midostaurin despite this lack of supporting data. their motto seems: it can't hurt. (sounds like president trump promoting chloroquine, hydroxychloroquine and bleach for covid- .) but who knows? some data suggest one reason many new drugs gain favour with physicians and patients is because they are promoted by nationally or internationally by disease experts often referred to as key opinion leaders (kols) and by drug companies, often in media advertisements. une liaison dangerous? this may be so in some instances [ ] . however, there are several complex considerations here. kols are frequently principle investigators in the clinical trial(s) resulting in a new drug approval. often, they believe, sometimes strongly or even too strongly, the new drug is an important advance. in psychology this process is known as confirmation bias. having invested several years studying a new drug, often with considerable effort and problems working with ethical committees, clinical research organizations (https://www.ashclinicalnews.org/viewpoints/ editors-corner/contract-research-agonizations/); sometimes known as clinical research aggravations), drug company study managers etc. people want to believe their effort worthwhile. otherwise one would seem to have wasted their time, energy and perhaps destroyed your marriage, missed your children growing up, both or perhaps something even worse (a fling in cancun?). but we need to acknowledge other considerations such as the requirement to publish for academic promotion and advancement. it is far easier to publish a study claiming a new, typically more expensive drug is better than an old, typically cheaper drug than the converse. and there are also some less altruistic considerations. everyone likes to address a large, admiring audience, have your headshot (typically of you years ago) projected on a huge screen, travel abroad, be feted at a reception and dine in le bernadine in new york, the ivy in london or la tour d'argent in paris. this behavior is human nature and we cannot unfairly fault them. generic drug makers are likely to take you and the meeting organizers to nathan's famous hot dogs in coney island for dinner (excellent but expensive; currently $ . usd; for $ . ), no fries or, for europeans, traditional pie 'n' mash with eels at cockney's at portobello road, london w ru (£ ). everyone likes to be liked. in contrast, consider a world where drug companies do not develop new drugs for the diseases we need to treat. first, we would be left with methotrexate and corticosteroids to prevent or treat gvhd. almost all new drugs we use in the past years have come from drug companies, not academia. but there are other far-reaching implications. for example, annual educational meetings such as those of the recent transplantation and cellular therapy (tct) meeting in orlando and the european bone marrow transplant group (ebmt) meeting in frankfurt would have rather than attendees. about onethird of the attendees are drug company employees or physicians sponsored to attend the meeting by drug companies. much of the funding for these annual meetings comes from the drug industry, not registration fees. tct and ebmt charge drug companies substantial monies for exhibition space and for the opportunity to present their new drugs in so-called product theatres. imagine an exhibition space at one of these meetings without drug company booths. it would look like grand central terminal devoid of people with only the central lonely information kiosk. a world without free cappuccino or frozen yogurt, video games, giveaways for which physicians earning >$ , per year are willing to que for min. amazing. blood and marrow trans-plantation is filled with advertisements for new drugs. i doubt many journals would be able to achieve widespread distribution at a reasonable cost to society members without advertising income. likewise, their websites are where you are bombarded by unsolicited advertisements for new transplant-related drugs. and think of the exhibit areas at the tct and ebmt meetings. our point is that although its popular to disparage the drug industry for promoting new drugs with sometimes marginal benefits and high costs, the medical community benefits greatly from the investment of these drug companies. much of our medical education in diverse areas is indirectly supported by the drug industry. our lives would be entirely different if drug companies developing and promoting new drugs ceased to exist. and we would be eating hot dogs at nathan's rather than black cod in miso at nobu. remember, the estimated cost of bringing a new cancer drug to approval is about $ million usd [ ] . these monies come from drug company research and development and need to be returned to stockholders with a profit. have we a solution to these potential liaisons dangereuses likely to work? no. it is unreasonable to expect drug companies not to promote drugs they have developed at great cost. professional societies and publishers are addicted to drug company support. individual investigators fight to participate in clinical trials of interesting drugs. coinvestigators fight for lead authourship on publications of successful drug trials which come with designation as a kol and extensive travel on what are labeled educational symposia. regulatory agencies such as us fda and ema have helped curb inappropriate drug labeling and promotional activities but have limited jurisdiction and are subject to political influences. in the us, fda is required by law to approve any drug determined safe and effective whether or not the new drug is safer or better than a current drug. price is dictated by the drug company, not the fda. cost control (if any) lies with the centers for medicare and medicaid services (cms), payor for americans without medical insurance and for persons > years and with pharmacy benefit managers who affect discounts, not price. moreover, us physicians can prescribe any fda-approved drug in settings different from those for which the drug was approved, a practice termed off-label use. again, the only control of off-label use are payors. controls of drug use and pricing are different in some other countries such as the uk where approval based on a determination of safety and efficacy is done by one health authority (medicines and health care products regulatory agency) and appropriateness of use and price are determined by another agency (national institute for health and care excellence (nice). can we correct the threat of liaisons dangereuses? there are some rays of hope. in the us cms and the state children's insurance program are required to enforce the physicians payments sunshine act which requires drug companies to collect and track all financial relationships with physicians and teaching hospitals. the goal is to increase transparency of financial relationships between health care providers and drug companies and uncover potential conflicts of interest. the bill also allows states to enact additional requirements which several states have done. another step is that some universities have limited or completely restricted participation of their faculty in promotional activities. however, data on effectiveness of this ban is far from promising [ ] . for example, in a cohort of academic oncologists at us public medical schools two-thirds received payments from the drug industry in accounting for > % of their annual salary. recently, there has been considerable controversy over participation in china's thousand talents plan under which us academic physicians have established relationships with chinese universities and, in some instances, drug companies receiving received substantial research and personal monies. the fbi is currently investigating these relationships which have led to the firing of several prominent physician scientists. none of these developments is surprising. for example, us medical schools have been selling themselves for a price. for a mere $ million david geffin was able to have the ucla school of medicine, a state institution, named for him. and ucla medical center is named for ex-president ronald reagan after his friends donated $ million. (full disclosure: rpgs wife is in the case family of case western reserve university.) it would seem the california board of regents would be on shaky moral ground trying to control physicians' drug prescribing activities. the truth is physicians and the drug industry have a symbiotic relationship. physicians like to complain but nobody really wants change. but there is hope because what ultimately saves us from these liaisons dangereuses is the moral compass of most physicians who want to do what's best for their patients. our bottom line is some of these new drugs are important advances such as cyclosporine, mycophenolate mofetil and several new antibiotics and anti-fungal drugs. however, the impact of many new approved drugs on transplant outcomes is mostly modest and not everyone needs them. health care resources need to be used to reduce infant mortality, increase childhood vaccination rates, eradicate malaria etc. and most recently to combat the sars-cov- pandemic and treat covid- ; these new drugs are unlikely to be the most effective investment of health care resources, especially in developing countries. despite the above comments, criticisms and admonitions we are standing by to renounce all of these potential liaisons dangereuses if a drug company offers to sponsor us to lecture on a new drug for transplant recipients in milano with dinner at cracco thrown in buon appetito. surrogate endpoints in oncology: when are they acceptable for regulatory and clinical decisions, and are they currently overused cancer drugs approved on the basis of a surrogate end point and subsequent overall survival. an analysis of years of us food and drug administration approvals availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by european medicines agency: retrospective cohort study of drug approvals - uses and limitations of the restricted mean survival time: illustrative examples from cardiovascular outcomes and mortality trials in type diabetes midostaurin plus chemotherapy for acute myeloid leukemia with a flt mutation what is the p-value anyway? what is the (p-) value of the pvalue? following the script: how drug reps make friends and influence doctors research and development spending to bring a single cancer drug to market and revenues after approval comparison of industry payments in with annual salary in a cohort of academic oncologists acknowledgements rpg acknowledges support from the national institute of health research (nihr) biomedical research centre funding scheme. key: cord- -jisp l authors: meyers, keith; thomasson, melissa a. title: can pandemics affect educational attainment? evidence from the polio epidemic of date: - - journal: cliometrica (berl) doi: . /s - - - sha: doc_id: cord_uid: jisp l we leverage the largest polio outbreak in us history, the polio epidemic, to study how epidemic-related school interruptions affect educational attainment. using polio morbidity as a proxy for epidemic exposure, we find that children aged and under, and school-aged children of legal working age with greater exposure to the epidemic experienced reduced educational attainment compared to their slightly older peers. these reductions in observed educational attainment persist even after accounting for the influenza epidemic of . the global covid- pandemic in early led to severe disruptions in nearly all aspects of life. stay-at-home orders closed schools and non-essential businesses, generating widespread unemployment and large declines in economic activity that cannot yet be fully assessed. the social and economic costs of this crisis have been widely felt. a united nations report suggests that global gdp could decline by % (united nations ), while the managing director of the international monetary fund stated that she anticipates that the pandemic will generate "...the worst economic fallout since the great depression," with global gdp contracting by % (gopinath ) . according to unesco, over . billion students, almost % of all learners, have had their schooling disrupted by this crisis. at least countries have closed schools in response to the covid- threat, which may interrupt human capital accumulation in children and contributes to the social costs of the pandemic (unesco ). while most people alive today have never witnessed this scale of the pandemic, research on other epidemics may provide insights into the possible magnitude of the disruption. in this paper, we examine the polio epidemic to measure how it impacted the educational attainment of children during the outbreak. the epidemic is unique in that it was the first and largest major polio epidemic in the usa and was one of the first major public health crises many nascent public health departments faced. the epidemic proved to be the first of many outbreaks that would continue until the advent of the salk vaccine in , although trevelyan et al. ( ) suggest that the epidemic was more intense than subsequent outbreaks. while smaller in magnitude than the more famous - spanish flu, the polio epidemic started in new york city and new jersey, but then spread across the usa, resulting in mass quarantines and prolonged school closures at the start of the - academic school year. the polio epidemic may have affected educational attainment in two ways. first, infected children may have missed school during the period of their illness and recovery. second, even children who did not have symptoms missed school during periods of closure or because their parents refused to send them to school. thus, we leverage geographic variation in the severity of the epidemic, as well as the fact that polio differentially affected children of different ages, to measure how the disease affected the educational attainment reported by these children as adults in the census. children living in areas with high polio morbidity were more likely to be infected and more likely to endure school closures than children in less-affected areas. children under were more susceptible to polio, yet children aged and older may have been more likely to quit school during a prolonged closure and join the labor force. during the ebola outbreak, five million children in africa faced school closures (sifferlin ) . schools in sierra leone were closed for nine months, and schools in guinea and liberia were closed for six months (sifferlin ; paye-layleh ) . in nigeria, schools that were supposed to open in august remained closed until october (bbc news ). studies examining the impact of the sars outbreak on the chinese economy show that it resulted in temporary negative shocks to tourism, retail sales and personal consumption, as well as a . % reduction in gdp (siu and wong ; hanna and huang ) . more recent studies of the impact of ebola on the countries of guinea, liberia and sierra leone suggest that "aversion behavior"-the actions taken by people to avoid illness, and the actions taken by investors as they anticipate these behaviors-led to a loss of $ . billion in , or about % of their combined gdp (thomas et al. ) . prior to , most of the us population had limited experience with the poliovirus. while minor and relatively isolated outbreaks occurred previously in the usa, the outbreak affected more than three times the number of people relative to previous years. in , . cases of polio were reported per , people, compared to the - rate of . per , population (paul ; nathanson and kew ) . the outbreak had greater rates of morbidity than later epidemics, and there is evidence that the epidemic may also have been under-reported (nathanson and kew ). our results show that children born in states with more reported polio cases had lower educational attainment compared to slightly older birth cohorts who would have already completed schooling before the - school year and that the decline in educational attainment varied depending on their age during the outbreak. we find that a one-standard-deviation increase in polio intensity reduced years of completed schooling by . years for children between the ages of and in . for children who were and under during the epidemic (and who were most susceptible to polio), a one-standard-deviation increase led to a . year reduction in years of completed education. these results are robust to controlling for - influenza intensity. polio is caused by the poliovirus, an enterovirus transmitted fecal-orally. evidence on egyptian stele (depicting an adult with a withered leg and crutch) dating from - bc suggests that polio has existed for thousands of years (nathanson and kew ) . although the existence of polio dates to antiquity, it was not until the late th century that epidemics began occurring in the usa and europe. the most plausible explanation for this pattern is that before the late th and early twentieth centuries, most people were probably exposed to polio during infancy when infants had circulating maternal antibodies that made the infection much less severe. over the next years, improved public sanitation delayed exposure to the virus, thus increasing both the age of primary infection and the severity of the illness, since maternal antibodies were no longer circulating. as a result, epidemics that became increasingly severe were reported each summer and fall, and the average age of persons infected increased (nathanson and kew ; centers for disease control and prevention ) . in , there were over deaths and , more documented infections, numbers that eclipsed those of previous (and subsequent) epidemics (lavinder et al. ; trevelyan et al. ) . table details the number of reported polio cases and deaths by state during the epidemic. nearly every state reported polio cases, with massachusetts, new york, new jersey, and connecticut reporting the highest numbers of reported polio infections. while much of the epidemic was in the northeastern usa, there were also sizable outbreaks in minnesota, montana and mississippi. it is important to note that while cities may be more heavily impacted by modern epidemics, polio was unusual in that it was precisely better hygiene that predisposed victims to a later, and more severe, onset. in places with poor sanitation, children would have been exposed at much younger ages (often infancy, without obvious symptoms) and be less likely to suffer a severe case. while many cities had improved sewer and sanitation (thus leading to the large flare of the epidemic in ), rural areas had traditionally been "healthier" places to live from a sanitation standpoint. lavinder et al. ( ) note that the epidemic was more prevalent and intense in small towns and the country than in large cities, and "...not due to mere chance but to some fundamental law" (p. ). the outbreak generated substantial fear. commonly known as "infantile paralysis," polio often caused mild (or no) symptoms but could attack the nervous system and cause permanent paralysis. little was known about how the disease was spread, and no vaccine for polio would be available for another forty years. the disease transcended class lines and affected the poor and the rich alike. in new york city, for example, a large share of cases occurred among native-born children living in single-family dwellings with clean surroundings and indoor toilets (lavinder et al. ). actions taken to curb the spread of polio public health officials struggled to contain the outbreak, which began in june and lasted until november. as the disease spread, officials became increasingly desperate. to prevent the spread of the epidemic and allay public fear, officials implemented various non-pharmaceutical interventions, such as strict quarantines. placards were also placed in front of homes of infected individuals to notify the community of the public health risk. in at least one case, a child suffering from polio was forcibly removed from his home to a hospital, against the wishes of his parents (emerson ) . in new york city, children ages and under were prohibited from leaving new york city for travel unless they produced "... a certificate that the premises occupied by them were free from poliomyelitis, and had been free from this disease since january , ." this was supplemented by a medical examination of such travelers at the point of departure (emerson ) . in new york city and philadelphia, health officials ordered the city streets to be washed with millions of gallons of water each day (offit ; rogers ) . government policy also called for a ban on public gatherings in areas where numerous cases were reported (emerson ) . in the summer of , new york public health officials barred children from movie theaters and libraries, closed sunday schools and banned picnics (the new york times c, e; rogers ) . fears that domesticated animals could spread the disease led to the extermination of , cats and dogs (the new york times b). even though drastic measures were undertaken to control the spread of the disease, hundreds of new infections were reported every week. as autumn approached, fears that afflicted youths would infect their peers and a belief that quarantines could limit the virus' spread led many school districts to delay the start of the school year until the epidemic waned. as the new york department of health noted, "the unprecedented virulence and extent of the existing epidemic, and unfamiliarity with the disease, has engendered in the public such a state of mind that concession to public alarm seemed advisable" (emerson ) . the extent and nature of these closures varied across political and geographic divisions of the usa due to the decentralized structure of the nation's public health (the new york times d) . newspaper accounts show numerous other cities nationwide joined new york in postponing the start of school. philadelphia delayed opening schools until september th (and then to october nd), and both washington, d.c., and fort wayne schools were not reopened until october nd (the washington times company ; evening public ledger a, b) . schools closed across the nation even in states with small numbers of cases. for example, some schools closed in seattle, with only five cases reported (the tacoma times ) . but, even when schools may not have been officially closed, there is evidence that parents worried about sending their children to school. for example, even after the delayed reopening in new york city, worried parents withheld their children from school; up to , students were absent the first few weeks after schools opened, and the district announced "leniency" for parents who failed to send their children to school (the new york times a). to gain insight into the extent of school closures nationally and when they occurred, we searched newspaper records contained in the chronicling america newspaper archive (library of congress ). cities in the most heavily affected areas are most frequently mentioned, but newspaper accounts demonstrate that school closures tended to occur wherever an area experienced a breakout of polio. the epidemic started in june, accelerated in july and persisted through the start of the academic school year. these data most likely represent a subset of school closures, since not all newspapers are covered in the library of congress archive. moreover, our search procedure may have failed to reveal all closures. many newspapers referred to school closures in different cities, or even in major cities in other states. although we found some articles in which a city expressly stated schools would remain open (including chicago, detroit and milwaukee), for most cities we could not ascertain with certainty that they did not close. in fig. , we plot the frequency of school delay announcements in the chronicling america newspaper archive for all newspapers from july , , to november , the search used the entire chronicling america newspaper archive for the usa during the active epidemic. the search required either the word(s) "polio" or "poliomyelitis" or "infantile" or "paralysis" to be referenced on the same page as the words of "school" and "postpone". we allowed the words "school" and "postpone" to be within five words of each other. many articles even referred to the disease as the "baby plague" or "plague". searches for "school closures" also yielded similar results, but with a flatter distribution and wider tails because they often referred to sunday school closures. . school postponement notifications in us newspapers began to increase in the weeks preceding the start of the academic school year (normally around september or september ), peaked during the two first weeks of september and gradually decreased until the first week of october. the latest public school start date we observe in the chronicling america newspaper archive (library of congress ) was october , , although some new england preparatory schools advertised that they postponed their start dates into the middle of october. the newspaper articles also reveal that the persistence of the epidemic caused public health officials and school boards to repeatedly push back school start dates. washington, dc initially planned to start on time, then pushed back the start two weeks to september , and then finally postponed until october . boston, ma did the same. the entire state of pennsylvania also postponed school starts multiple times until the first week of october. to dig deeper into the relationship between city-level school closures and polio outbreaks, we further searched for announcements of school closures in cities for which we have polio morbidity data digitized by van panhuis et al. ( ) . these were cities that voluntarily participated in the disease reporting system conducted by the us public health service, which published this information in its weekly bulletins. we were able to find newspaper accounts of school postponement for of these cities. table in the appendix provides more detailed information on the city names, the dates of postponement, and the name of the newspaper in which we found the information. of these cities, % opened over weeks late, with . % opening on october , . only three (chicago, detroit, and milwaukee) opened on time. figure presents the relationship between weekly polio morbidity in these cities and the timing of school postponements using data from project tycho. we highlight the relationship between the epidemic timing and school postponement by separating this information by the timing of the school starts: schools that started on time, schools that delayed their start dates to a later date in september, and schools that delayed school starts into october. a mass of polio outbreaks in august and september coincided with delayed school starts in many affected cities. polio outbreaks continued in these cities throughout october, and the epidemic ended in november. in fig. , we focus in on a subset of the reported data for cases under per week. for many cities with schools that opened in october there large numbers of reported weekly polio cases throughout september and well into october. schools that postponed only a few weeks into september generally had fewer reported cases of acute polio than either the schools that started in october. in the few schools that we confirmed opened on time, most city week observations report low numbers of polio infections. the exception to this pattern is the city of chicago, which opened schools on time even while polio still spread throughout the community. there is a broad and well-documented literature in economics and in economic history about the impact of early childhood health and economic shocks on later life outcomes (almond et al. ) . within this literature, there are a number of papers that demonstrate the long-run consequences of infectious disease shocks in childhood. beach et al. ( ) show that reduced early-life exposure to typhoid improved later life educational attainment, perhaps by improving cognitive functioning. bhalotra and venkataramani ( ) also find that reduced infant exposure to waterborne disease is associated with improved test scores for girls and improved heights for boys. there is also evidence that individuals who do not contract infectious diseases during epidemics can also be affected. for example, parman ( ) examines the impact of the influenza pandemic on the siblings of those children born during the outbreak and finds that older siblings received an additional three months of education, while younger siblings received slightly less education relative to children who did not have a sibling born during the pandemic. to our knowledge, no one has examined the case of polio in the usa, which is unique in that educational attainment may have been affected even despite the fact that relatively small numbers of people contracted polio. the polio epidemic may have reduced educational attainment through two channels. children who contracted the disease may have missed school while ill, thus reducing educational attainment, although this might depend on whether they contracted a mild form of the disease or paralytic polio. gensowski et al. ( ) find that children who contracted paralytic polio in denmark in were more likely to earn a university degree than children who did not, suggesting that these children shifted investment into education as their comparative advantage moved from jobs requiring certain physical abilities to those requiring more cognitive skills. other children may have experienced reduced educational attainment if they missed school for short periods of time due to school closures or avoidance, or if they delayed entry into formal schooling (for example if the parents of a wouldbe kindergartner decided to wait until the fall of to send the child to school). younger children who have their schooling disrupted even for short periods of time may suffer negative effects. for example, marcotte and hemelt ( ) find that unscheduled school closings due to weather negatively affect student performance on third-grade state assessment examinations. middle-grade students may have lower educational attainment if their learning is disrupted during key periods of development (lloyd ; hernandez ) . whether these effects persist in the long run is less clear. card and krueger ( ) find that men educated in states with higher-quality schools (measured by term length, student-teacher ratio and teacher wage) have higher returns from their schooling. pischke ( ) uses data from a german school district that had a one-time shortening of the school year and finds that the short school year had no negative effect on earnings and employment later in life, although it did lead to more students repeating a grade and fewer students entering higher secondary school tracks. other research does suggest that interruptions in schooling at crucial points of development may have long-run impacts. hernandez ( ) suggests that children in third-grade experience a pedagogical shift from "learning to read" toward "reading to learn." a failure to develop this proficiency in reading on time appears to inhibit human capital accumulation of students and limits the potential to keep pace with their peers. lloyd ( ) suggests that students who perform at a lower level than their peers may be more likely to drop out of school, with third-grade academic performance accurately predicting whether an individual would drop out of school nearly % of the time. in addition to the effect on younger children of missing school, prolonged school closures may have caused older children of legal working age to exit school and enter the labor force. a sizable literature on the effects of compulsory schooling laws suggests that educational attainment is affected by increases in the legal age of school exit, increases in the age at which children can legally work and decreases in the maximum age of school entrance. in , states had legislated as the minimum age for employment in manufacturing (moehling ) . around . % of males and . % of females between the ages of and were active participants of the workforce in , suggesting that many school-age individuals in would have possessed workforce alternatives to education (carter and sutch ) . together, this evidence implies that a notably large portion of youth ages and older had viable and legal employment alternatives available to them in . moreover, if worried parents delayed their youngest children's entry into school for a year, research by deming and dynarski ( ) suggests that these "redshirted" children may have less educational attainment than their non-redshirted peers since they reached a legal working age having acquired fewer years of formal schooling. using the polio epidemic as a natural experiment, this paper examines the effect of epidemics on the educational attainment of children. our primary identification strategy relies on interacting different age cohorts with polio morbidity rates in an individual's birth state. data on polio morbidity at the state level come from lavinder et al. ( ) , who provide comprehensive information pertaining to statelevel polio morbidity covering most of the continental usa. we use the data from lavinder et al because the us public health reports do not include areas with only a few cases (us surgeon general and us public health service ). in all specifications, we interact data on polio morbidity with dummy variables for an individual's age in , since children of different ages may have been differently affected by polio. given that nearly % of children infected by polio before were under the age of , they may have been more likely to experience the effects of polio directly than children of older ages (nathanson and kew ) . on the other hand, children who were and over may have been more likely to leave school for the workforce than children of younger ages. a priori, we expect children under and children ages or older to have their educational attainment impacted at a greater rate than those between the ages of and . we use polio morbidity as our primary data for two reasons. first, complete data on school closures are not available, and state-level data on attendance is not reported for the - school year. second, polio morbidity data enable us to capture both the direct and indirect impacts of polio on children. polio may have directly affected school attendance for the children who contracted the disease. since do we not have information on whether specific individuals contracted polio, we instead rely on the polio case (notification) rate in an individual's birth state. in addition, the epidemic may have indirectly affected children who missed school either because schools closed, or because fearful parents kept them at home. schools in areas with higher rates of polio were more likely to close, and parents were more reluctant to send their children to school even when schools were open. relying on school closure data may fail to capture some of these "avoidance" behaviors. for example, data on average daily attendance for five boroughs in new york city prior to , information on enrollment, attendance and length of the school year was reported in the annual report of the us commissioner of education. however, in , the office switched to reporting biennially, and the information was not reported in / (u.s. bureau of education ). to try to disentangle the school closure effect from other effects, we did run regressions using a sample of of the cities we found specific closure dates for in our search of newspapers that also were big enough to be listed as a place of residence in the census. while statistically significant in one specification, results (available upon request) show the same general pattern we describe below. (available only between and ) indicate that average daily school attendance in new york city fell in the - school year, as shown in fig. . we measure polio epidemic exposure by reported infections at the statelevel so that our main identifying assumption is that people who were school age in would be exposed in their state of birth. this assumption would be violated if children and adolescents migrated between states prior to the epidemic. while we can only speculate as to the number of children who moved across states during childhood, we do know that in , % of people were residing in the same state in which they were born. further, migration would bias the treatment effect toward zero if migration prior to the epidemic was not systematically correlated with polio morbidity. using data from the us census, we find that the difference between state of birth and state of residence in is less of a concern and that assigning polio virulence to state of birth is a reasonable proxy for exposure to the epidemic. in fig. , we present the share of persons who were not observed in their state of birth in the decennial census. on average, % of people ages to in in states that reported polio still resided in their state of birth. to test whether the epidemic influenced the educational attainment of exposed cohorts, we match a sample of white males born between and with the polio morbidity rate in their state of birth, and the years of education they report having in the us census (ruggles et al. ). we restrict the sample to males since they entered the workforce as permanent participants. we also exclude blacks, since margo ( ) finds that the highest grade of school reported in the census does not accurately represent years of schooling received for african americans. table reports summary statistics for the primary sample. equation ( ) represents the reduced form empirical regression used to study the effects of the epidemic on educational attainment: s,a denotes years of completed education for individual i, born in state b, residing in state s in , and born in birth year cohort a. to compare the relationship between polio morbidity in and educational attainment, we compare the educational attainment of persons born between and (who were between the ages of and at the time of the epidemic) to those who were born between and (who were between the ages of and ). this allows us to compare the educational attainment of persons who plausibly could have been in school with those who would have already completed school. in order to test our hypothesis that children of different ages may have been deferentially impacted by the polio epidemic based on their labor market alternatives, we bin them into four age groups: ages - (born - ), ages - (born - ) , and children under age (born - ) . we interact polio morbidity per population ( polio b ) in an individual's birth state with these age-specific cohort groups ( agebin a,j ). the omitted cohort is individuals aged to (born - ). the variables b , s , and a denote state of birth, state of residence in , and age cohort fixed effects. the identification of polio morbidity's effect on educational attainment comes from comparing different age cohorts from the same birth state while controlling for current state of residence, and national shocks common across birth cohorts. state of birth fixed effects control for factors common across persons born in the same state, and state of residence fixed effects control for factors that are shared among persons residing in the same enumeration state. common shocks shared across birth year cohorts, such as wwi, are controlled for using birth year fixed effects. in the full specification, we also include state-level economic and demographic controls for by state of birth, and control for schooling laws that applied to each birth year cohort from each state. these controls are denoted by x b and include doctors per capita in , education expenditures per capita in , the natural log of manufacturing wages per earner in , and the natural log of population in . interacting these controls with age cohort fixed effects allows the effect of these state-level characteristics on educational attainment to vary across different age cohorts. these interactions allow the state-level treatment effect of the epidemic to vary across birth year cohorts. the schooling laws, constructed by lleras-muney ( ), denote the ages of mandatory school entry, age of school exit and age at which children could obtain work permits for each birth year cohort from each state of birth. these laws proxy for idiosyncratic changes in schooling regulations for each state of birth by birth year cohort. finally, i,b,s,a denotes a heteroskedastic error term clustered by state of birth. in our analysis, we run three different regressions, reported in table . columns ( )-( ) report results from estimating equation ( ) with the years of schooling as the dependent variable. column ( ) includes fixed effects for state of residence in , state of birth, and birth year. column ( ) also includes the full set of fixed effects and birth state by age-cohort trends to control for potential underlying geographic trends common across cohorts born in different areas of the country, and column ( ) we thank adriana lleras-muney for providing these data. the mandatory schooling law data start in and continue until . we assign the cohort-specific law by subtracting the year the law was enacted from the age students can leave school. this identifies the birth year cohort to which the law plausibly applied. the laws are assigned for each year of birth by state of birth. in cases where there might be more than one applicable law, we assign the minimum age implied by the laws. in the case of missing values, we linearly interpolate if the missing value is between two birth years. in cases where we cannot linearly interpolate, we assign the schooling law from the closest birth year without a missing value in the state of birth, e.g., if values for birth years and are missing and we have values for , the values for are assigned to the earlier cohorts. this process works for all states except for wyoming where we cannot assign variable values for individuals. inclusion or exclusion of the schooling laws has little effect on estimated regression coefficients. replaces the trend variables with flexible state of birth economic and demographic controls for interacted with age cohort dummies, and adds schooling law controls. all coefficient results discussed refer to our preferred and most restrictive specification, ( ), unless otherwise noted. results presented in table confirm our hypothesis that the polio epidemic of had different effects on educational attainment for children of different ages. schoolaged children who were old enough to have labor market alternatives (i.e., those who were between ages and in ) and those who were living in areas more affected by the epidemic had lower educational attainment than similarly-aged children living in areas with lower polio morbidity rates. this result is robust even in our models with the most restrictive controls. a one-standard-deviation increase in the polio morbidity rate per persons (reported as . in table ) results in persons ages - having around . fewer years of educational attainment on average. the reference cohort of persons ages - had, on average, nine years of education. a back-of-the-envelope calculation suggests that this effect is equivalent to every fifteenth individual completing one less year of education. there is also a statistically significant and negative relationship between polio morbidity and educational attainment for children and under. the estimated coefficient suggests that a one-standard-deviation increase in polio morbidity decreases educational attainment by . years-the equivalent of one in ten people of the cohort completing one less year of education. in contrast, state-level polio morbidity in does not have a statistically significant relationship with educational attainment in individuals who were over , but too young to legally work in most states. the estimated coefficients on the interaction between polio morbidity and persons ages to in are negative, although the standard errors are large and they are not precise zeros. relative to individuals born before , the educational attainment of people born in those years do not appear to be strongly affected by polio morbidity rates. we test whether our results are robust to using two-year age groupings. results (reported in , / and / . the reference birth cohort is / . standard errors are clustered by state of birth and are in parentheses. all specifications include state of birth fixed effects, fixed effects for state of residence in , and birth year fe. economic controls are controls interacted with age cohort dummies. these variables include state-level doctors per capita, education expenditures per capita, log manufacturing wages per earner and log population. cohort schooling laws included proxies for the age of school entry, age of school exit and age of work permit that varies by state of birth and by year of birth * p < . , * * p < . , * * * p < . the appendix) are robust and confirm our main findings: that students with the ability to work legally, and children younger than experienced reduced educational attainment relative to children in the middle grades. in addition to state-level data, we have county-level data on polio morbidity from lavinder et al. ( ) for a select set of states in the eastern usa, as shown in fig. . these county data cover the northeastern part of the usa, which experienced much higher rates of polio cases and deaths than other regions. while we do not have data on county of birth, we can connect this county-level measure of polio intensity to county of residence in and restrict the sample to persons residing in the same state they were born in. essentially, we assume that people living in a particular county in (as long as it is in their birth state) were also born in this county. if we assume that migration within the usa between and is not systematically correlated with polio morbidity in , then migration bias would just introduce classical measurement error in county-level exposure to the epidemic. the results using the county-level polio morbidity in table mirror the results using state-level data. while the estimated coefficients are smaller, the relationship between education and polio is negative and statistically significant for all cohorts ages to in . these results suggest that children living in counties with greater polio cases in , on average, had lower levels of educational attainment than slightly older persons. a one-standard-deviation increase in county-level polio cases reduced the educational attainment of persons born between ages to by . years relative to the reference cohort born a few years earlier. similarly, persons aged - also experienced reduced educational attainment; a one-standard-deviation increase in polio morbidity in this age group reduced educational attainment by . years. children under during the polio epidemic had the largest reductions in educational attainment, with a one-standard-deviation increase in polio morbidity associated with a . year reduction in average educational attainment. measurement error could occur, however, if people move between high-morbidity and low-morbidity areas for reasons related to education-for example, if people born in rural counties moved to more urban counties for jobs. in this case, we may be overstating the impact of polio morbidity on educational attainment at the county level. for this reason, we have more confidence in the state-level results that aggregate rural and urban counties and include state of residence in fixed effects that further control for migration. an alternative method would be to link individuals observed between the and censuses and assume that if they reside in the same county, they were likely born in that county. this could further reduce measurement error, but requires significant resource investment and is still not entirely free of measurement error. we also examine whether our results are robust to two alternative specifications. first, the polio outbreak primarily affected young children under the age of five. as sanitation improved, epidemics in later decades tended to infect older children more frequently. using age-specific infection rates for the polio epidemic from a study by dauer ( ) in boston, we substitute our interaction of the polio notification rate variable with age category bins with a new variable created by interacting the polio notification rate for and the age-specific polio infection rate from dauer ( ) . we assign infection risks of % for persons under age four in , % for persons ages to , % for persons ages to , and % for anyone above the age of . in table , we present the main regressions specifications using this alternative measure of polio epidemic exposure. the negative and statistically significant coefficients in specifications ( ) and ( ) are consistent with our main findings and are larger in magnitude. according to specification ( ), for persons aged four and under, an increase in polio cases by one per people decreased educational attainment by . years. for persons between ages five and nine, the reduction in educational attainment was . years, while educational attainment fell by . years for people aged to during the epidemic. it is also plausible that persons exposed to the polio epidemic were also affected by the influenza pandemic, which killed over , people in the usa. the flu came in three waves. the first, with low mortality, came in the spring of . a second wave associated with higher mortality came in fall/winter , with a third wave arriving in early . we include the - flu mortality rates from garrett ( ), the united states bureau of the census ( ), and the united states bureau of the census ( ) into our analysis, since public health departments were not required to report influenza cases. table provides state-level data on influenza deaths by state in and . to control for the intensity of the influenza epidemic, we include the state-level influenza mortality rate interacted with age bins in our regression, even though the disease was most virulent and lethal in older populations than the children we focus on (i.e., adults of prime-working age). this exercise addresses potential concerns that the polio epidemic is spuriously correlated with influenza intensity. we study the effects of influenza intensity on observed education in for a subset of states used in the main analysis ( of ). results reported in table show that including the influenza death rate and its interactions with age groups does not affect our finding that children of legal working age in states with greater numbers of polio cases had less educational attainment. it attenuates the statistical significance of the epidemic for children ages to in in specifications ( ) and ( ) but strengthens it in specification ( ). the effect of influenza mortality itself on educational attainment is statistically insignificant in specifications ( ) and ( ). in specification ( ), we find influenza mortality increases educational attainment for persons born between and . this result is consistent with the findings in parman ( ) , who shows that families results reported are for white males. sample is restricted to individuals residing in the same state as their state of birth. years of education are top coded at years. age cohorts interacted with polio correspond to birth years / , / , and / adjusted educational investments in children in response to reduced human capital caused by prenatal exposure to the flu: slightly older children with siblings who were prenatally exposed to the flu pandemic experienced increased educational attainment. to further substantiate the main results, we also perform a placebo test comparing men ages to in to reference cohort of those ages to . results, reported in table , indicate that there is not a consistent pattern between reported polio morbidity and educational attainment. there is a small, negative and statistically significant relationship between polio intensity and the level of education observed for the age to cohort at the % level in specification ( ). however, this relationship is not consistent across all specifications, suggesting that polio morbidity at the state level is relatively uncorrelated with unobserved factors that could affect observed educational attainment in . in the appendix, we include an additional specification test using two-year birth cohorts, which do not substantively change our results. our primary results focus on men because they had more workforce opportunities and may have responded differently to polio than women. table reports results from our primary specification on a sample of women in . we find that the polio epidemic affected girls under age in a similar way to men. girls aged - also reported reduced educational attainment in high-polio areas, although not in our most saturated model. in our male sample, we find that boys aged - living in areas with higher polio did not have a statistically significant lower educational attainment than boys living in areas less affected by polio, although the standard errors are large and the results are an imprecise zero. for girls aged - , the adj r . . . estimated coefficients are negative and statistically significant. we are not sure why. in general, males and females had different returns to education, and it might have been that girls, for whatever reason, did not return to school in the same numbers as their male counterparts. the first major polio epidemic in the united states struck in the summer of and persisted into the fall. with over , cases of polio diagnosed, the epidemic tested the nascent system of public health departments. officials engaged in a variety of measures to stem the outbreak, including quarantines, washing streets, and closing public schools. in this paper, we focus on the effect of the epidemic on years of schooling reported by individuals in the us census. educational attainment could have been reduced for infected children, or for children who spent less time in school because their schools were closed or because their parents refused to send them. while we do not have data on school closures, we leverage geographical variation in polio morbidity as a proxy and focus on whether children of differential ages were differently affected. younger children were more likely to have the virus, and older children may have opted to join the workforce instead of stay in school. our results show that children of legal working age living in areas with higher rates of polio infection had diminished educational attainment than similarly aged children living in states with lower infection rates. this result, which is robust and consistent across specifications, does not hold for age groups who were not of legal working age, nor does it hold for slightly older children who had already completed their secondary schooling. we find stronger negative educational effects for children who were most susceptible to the virus and who were age and under during the epidemic. table women: effect of polio notification rate per on educational attainment of age cohorts specifications to are the same specifications presented in the main analysis in table , except these results are for white women. years of education are top coded at years. age cohorts interacted with polio correspond to birth years / , / , and / our results suggest that a one-standard-deviation increase in polio intensity during the epidemic reduced educational attainment by . years for the age - cohort and . years for the cohort age and younger. based on the average reported days in the school year, these numbers suggest that annual attendance declined by roughly days in the age - group and days among children et al. ( ) aged and under. these numbers are not trivial; they are within the range of lleras-muney's ( ) finding that compulsory attendance and child labor laws increased educational attainment by about days. another way of looking at the impact is to look at the aggregate effect in the cohort. for the cohort of children aged - during the epidemic, these numbers suggest that on average, about out of of them had one year less of educational attainment in their lifetime. the impact is even larger among younger children, with one out of every children attaining one less year of education. these cohort-wide reductions in educational attainment suggest that public quarantines, school closures, and parental fear magnified the social cost of the poliomyelitis epidemic, and may shed light on how epidemics can affect even people who do not contract the illness. clearly, school closures, even for short times, may reduce educational attainment among affected children. today, with virtual instruction, it is likely that these effects may be smaller. it is also likely that the impact on high-school completion will be mitigated because many jobs require high school diplomas. nevertheless, greater numbers of students are now enrolled in college. these results suggest that if these students leave school (either because they do not like virtual learning, or have a negative financial shock), they may be less likely to return and suffer from lower overall educational attainment as a result. , / , / , / , / , / , / , / , and / , / , / , / , / , / , / , / , and / we test sensitivity of our main analysis using alternative reference cohorts. the main analysis uses persons who would have been between and during the polio epidemic. we prefer using multiple birth year age bins study the polio epidemic. this is because our age variable is constructed from year of birth, there is some imprecision in lining up school attendance and age in . in particular, some persons who reach the age of in may have started the school year as year olds. we find a relatively negative and consistent relationship between polio virulence and the age someone was in . we redo the main regressions using persons aged - , - , , - , - , and as reference cohorts. we include an additional interaction between polio and the age cohorts removed from the reference cohort as a "placebo cohort." we find results consistent with our main analysis. using single year reference or falsification cohort in a specification using multiple year bins can alter the statistical significance of our results. potential issues arise from using either year olds alone as a reference cohort or using year olds alone as a falsification cohort. our preferred specifications using economic controls attenuate these effects, the regressions with these controls present negative and statistically significant results consistent with the main regression specification (tables , ) . table alternative reference cohort specification with falsification, part specifications to are the specifications presented in the main analysis and use the reference birth cohort is ages to in (birth years / ). specifications to use a reference cohort ages to and persons aged in are in the "placebo cohort." results reported are for white males. years of education are top coded at years. age cohorts interacted with polio correspond to birth years / , / , and / . standard errors are clustered by state of birth and are in parentheses. economic controls are controls interacted with age cohort dummies. these variables include state level doctors per capita, education expenditures per capita, log manufacturing wages per earner, and log population. cohort schooling laws included proxies for the age of school entry, age of school exit, and age of work permit that varies by state of birth and by year of birth. * p < . , * * p < . , * * * p < . table alternative reference cohort specification with falsification, part specifications to are the specifications that use ages to in as the reference birth cohort and persons aged to are in the "placebo cohort." specifications to use a reference cohort age and persons aged to in are in the "placebo cohort." results reported are for white males. years of education are top coded at years. age cohorts interacted with polio correspond to birth years / , / , and / . standard errors are clustered by state of birth and are in parentheses. economic controls are controls interacted with age cohort dummies. these variables include state level doctors per capita, education expenditures per capita, log manufacturing wages per earner, and log population. cohort schooling laws included proxies for the age of school entry, age of school exit, and age of work permit that varies by state of birth and by year of birth. * p < . , * * p < . , * * * p < . childhood circumstances and adult outcomes: act ii is the influenza pandemic over? long-term effects of in utero influenza exposure in the post- u.s. 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last danish polio epidemic human capital and social capital: the rise of secondary schooling in america, - the great lockdown: worst economic downturn since the great depression the impact of sars on asian economies published: the annie e casey foundation lavinder ch, freeman aw, frost wh ( ) epidemiologic studies of poliomyelitis in new york city and the northeastern united states during the year chronicling america: historic american newspapers were compulsory education and child labor laws effective? an analysis from to in the u.s prediction of school failure from third-grade data unscheduled school closings and student performance race, educational attainment, and the census compulsory schooling legislation and school attendance in turn-of-the century america: a 'natural experiment' approach state child labor laws and the decline of child labor from emergence to eradication: the epidemiology of poliomyelitis deconstructed the cutter incident: how america's first polio vaccine led to the growing vaccine crisis childhood health and sibling outcomes: nurture reinforcing nature during the influenza pandemic the impact of length of the school year on student performance and earnings: evidence from the german short school years weekly reports for dirt and disease: polio before fdr million kids aren't in school because of ebola acknowledgements thomasson acknowledges support from the julian lange professorship. we thank see tables , and . the economic impact of ebola on sub-saharan africa: updated estimates for . technical report. world bank group trevelyan b, raynor-smallman m, cliff ad ( ) key: cord- -wyy rvqb authors: ashwell, douglas; murray, niki title: when being positive might be negative: an analysis of australian and new zealand newspaper framing of vaccination post australia's no jab no pay legislation date: - - journal: vaccine doi: . /j.vaccine. . . sha: doc_id: cord_uid: wyy rvqb vaccination rates are an ongoing global concern. many developing and developed countries have rates of vaccination below rates required for herd immunity, for differing reasons. one way in which to communicate information about vaccination to the wider public is via the use of the news media. communication agenda-setting and framing theory generally hold that the news media sets the issues of importance to society and also tells us how we should think about those issues. emphasis framing theory however, would suggest that positively-framed statements in the media may actually be viewed as persuasive in a coercing way, leading to resistance to the messages. further, this theory claims that negative news media is viewed as more credible and therefore, more easily accepted. we were interested to explore the framing of news reports about vaccination and the potential effects this framing may have had on the wider public over the years – in both australia and new zealand (when changes in vaccination policy and publicity respectively were on the agenda). we undertook a content analysis of articles and emphasis frame, type of message, and other variables recorded. in both australia and new zealand, the news media messages were predominately positively framed and yet the vaccination rates of new zealand particularly (where no policy changes mandating vaccination took place) have been decreasing. we suggest the media emphasis on positive vaccination reporting may be having the opposite effect of engendering resistance to vaccination within those who are vaccine-hesitant. vaccination is a contentious issue worldwide (see [ ] for a review). the world health organisation (who) sets immunisation rates of at least % vaccination coverage by [ ] to enhance herd immunity and protect populations from potentially serious diseases. however, rates of immunisation for different antigens vary significantly. global coverage rates in ranged from approximately % for rotaviruses, % for pneumococcal diseases, % for hepatitis b, % for measles (first dose) % for measles (second dose), and % for diphtheria-tetanus-pertussis [ ] . more people now question the necessity of vaccinations in a largely disease-free first-world population [ , ] , and with recent developments in terms of covid- it would be reasonable to assume that this questioning would be minimised. unfortunately, however, recent research has modelled that in fact the opposite might occur with anti-vaccination views being held by the majority in ten years' time if interventions are not put in place [ ] . concerns exist in many countries about falling vaccination rates. for example, the who has expressed concerns about the rise of the anti-vaccination movement in italy, with the incoming government during their electoral campaign ''promising to oppose the pre-existing law that made vaccinations mandatory" [ ] . in both australia and new zealand controversy emerged around the screening of the anti-vaccination film 'vaxxed'. the film attempts to link the measles, mumps, and rubella (mmr) vaccine to autism and is directed by ''discredited gastroenterologist andrew wakefield" [ ] . at the time of writing this article a billboard produced by the new zealand anti-vaccination group warnings about vaccination expectations (waves) was placed on auckland's southern motorway posing the question ''if you knew the ingredients in a vaccine would you risk it?" the billboard was removed the day it was erected after complaints were received by the advertising standards authority [ ] . these examples illustrate how prevalent and current the issue of vaccination is in many countries. the news media play a vital role in communicating vaccination messages to the public [ , ] . while increasing numbers of individuals find their news through social media, over % of stories they are exposed to come from news websites [ ] . therefore, information supplied by the media about vaccines can influence the public's attitudes and beliefs towards them (see [ , , ] ). although the news media can promote pro-vaccination messages, they have also been held responsible for exacerbating the efforts of anti-vaccination groups because of an ''inadequate scientific knowledge base within the media, and an irresponsible tendency towards the emotional" [ ] . speir [ ] goes further arguing the media are tempted to turn single, alleged incidents of adverse vaccine effects into ''major disasters" whereas ''by contrast the successful prevention of diseases in terms of millions of individuals is virtually ignored" (p. s ). given the influence of the media on public attitudes and behaviours toward vaccination, it is important to understand how the media frame vaccination and how these frames impact the wider public. a small number of studies have examined the news media's reporting of vaccination in new zealand and australia separately. in a study of newspaper articles occurring between and , leask and chapman [ ] found the australian newsprint media reported vaccination with an emphasis frame on vaccine-preventable diseases and the issue of low immunisation rates. the coverage also emphasised that the responsibility for vaccination resides with the individual. the threat of vaccine-preventable diseases was conveyed in a number of ways including personification, panic language, stories of personal tragedy, and tales from the pre-vaccination past. these messages were often delivered by representatives of professional medical bodies [ ] . using a larger sample of stories ( ) leask and chapman [ ] found . % of the stories had anti-vaccination statements. these statements contained one or more of the following subtexts: ( ) cover-up -arguments that the real facts about the safety of vaccines was being suppressed. ( ) excavation of the 'facts' -real 'truth' seekers had to find the true facts of vaccination. ( ) unholy alliance for profit -accusations of collusion between government and big pharmaceutical companies, so the latter could increase profits. ( ) towards totalitarianism -vaccination was 'forced' on the community by the government. ( ) us and them -those opposed to vaccination were portrayed as caring parents against the impersonal medical profession. ( ) vaccines as poisonous chemical cocktails -argues vaccines contain dangerous chemicals. ( ) vaccines as cause of idiopathic ills -vaccination blamed for a range of conditions including autism. ( ) back to nature -the body was perfect and able to defend itself without the need to turn to antibiotics and vaccines. a number of stories also portrayed the vaccine debate as a religious crusade between those for and opposed to vaccines [ ] . a more recent study examined the reporting of the hpv vaccine by the australian press finding a number of themes including these: australian pride in vaccine development; details and progress of the national vaccination program; vaccine safety; hpv vaccination's future; whether or not males could and/or should get the vaccine; issues related to sexual activity and the vaccine; and issues about decision-making for acceptance of the hpv vaccine [ ] . a study of new zealand print media between and found the coverage was predominantly neutral towards vaccination ( %) with % of stories framed as positive for vaccination and % opposed [ ] . another study examining headlines used in new zealand newspaper stories reporting the meningococcal b immunisation campaign found that % of the headlines were scientifically inaccurate and another % were misleading [ ] . since the previous australian and new zealand studies cited, a number of events have exacerbated the vaccine debate, including the lancet retraction of the now infamous wakefield study linking the mmr vaccine to autism and the vaxxed film mentioned prior. more importantly for this study is the introduction by australia of the no jab -no pay law in january , a policy not adopted by new zealand. the law meant parents who had children under the age of who were fully immunised or under a government recognised catch-up scheme could receive ''the child care benefit, the child care rebate and the family tax benefit part a end-of-year supplement" [ ] . families who did not vaccinate their children would lose the equivalent of $ . per fortnight, $ per annum, in family tax credits. parents could no longer use conscientious objection or objections on non-medical grounds as reasons to be exempted from losing their tax credits. some states in australia go further with unvaccinated children not being allowed to enrol in pre-schools or childcare centres unless they are vaccinated or have a medical exemption to vaccination. given these more recent events and the policy difference between the two countries regarding vaccination the current study compares newspapers from both countries (a first cross-cultural comparison) to understand any differences in how the reporting is framed, who are the main news sources, the arguments both for and against vaccination that are contained in the stories, and how those who are unwilling to vaccinate their children are labelled. we specifically focus in on emphasis framing theory in making sense of our results. emphasis framing theory argues that when stories or statements are framed in a negative way, they are deemed more credible to readers [ ] . further, positive frames of stories or statements are viewed by readers in a negative light also as attempting to persuade them in some way; for example, advertisements that positively review a product are rightly viewed as attempting to persuade people to purchase that product. these understandings will, it is hoped, lead to implications for the media on best practice reporting of vaccination information. four australian and four new zealand newspapers were selected for the study. newspapers were chosen to replicate previous studies and also for ease of access to archives in contrast to broadcast news. according to roy morgan [ , ] over million new zealanders and . million australians read print newspapers in . most of new zealand's relatively small population (approximately million), is served by four large metropolitan dailies; two in the north island, the dominion post and the new zealand herald, and two in the south island, the press and the otago daily times. there is no national daily newspaper as new zealand's unique and rugged geography has historically hindered the development of one or two national daily newspapers. in contrast australia has two national dailies with the australian, chosen for this sample, having the largest circulation. in order to have an equal number of newspapers from both countries a further three, large, well established metropolitan dailies, two from new south wales, the daily telegraph and sydney morning herald and one from victoria, the the age were selected on advice from an australian colleague (see table ). limiting the sample to these four australian newspapers did mean newspapers from queensland, western australia, south australia, and tasmania were not included. however, newspapers in these states have smaller circulations in comparison to the newspapers chosen. all items, including opinion pieces and letters to the editor (ltes) relating to vaccination or immunisation, were considered for inclusion for the period / / through / / . items were found via a search on the australian/new zealand reference centre database via ebsco host using the following key words: vaccine, vaccinate, vaccination, immunise, and immunization. the first date coincided with the introduction of australia's no jab-no pay law and the cut-off date was decided to be the end of the month in which the study commenced. sourcing articles from the database meant the researchers did not have access to the original newspaper articles and therefore accurate measurements of column inches could not be conducted. in addition, database stories did not always contain photographs and so these were unable to be examined as part of the analysis. a total of articles were found and all were carefully read to ascertain what type of article they were. for example, columns and opinion pieces were identified as different to news articles as the author's name and occupation were often quoted at the beginning of an article and there were often no sources quoted. for example, a story entitled ''attacks on science a call to arms for academics" by the new zealand herald [ ] began with ''dr jarrod gilbert is a sociologist at the university of canterbury. . ." illustrating it was an opinion piece rather than a news story. likewise, ltes were also easily identified as they were short, contained within a group of likeminded items, and the authors were identified by name and the town they came from. once all the items were read, were discarded as they were not about vaccination. for example, one dealt with immunity in terms of legal prosecution. the remaining articles were subjected to a content analysis coding for the following: type of article sources used emphasis of the frame of the story e.g., anti (negative) or pro (positive) towards vaccination labels to describe people unwilling to vaccinate and those who do vaccinate emotive or loaded terms appearing type of anti-vaccination argument leask and chapman's [ ] subtexts were used to identify the anti-vaccination arguments included in articles. we used emphasis framing to determine if the argument of the media story was largely positive in nature (pro-vaccination) or negative in nature (anti-vaccination). a sample of % of the coding of one australian and one new zealand newspaper was subjected to a test of intercoder reliability. agreement was % on framing of the article, % on the type of article, % on number of sources seen, and % on the type of sources. although we found some discrepancies in the type of sources seen, these were minor e.g., a school official versus a state education spokesperson or a medical professional versus a health spokesperson. from the / / through / / the selected newspapers published stories concerning vaccination. a slightly higher number of stories appeared in new zealand newspapers ( versus in the australian newspapers). the majority of the stories were news stories % ( ), % were opinion pieces, and the remaining % were letters to the editor. the number of sources appearing in all the stories were . these included: medical sources -gps, nurses, and representatives from government health bodies politicians -australian prime minister, and mps from both government and opposition parties in both countries, education officials -school principals, school board members university researchers parents of children affected by vaccine preventable diseases anti vax spokespeople government officials -officials from government departments other than health bodies adult sufferer -adults who are suffering from vaccine preventable diseases non-vax parent -parents who do not vaccinate their children parent -sources identified as simply parents and the vaccination status of their children is unknown other -sources who were not lte authors and whose affiliation could not be ascertained fig. shows the differences between sources in the australian and new zealand stories. more medical or health sources were used in the new zealand stories ( vs. ) whereas more political sources appeared in australian newspapers ( vs. ). in all the stories only anti-vaccination activists or spokespersons were used as sources. overall, stories of the entire sample were found to contain a 'negative' emphasis using some of the anti-vaccination arguments identified by leask and chapman [ ] . the most common of these was 'vaccination causes idiopathic ills" appearing times in the stories. the next largest argument mentioned was 'towards totalitarianism' appearing times in the stories. 'unholy alliance' appeared four times, 'cover-up' three, 'poisons' two, and 'back to nature' and 'us and them' once each. 'excavation of facts' did not appear at all. in a number of instances these arguments were not raised by anti-vaccination campaigners, instead those in favour of vaccination raised them to refute these arguments. in addition to analysing the stories for anti-vaccination arguments, the research also identified stories with a positive emphasis, and noted the types of pro-vaccination arguments. these types of arguments appeared in of the stories with stories containing more than one pro-vaccination argument. table illustrates these arguments and their distribution between the australian and new zealand newspapers. as shown in table , the australian newspapers appeared to talk of vaccination more in terms of protecting the community or society than new zealand newspapers which strongly argued that vaccines prevented and protected against disease. another aspect of the stories analysed was the type of emotive terms used by the newspapers analysed. these are shown in table . the new zealand newspapers were more likely to describe increased cases of particular diseases as 'outbreaks' or 'epidemics' unlike their australian counterparts. australian newspapers were more likely to speak about 'vaccine-preventable diseases' and also refer to 'deadly diseases'. twelve stories contained more than one emotive term. both australian and new zealand newspapers were inclined to suggest those opposed to vaccinations were putting their own and other children at risk. the final analysis examined the labels used to describe those persons opposed to vaccination and those persons who supported vaccination. these terms are listed below: two or three terms were used to describe persons who were pro-vaccination. doctors were ''pushing vaccines" and one was called a ''pharma whore". finally, vaccines were labelled ''a victim of their own success". in cross-country comparisons, australia and new zealand do not differ largely from each other in the number of stories published in the / / through / / period. differences were found in the sources most prevalent in vaccination stories between the two countries. the medical/health profession dominated new zealand stories, but political sources dominated the australian media, largely due, it is suggested, to the january arrival of the no jab -no pay campaign, making vaccinations mandatory for families that receive certain government benefits. given the change in the political environment surrounding vaccination in australia, it may be that medical arguments for vaccination become of less import to readers than the potential financial impacts of non-vaccination choices. rates of explicit opting-out of the vaccination schedule for children (known as vaccinerefusal or conscientious objection) are often reported as quite low ( . %) in australia [ ] , ranging from . % to . % in new zealand [ ] . considering that a vaccine refuser's medical concerns regarding vaccination may not be superseded by financial concerns, this suggests that the change in the australian political landscape may have instead impacted on the decisions of those who are vaccine-hesitant (or face other barriers to vaccination such as costs and transport [ ] or antipathy [ ] , but do not identify as against vaccination. emphasis framing theory has been applied in several situations, including psychology, political communication, and public opinion [ ] , and the implications are vast for a number of fields including health. koch and peter [ ] posit that people learn socially to expect credible news from traditional mass news media and to expect this news media to be negative; therefore, the association between negative news media and credibility is built. when news media messages are positive, the credibility relationship is weakened. as positive news media messages about vaccination could also be viewed as advertising, a sense of coercion results from positively framed messages, suggesting that readers may find them less credible in terms of factual information. it could be that readers do not wish to see persuasive information (perceived as akin to advertising) in a perceived 'factual' or 'neutral/balanced' space, particularly with contentious topics such as vaccination. wallack and dorfman [ ] note that the traditional view of mass media with regard to public health is to view it as an ''educational strategy primarily to provide individuals with more information to make better health choices" (p. , italics in original). this view of the media with regard to vaccination positions the media as a 'teacher' or 'authority' on the topic, which may in turn lead to resistance to the message particularly when a reader's own or known other's experiences of vaccination differ [ ] . happer and philo [ ] also argue that journalism is not only about balanced reporting but also sensationalising topics to sell papers claiming that ''news reporting is increasingly shaped by this construction of polarisation and conflict. . ." (p. ). this polarisation in reporting on climate change in happer and philo's [ ] study led to opposing opinions to those emphasised in the media. when looking at sources in the news stories, happer and philo [ ] also found that although readers/viewers trusted the scientist or expert on their topic of climate change, they did not trust the science itself. public trust in politician statements about climate change was also very low. this led happer and philo [ ] to conclude that ''[i]n spite of general sympathy towards the issue and a recognition of its importance, the overall picture of current audience reception was therefore one of confusion, cynicism and distrust about public communications." (p. ). further, even when met with compelling evidence about climate change, the majority of participants who emphasised its importance and changed their attitude toward it, did not show any behavioural changes six months on [ ] . this framing effect has implications for vaccination messages in the media. indeed, studies have found a link between negative information about vaccines in news reports and negative messages about vaccination spreading via social media [ ] , and negative hpv vaccine news reports and subsequent low vaccination rates [ ] . in a systematic review, catalan-matamoros and penafiel-saiz [ ] , noted that of the studies from a variety of countries, % (n = ) were framed around negative information about vaccines. only two studies showed positive framing and messaging about vaccines in news articles [ ] . these findings illustrate the difficulty faced by those trying to communicate to vaccine-hesitant parents. as shown above, negative information is linked to negative messages being spread in social media and lowered vaccination rates. whilst positive information can be seen as a form of persuasion and advertising and thus can cause those who read such information to distrust or resist the messages. in the current study we found that the majority of stories in new zealand and australian media were presented in a positive frame. if the framing effect implied above is correct, positive framing would suggest that readers are less likely to view these messages as credible and view the stories as an attempt to persuade them. when people consciously feel an attempt at persuasion, they tend to resist those messages (known as reactance) [ , , ] , and react negatively to its points (reactance lowers the perceived truth of a message) [ , , ] . therefore, news media that provide a positive frame on vaccination as an activity that people should undertake, may actually be contributing to reactance in the form of lower vaccination uptake and/or lower belief in the efficacy/ need for vaccines. as our study showed, emotively loaded terms and pejorative labels were used in the popular media to argue against anti-vaccination. use of these terms could cause readers to react negatively to the pro-vaccination message. as found by comrie et al., [ ] , immunisation decision-makers reported being disconcerted by vaccination promotional material that denigrated non-vaccinators. in particular, the nz slogan 'be wise, immunise' was touted as suggesting that anyone who did not vaccinate was stupid, which led to defensiveness and reactance. indeed, in new zealand since december , immunisation coverage rates have been decreasing [ ] . this is due to a variety of factors (see [ ] , but the possibility exists that media portrayal of vaccination may be contributing to this decline. it must be noted here however, that vaccine hesitancy and/or uptake is a complex decision-making area, and we do not wish to imply that news articles alone are responsible for declining vaccination rates. social media and how these sites influence vaccination attitudes and actions or inactions is another space of study which needs further research. indeed, it would be useful to determine the relationships (if any) between social media messages and traditional print/online messages, and how those messages are portrayed and taken up by readers/viewers in similar or different ways. decades of framing theory research suggest that the traditional media such as newspapers influence people's views on topics (although it was/is often thought that the framing implies the view e.g., a positive frame should imply a positive view). in this sense however, the positive framing in the media does not appear to be having a positive effect. as a comparison, australian vaccination rates are increasing (for one-and five-year olds since ) [ ] and the majority of the australian stories were also found to be positively framed. however, the political environment of australia is different from that of new zealand, where vaccinations are mandatory to receive specific financial benefits. this would suggest that any media effect is perhaps moderated by the impact of pressing financial concerns for persons receiving such benefits. the emphasis framing interpretation does seem to be a conundrum given that negative reports about vaccination, particularly if viewed as more credible, may have similar negative flow-on effects on vaccination uptake and belief in efficacy or the need for vaccines. the answer may lie in the presentation of neutral, balanced information only in media reports with the goal of informing the general news media public. however, this is easier said than done. balancing positive and negative vaccination information is a contentious field with scientific studies supporting vaccination often 'balanced' in media stories at the same level of credibility as vaccine deniers whom are without a basis in scientific studies. balance as defined by end-users in a previous study [ ] , noted that caregivers making decisions about vaccination for pre-school children wanted clear factual information only, e.g., the number of deaths attributed to the vaccine versus the number of deaths attributed to the disease, and then be left to make their own decisions. this information also needed to come from a credible source. sources that are obviously positive towards vaccination (e.g., government health departments) could be viewed as attempting to persuade, so where this information is to come from and who is to deliver it is a question. comrie et al. [ ] found end-users were particularly convinced by health information from health professionals they trusted. trusting relationships between health professionals and vaccination decision-makers are key but must be combined with the presentation of factual information and perhaps the viewing of that information as neutral and factual, rather than positive/persuading or negatively framed. if information presented in a negative frame leads to perceived heightened credibility and trustworthiness of the source and the message, the implication is that information could be presented in terms of general negative 'worst case scenario's' or the use of 'negative' pictures of children inflicted with the disease. critics of this approach note that picturing the diseases themselves can be perceived as 'fearmongering' by the public and even by health professionals [ , ] . therefore, use of such pictures could be viewed as 'persuasive' but in a negative light, which may have the same negative affect on behaviour as positively framed persuasion. comrie and colleagues [ ] also found that immunisation decisionmakers in general welcomed the pictures of diseases (partial pictures rather than whole child pictures though) as 'factual' information so they could make an informed choice about vaccination. subtilities in presenting such information should be explored in future research. it is interesting to note that some of the negatively framed statements made in media stories were attributed to vaccination supporters who raised these statements only to refute them. therefore, these negative frames were present in a positivelyemphasised article. future research would benefit from focusing on the impact of negatively-framed or positively-framed statements in the context of opposite-emphasised media stories. overall, . % of the stories in the entire sample contained a 'negative' emphasis, whereas leask and chapman [ ] found in their sample of articles in australia that only . % contained a negative emphasis of some type. a partial possibility for this difference could be that a new zealand sample was included in the current study, where a focus seemed to be more on medical information presented (regarding the vaccines), in contrast with the australian media's focus more on political information and community/social benefits. the type of information reported in forms of medical vs political (and individual vs. social), could mean that more negative emphases on vaccination could be found in articles with a more individualistic medical focus. anti-vaccination arguments are often made in terms of the impact on the individual [ ] . this argument also suggests future research to investigate the impact of individualistic vs. community-focused communications on subsequent intention to vaccinate. interestingly, the type of anti-vaccination arguments found by leask and chapman [ ] , were found also in the current study (bar one), albeit at differing frequencies. the findings suggest that the same types of anti-vaccination messages are continuing to be revisited over time, further suggesting that communications in the media and elsewhere have had little effect on addressing concerns behind these messages in the last two decades. leask and chapman [ ] note that the majority of their articles showed a positive or promotional message regarding vaccination, which was also replicated in this study. indeed, this study adds nine types of pro-vaccination messages as developed from the content analysis to leask and chapman's [ ] eight types of antivaccination messages. these types of anti-and pro-vaccination messages provide a framework from which to determine changes or continual patterns in communications over time. in terms of patterns of types of anti-vaccination messages, the top two arguments mentioned in our data were 'vaccination causes idiopathic ills' and 'towards totalitarianism'. leask and chapman's [ ] top two anti-vaccination messages were 'excavation of the facts' (which did not appear in our sample at all) and 'us and them' (which appeared only once). it may be that although similar antivaccination arguments occur over time, the prevalence of these arguments is changing. further, using the new nine types of provaccination messages, as noted above, we can see distinct types of arguments being used in australia and new zealand, who have different political approaches to vaccination. the one similarity is the 'vaccines prevent disease' message which topped both countries' pro-vaccination arguments, but from there, the countries diverge with new zealand focused on 'vaccines protect against disease' and australia focused on 'vaccines protect community/society'. this again could be due to the different individualistic vs. community ideologies of the two nations proposed by this study with regard to vaccination. leask has extended this work in , identifying five parental vaccination group types including the 'unquestioning acceptors', the 'cautious acceptors', the 'hesitant', the 'late or selective vaccinator', and the 'refuser' [ ] . these authors found that different communication strategies were needed in health professional and parent interactions for each of these groups to advocate for quality decisions on vaccination. therefore, it is not only the content of the anti-vaccination argument that must be addressed, but such content must be approached in line with the communication strategies of the parents. this study is a content analysis of articles from two countries. the focus of analysis is on the media reports, and links to wider society's views and actions are suggested. however, this study did not investigate the direct and/or indirect links between media consumption and vaccine uptake and/or views. therefore, this link is an assumption of the research, which may or may not be accurate. some information does suggest that a link exists between media reports on vaccination and subsequent uptake rates or adverse vaccine event reporting (for example, see [ ] and [ ] . although the majority of news media articles studied were positively framed, suggesting that vaccination is portrayed in the media as a useful health activity to engage in, the subsequent expected influence on positive uptake of vaccination and views towards vaccination were not evidenced in wider society. many factors impact a caregiver's vaccination decision, only one of which is the influence of the media. however, it is also possible that the positive emphasis of media stories has an unexpected reverse effect when looked at via emphasis framing theory and its view that negative media stories are viewed as credible, while positive news media stories on topics such as vaccination may lead to unwanted feelings of coercion and therefore reactance/resistance. further research is needed to confirm the relationship indicated by these findings. journalists and media commentators must reflect on the impact of their positioning of health articles. neutral, factual reporting to help construct an informed public is needed, rather than positively or negatively slanted articles. credit authorship contribution statement douglas ashwell: conceptualization, methodology, investigation, writing -original draft, writing -review & editing. improving new zealand's childhood immunisation rates vaccinology: past achievements, present roadblocks and future promises australian department of health. no jab, no pay new requirements fact sheet. immunisation. immunise australia programme australian department of health. immunisation coverage rates for all children australian immunisation register. national vaccine objection (conscientious objection) data making sense of perceptions of risk of diseases and vaccinations: a qualitative study combing models of health beliefs, decisionmaking and risk perception anti-vaccination movements and their interpretations a content analysis of news coverage of the hpv vaccine by how is 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paper. supplementary data to this article can be found online at https://doi.org/ . /j.vaccine. . . . key: cord- -fv authors: cain, william e. title: american dreaming: really reading the great gatsby date: - - journal: society doi: . /s - - - sha: doc_id: cord_uid: fv f. scott fitzgerald’s the great gatsby ( ) is one of the best known and most widely read and taught novels in american literature. it is so familiar that even those who have not read it believe that they have and take for granted that they know about its main character and theme of the american dream. we need to approach the great gatsby as if it were new and really read it, paying close attention to fitzgerald’s literary language. his novel gives us a vivid depiction of and insight into income inequality as it existed in the s and, by extension, as it exists today, when the american dream is even more limited to the fortunate few, not within reach of the many. when we really read the great gatsby, we perceive and understand the american dimension of the novel and appreciate, too, the global range and relevance that in it fitzgerald has achieved. it is a great american book and a great book of world literature. was imperative to read spengler, to sympathize or revolt. it still remains so" (december , ) . retrospectively, fitzgerald could have felt that he must have been reading spengler in spengler in - because this german author's theory of historical degeneration matched the mood that pervades the great gatsby. the decline of the west is a perplexing, lurid text, imposing in manner, epic in scale, intermittently provocative, tedious as a whole. it is impossible to know which of its many sections seized fitzgerald, but the pages on "money" are a potent corollary to his inquiry into american wealth: we can imagine fitzgerald being engaged by them. spengler comments on the growth and expansion of the town, the city, and the accumulation and centrality of money there: as soon as the market has become the town, it is no longer a question of mere centers for streams of goods traversing a purely peasant landscape, but of a second world within the walls, for which the merely producing life "out there" is nothing but object and means, and out of which another stream begins to circle. the decisive point is this-the true urban man is not a producer in the prime terrene sense. he has not the inward linkage with soil or with the goods that pass through his hands. he does not live with these, but looks at them from outside and appraises them in relation to his own life-upkeep…. in place of thinking in goods, we have thinking in money. (vol. , ch. ; spengler's italics) about the enthralling daisy buchanan, gatsby says, "her voice is full of money," to which the narrator nick carraway responds, "that was it. i'd never understood before. it was full of money-that was the inexhaustible charm that rose and fell in it, the jingle of it, the cymbals' song of it" ( ; new york: scribner trade paperback, ). it is not charm alone that money supplies. it also engenders callous indifference; after gatsby's death, nick says about tom buchanan and daisy: "they were careless people, tom and daisy-they smashed up things and creatures and then retreated back into their money or their vast carelessness, or whatever it was that kept them together, and let other people clean up the mess they had made" ( ). wealth has hardened tom and daisy. they are careless, heedless, at a secure and indifferent distance from trouble, never facing the necessity to pay attention or minister to others. it is not that they are thoughtless but, rather, that they "think in money." about money, spengler continues: as the seat of this thinking, the city becomes the moneymarket, the center of values, and a stream of moneyvalues begins to infuse, intellectualize, and command the stream of goods…. only by attuning ourselves exactly to the spirit and economic outlook of the true townsman can we realize what they mean. he works not for needs, but for sales, for money. the business view gradually infuses itself into every kind of activity. at the beginning a man was wealthy because he was powerful-now he is powerful because he has money. (vol. , ch. ) tom does and does not fit spengler's discourse, for, though wealthy, he has inherited his money: he has no vocation or career and has not made anything. tom and daisy are profligate and irresponsible, leading lives that consist, in nick's phrase, of being "rich together" ( ). tom is a formidable physical specimen, as fitzgerald's first description of him, through nick, attests: he was a sturdy, straw haired man of thirty with a rather hard mouth and a supercilious manner. two shining, arrogant eyes had established dominance over his face and gave him the appearance of always leaning aggressively forward. not even the effeminate swank of his riding clothes could hide the enormous power of that body-he seemed to fill those glistening boots until he strained the top lacing and you could see a great pack of muscle shifting when his shoulder moved under his thin coat. it was a body capable of enormous leverage-a cruel body. ( ) tom inhabits a domineering body; his money is embedded in a proto-fascist mass of muscle. he vents a thuggish cruelty, as when he lashes out at his mistress myrtle wilson: "making a short deft movement, tom buchanan broke her nose with his open hand" ( ). fitzgerald was not a philosopher or cultural historian intent on composing encyclopedic arguments. wittgenstein, heidegger, joseph campbell, northrop frye, whittaker chambers, henry kissinger: these are among the figures, very different from fitzgerald, whom spengler influenced. but it is noteworthy that fitzgerald sent his letter to perkins, invoking spengler, in june . his career was faltering, and his effort to thrive as a hollywood screenwriter was failing. the nation remained afflicted by the great depression's tough times (unemployment was %), and the world was at war, with hitler on the march across western europe. the dunkirk evacuation was the first week of june. on june , the day of fitzgerald's letter to perkins, mussolini took italy into the war as an ally of germany. on this same day, the headline of the new york times was: "nazi tanks now within miles of paris." the german army entered paris on june , and france surrendered on june . the literary critic maureen corrigan has stated: "the great gatsby is the greatest… our greatest american novel" (so we read on: how the great gatsby came to be and why it endures, ) . like others, she relates it to the american dream, to american ideas and categories. yet so reflexive has this line of response become that it tends to operate at a remove from fitzgerald's line-by-line writing. if we aim to understand the rich american resonance of the great gatsby, its spengler-like dimension, and, ultimately, its universal range of reference, its impact on readers all across the globe, we must really read it. that we should really read the great gatsby: this sounds obvious. but do we do it? the great gatsby is a book that we assume we already are familiar with, that (so we dimly recall) was assigned to us long ago in high school, that we tell ourselves we must have read. it is akin to moby-dick, uncle tom's cabin, adventures of huckleberry finn, catch- , and other books that we know, or know about, even if we are not intimate with them or in fact have not actually read them. what we need to do, is to pause, take a breath, and approach fitzgerald's novel as if it were new to us. for instance, on the first night that nick attends one of gatsby's parties, he and his companion jordan baker intersect with "two girls in twin yellow dresses" who had met jordan a month ago: "you've dyed your hair since then," remarked jordan, and i started but the girls had moved casually on and her remark was addressed to the premature moon, produced like the supper, no doubt, out of a caterer's basket. with jordan's slender golden arm resting in mine we descended the steps and sauntered about the garden. a tray of cocktails floated at us through the twilight and we sat down at a table with the two girls in yellow and three men, each one introduced to us as mr. mumble. ( ) this passage has the playful exuberance that we associate with dickens, but it is more concise, subtle, and fleeting in its surreal, fantastical quality. we are invited to imagine the moon emerging like a felicitous treat from one of the caterer's baskets, and we watch the tray dawdle in the air as if on its own. this is fitzgerald's evocation of the magic, unreality, and impossibility of gatsby's project to reconnect with daisy. he gives us a controlled rhythm of sentences that amusingly climaxes with the three-man mr. mumble. after a date with jordan, nick returns to his modest house: "when i came home to west egg that night i was afraid for a moment that my house was on fire. two o'clock and the whole corner of the peninsula was blazing with light which fell unreal on the shrubbery and made thin elongating glints upon the roadside wires. turning a corner i saw that it was gatsby's house, lit from tower to cellar" ( ). fitzgerald is presenting an ostentatious effect-a house seemingly on fire, the peninsula blazing, and another house lit up from top to bottom. yet the word "unreal" exposes the illusory nature of the scene. it is amazing and not real, majestic and unnerving testimony to gatsby's imagination, to his yearning to journey backward in time so that he can rewrite the narrative of his and daisy's lives. such a keen image: the light sparking "glints," quick flashes, on the wires. the next day is the date for the afternoon tea that nick has arranged for gatsby's meeting with daisy. as always, in fitzgerald's description and dialogue there are bewitching phrases and images: "the rain cooled about half-past three to a damp mist, through which occasional thin drops swam like dew" ( ). then, daisy arrives: "is this absolutely where you live, my dearest one?" the exhilarating ripple of her voice was a wild tonic in the rain. i had to follow the sound of it for a moment, up and down, with my ear alone before any words came through. a damp streak of hair lay like a dash of blue paint across her cheek and her hand was wet with glistening drops as i took it to help her from the car. "are you in love with me," she said low in my ear. "or why did i have to come alone?" ( ) fitzgerald catches the coy theatricality in daisy's sense of herself. she knows how flirtatious she is, and she performs her attractiveness for nick's enjoyment. it is pleasing to him to observe the performance even as he is aware that daisy knows (and knows that he knows) that he is not in love with her. at the same time, daisy's quickness at producing this impression intimates her fragility, vulnerability, aloneness. who is daisy when she is not on stage? who is she really? gatsby, nick, and daisy enter and wander through gatsby's opulent mansion: "if it wasn't for the mist we could see your home across the bay," said gatsby. "you always have a green light that burns all night at the end of your dock" ( ). green is the color of life, renewal, nature, and energy; it is associated with growth, harmony, freshness, safety, fertility, and the environment. but green is also associated with money, finance, banking, ambition, greed, jealousy, and wall street. this duality makes green the appropriate color for the light that gatsby has gazed at: it has become a symbol for him, at a distance yet clandestinely close, his secret. the mist implies more than gatsby realizes. now at last, he is with daisy. but how clearly is he seeing her? "your home": gatsby does not register the implications of his words. tom is a brute, but he is daisy's husband, and they have a child. their luxurious, wasteful lifestyle, and tom's addiction to adultery: the cozy connotations of "home" do not flow from this family. but it is a family and they do have a home. this is the structure and history that gatsby thinks he can blot out. fitzgerald's next lines convey the depletion in gatsby even as, at this moment, he has daisy nearby and is making contact with her body: daisy put her arm through his abruptly but he seemed absorbed in what he had just said. possibly it had occurred to him that the colossal significance of that light had now vanished forever. compared to the great distance that had separated him from daisy it had seemed very near to her, almost touching her. it had seemed as close as a star to the moon. now it was again a green light on a dock. his count of enchanted objects had diminished by one. ( ) ( ) is gatsby feeling the self-questioning emotions that nick attributes to him? "possibly it had occurred to him": this brooding reflection on nick's part may disclose more about him than it does about gatsby. fitzgerald is communicating to us gatsby's glamor and nick's ambivalent interpretation of it, his projection from himself into the american dreamer whom he scrutinizes with fascination and disapproval. then, as the chapter draws to a close, the peculiar mr. ewing klipspringer plays the piano: in the morning in the evening, ain't we got fun-outside the wind was loud and there was a faint flow of thunder along the sound. all the lights were going on in west egg now; the electric trains, men-carrying, were plunging home through the rain from new york. it was the hour of a profound human change, and excitement was generating on the air. one thing's sure and nothing's surer the rich get richer and the poor get-children. in the meantime, in between time-( ) the tune accents the contrast between rich and poor, and combines the intonation of a loud wind and a counter-intuitive, faintly sounding thunder. fitzgerald gives us once again the imagery of light and electricity, and we hear in nick's voice that he is being mesmerized by a romantic, wistful imagination of his own. nick then turns to gatsby, who has on this fateful day reunited with daisy at last: as i went over to say goodbye i saw that the expression of bewilderment had come back into gatsby's face, as though a faint doubt had occurred to him as to the quality of his present happiness. almost five years! there must have been moments even that afternoon when daisy tumbled short of his dreams-not through her own fault but because of the colossal vitality of his illusion. it had gone beyond her, beyond everything. he had thrown himself into it with a creative passion, adding to it all the time, decking it out with every bright feather that drifted his way. no amount of fire or freshness can challenge what a man will store up in his ghostly heart. ( ) ( ) this sounds dead-on about gatsby, including his magnitude as a dreamer-the word "colossal" appears a second time. yet we should ask how much nick's response is the result of his own desires, hopes, and doubts. he is a reader as much as we are, a reader of gatsby who is struggling to understand this fabulously rich man who is captivating and mysterious, at once intriguing and absurd. nick reports gatsby's thoughts and feelings. is this perception or, again, is it projection? he sees bewilderment in the face and infers ("as though") that it signifies gatsby's uncertainty. the exclamation "almost five years" tells us what gatsby and nick, both of them, are likely to be marveling at. "there must have been," nick surmises: this is his interpretation of, his insistence on, the meaning for gatsby of the reunion with daisy. nick says that gatsby's dream about her and about himself and her as one, his "illusion," was so immense that, surely, she must have fallen short of embodying it. "tumbled" means to fall suddenly and helplessly; a sudden downfall, overthrow, or defeat. this is the verb that fitzgerald ties to daisy here, while he connects gatsby to "thrown himself," which implies someone who is passionate and, also, out of control, desperate. "every bright feather that drifted"-as if gatsby were so transfixed that he creatively works with the merest wisps that flutter by. "no amount of fire or freshness…": fitzgerald could have done without this sentence. it could feel tacked on, a sudden shift from the focus on gatsby himself. but fitzgerald deploys the sentence to point to nick as an interpreter who is stating the lesson that gatsby's dream illuminates for nick himself: "as i watched him he adjusted himself a little, visibly. his hand took hold of hers and as she said something low in his ear he turned toward her with a rush of emotion. i think that voice held him most with its fluctuating, feverish warmth because it couldn't be over-dreamed-that voice was a deathless song" ( ). fitzgerald was an avid reader of poetry, especially keats and shelley and others of the romantic and victorian periods. here, he may be alluding to the phrase "deathless song" as rudyard kipling uses it in "the last of the light brigade" ( ), which is itself a response to and revision of tennyson's "the charge of the light brigade" ( ). kipling's poem describes the fate of the neglected survivors: "though they were dying of famine, they lived in deathless song." gatsby served in combat in world war i, carnage and death enveloping him, entranced by the dream of re-crossing the atlantic to recover daisy. nick tells us what he sees as he looks at gatsby and daisy, but he cannot hear her words. fitzgerald could have written, "the voice…," but instead he writes, "i think that…," again dramatizing the impact of this moment on nick, the observer. fitzgerald brings the chapter to a close: they had forgotten me, but daisy glanced up and held out her hand; gatsby didn't know me now at all. i looked once more at them and they looked back at me, remotely, possessed by intense life. then i went out of the room and down the marble steps into the rain, leaving them there together. ( ) gatsby and daisy are reunited; nick is forgotten, isolated from them, the detail of the falling rain calling attention to his sense of forlorn separateness from them. "intense life" is a compact expressive term for his perception of this couple's exhilarating intimacy. it voices the feeling of being alive at the highest degree that dreamers long for, the dream for them becoming incredibly true. this intense life is not in nick himself. it is in his realization of a vital presence, overwhelming ("a rush of emotion"), miraculous, perhaps too great to be sustained for long, in gatsby and daisy. he is on the outside. when we read the great gatsby, we tend to highlight gatsby and his pursuit of daisy, and the conflict that arises between him and tom buchanan-two wealthy men, each determined to defeat his rival and claim exclusive ownership of the beautiful woman. but fitzgerald chose a first-person narrator, and, in certain respects, nick is the most interesting of the novel's characters. the action of the story that nick is telling took place in june-august , and it is now two years later. much time has passed, and he is back home in the midwest. we might consider how much we could recall of a stretch of incidents and persons, spanning three months, that occurred two years earlier. how trustworthy would our memory be? would we be creating-not so much remembering as inventing-as we reached backward in time to recollect our own and others' words and actions and relationships? when we really read the great gatsby, we should devote attention to nick, to his dreams (or their absence), and to his social and economic position. nick, we learn, is a yale graduate and a veteran of the war. at the outset, his tone is sometimes self-indulgently clever and sarcastic, irritating, even as all the while he-that is, the astute artist fitzgerald-is revealing his own entitled background and fine fortune. nick is not from a very wealthy family, but he is not from a poor one, either: my family have been prominent, well-to-do people in this middle-western city for three generations. the carraways are something of a clan and we have a tradition that we're descended from the dukes of buccleuch, but the actual founder of my line was my grandfather's brother who came here in fifty-one, sent a substitute to the civil war and started the wholesale hardware business that my father carries on today. ( ) nick says that the family tradition is that they descend from a line of scottish peers, a detail that he mentions with irony but that, at the same time, he did not need to mention at all. he has pride in his origins, his status and distinction, which he downplays and is wry about, but which matters to him. the carraways were immigrants, generations ago; they are not newly arrived on east coast shores. this is more than a family; in an american context, with its more compressed time-frame, it is a clan, a line. the founder of this family-line must have achieved a measure of success, his american dream, because when the civil war threatened him, he had the money to buy an exemption from service in the union army. he paid a substitute to risk mutilation or death in his place. after the war, nick was restless and, unlike the pioneers who journeyed westward, he moved in the opposite direction: i decided to go east and learn the bond business. everybody i knew was in the bond business so i supposed it could support one more single man. all my aunts and uncles talked it over as if they were choosing a prep-school for me and finally said, 'why ye-es' with very grave, hesitant faces. father agreed to finance me for a year and after various delays i came east, permanently, i thought, in the spring of twenty-two. ( ) nick is somewhat cavalier about turning to the bond business. he is not single-minded or ambitious, not motivated by a burning dream of his own. the fact that everybody he knew was in the bond business tells us about the types of people he and his supportive family are familiar with. nick then headed east, with a propitious advantage not available to others: his father agreed to finance him for a year. periodically, nick refers to the work he does, the people with whom he interacts, and his attitude toward them: i knew the other clerks and young bond-salesmen by their first names and lunched with them in dark crowded restaurants on little pig sausages and mashed potatoes and coffee. i even had a short affair with a girl who lived in jersey city and worked in the accounting department, but her brother began throwing mean looks in my direction so when she went on her vacation in july i let it blow quietly away. ( ) we hear nick's distaste as he reports that he consorted with clerks. he had a sexual affair; we do not know anything about it or even the girl's name-she is only a "girl," not a woman. her brother suspected that nick would take sexual advantage of his sister and then would dispense with her. nick's blithe tone of voice implies that indeed he would do something like this. to him, this young woman was merely a fling. nick adds that he "took dinner usually at the yale club," an experience he says he did not enjoy. but, nonetheless, he is a member of this club. further on, nick says that jay gatsby, then james gatz, had begun his studies at "the small lutheran college of st. olaf in southern minnesota," but had left it after just two weeks ( ). it is not only the very wealthy tom buchanan who benefits from privilege, but so does the ivy league graduate and yale club member nick. later, nick says: "the next april [ ] daisy had her little girl and they went to france for a year. i saw them one spring in cannes and later in deauville and then they came back to chicago to settle down" ( ). nick has the means to travel abroad and sojourn in resort towns on the french riviera and in normandy. he is among the fortunate few. nick's family, then, is prominent and well-to-do. tom's family is hugely rich; daisy's family has social standing and money. as for gatsby, born in north dakota: "his parents were shiftless and unsuccessful farm people-his imagination had never really accepted them as his parents at all" ( ). perhaps this is the trait in gatsby that for fitzgerald defines him as an american dreamer-imagination. it is imagination and tenacity, even ruthlessness, the willingness not only to move beyond one's origins but also to deny them. the greatest american dreamers say yes, but their power comes first from saying no. this is the insight that fitzgerald, writing during and about the s, establishes and explores. the american dreamer, as exemplified in the charismatic, crazy gatsby, strives for success, for self-realization, rushing forward. but this dream is propelled by the dreamer's disavowal of his or her past, the refusal to be that person: i cannot accept these parents, this upbringing. who i am, is intolerable to me, and i will not endure my existence in this paltry life: i will become someone else. when fitzgerald in the s was describing gatsby's dream, what were the conditions of american life that he witnessed? what was happening all around him? in the aftermath of the war, the u.s. economy in - had tumbled into a depression, especially in agriculture; the price of wheat plummeted by %, and cotton by %. the unemployment rate hit . % in . but, in a spectacular turnaround, it dropped to . % by the following year and was down to . % by . during the s, the gross domestic product (gdp) increased by %; annual per capita income did also, rising by %. as the scholar robert a. divine has noted: "the american people by the s enjoyed the highest standard of living of any nation on earth." propelled by commerce, industry, banking, and the stock market, the economy boomed from t at a growth rate of % per year. the u.s. accounted for nearly % of the world's industrial output. many americans at last had discretionary income, and, from shrewd marketers, they were receiving nonstop guidance about how to spend it. the historians george b. tindall & david e. shi explain: "more people than ever before had the money and leisure to taste of the affluent society, and a growing advertising industry fueled its appetites. by the mid- s, advertising had become both a major enterprise with a volume of $ . billion [$ billion today] and a major institution of social control." during the spending sprees of the s, americans could purchase cameras, wrist-watches, washing machines, and much else. from to , the number of telephones doubledthe word "telephone" occurs nineteen times in the great gatsby; the number of radios increased from , to million. by , " million people a week went to the moviesthe equivalent of half the nation's population" (steven mintz and randy roberts, hollywood's america, th ed., ). nick and tom attended yale. gatsby spent some weeks at oxford. daisy, meanwhile: we hear nothing about her education (which may have been entirely at home, with tutors). she has no interests other than travel and conspicuous consumption and display. the action of the novel takes place in ; the th amendment, giving women the right to vote, was ratified in august . there is no indication that this means anything to daisy. during the s,women began to benefit from greater freedom. divorce, for example, became easier. in , in every marriages ended in divorce; in , it was in . as the historian irwin unger has noted, in a typical woman's outfit consumed . yards of cloth; in , it required only seven yards. the ever-increasing popularity of movies and magazines also led to more attention to the right and best types of female behavior and appearance. as another historian, jane bailey, has said: by , hemlines were raised to below the knee; long curls gave way to short "bobbed" haircuts. pleasureseeking "flappers" (an english term once applied to prostitutes) drank, danced, and smoked their way through life. the heightened emphasis on female sexuality was not entirely emancipatory, however. as movies and magazines became more popular, standardized ideals of physical attractiveness took root. sales of cosmetics increased from $ million in to $ million in , as the goal of achieving perpetual youthfulness underwrote a cult of beauty and consumption. flappers' rejection of curves led to women binding their breasts and dieting to look boyish. the bathroom scale first appeared on the scene in the s, and cigarette ads targeted women with such slogans as "reach for a lucky instead of a sweet." daisy is slender, and she smokes. she also drinks alcohol, though, it seems, not to excess. this is in contrast to jordan baker's account of daisy's drunken state on the evening before her marriage to tom. too late, gatsby notified her that he was returning to the united states; by then committed to tom, she became "drunk as a monkey" ( ). this, in the story, was in june . prohibition went into effect in : it was illegal to manufacture, transport, or sell alcoholic beverages, and the consumption of alcohol, overall, declined. but drinking was common, and fashionable, for the middle and upper classes; at the expensive plaza hotel, tom takes out a bottle of whiskey, and daisy offers to make him a mint julep ( ). robert a. divine points out that "bootleggers annually took in nearly $ billion [$ . billion today], about two percent of the gross national product." gatsby is a bootlegger, a criminal: that is how he has amassed his fortune, supplemented by shady financial dealings with the gambler and gangster meyer wolfsheim. the s also marked the boom of the automobile-industry. henry ford had said: "i am going to democratize the automobile. when i'm through everybody will be able to afford one, and just about everyone will have one." when ford's model t was introduced in the early s, its cost was $ ; in , the cost of the model a, which replaced the model t, was $ . by , there were million registered passenger vehicles. automobiles abound in fitzgerald's book, and gatsby's car is the aristocrat among them, a radiant vehicle known to all: i'd seen it. everybody had seen it. it was a rich cream color, bright with nickel, swollen here and there in its monstrous length with triumphant hatboxes and supperboxes and tool boxes, and terraced with a labyrinth of windshields that mirrored a dozen suns. sitting down behind many layers of glass in a sort of green leather conservatory we started to town. ( ) tom and daisy have showy cars-and a chauffeur drives her to the tea at nick's where she meets gatsby ( ). meanwhile, the ineffectual gas-station man george wilson dreams that tom will bestow on him a car that the wealthy buchanans intend to get rid of; he appeals to tom, reminds him, and in response tom barks at him in annoyance. a monument to s' opulence and excess, there is, furthermore, gatsby's prodigious house, to the right of nick's place: "the one on my right was a colossal affair by any standard-it was a factual imitation of some hôtel de ville in normandy, with a tower on one side, spanking new under a thin beard of raw ivy, and a marble swimming pool and more than forty acres of lawn and garden" ( ). nick also visits the buchanan residence: their house was even more elaborate than i expected, a cheerful red and white georgian colonial mansion overlooking the bay. the lawn started at the beach and ran toward the front door for a quarter of a mile, jumping over sun-dials and brick walks and burning gardens-finally when it reached the house drifting up the side in bright vines as though from the momentum of its run. the front was broken by a line of french windows, glowing now with reflected gold, and wide open to the warm windy afternoon, and tom buchanan in riding clothes was standing with his legs apart on the front porch. ( ) fitzgerald foregrounds tom's truculent, conquest-seeking sexuality. later, we learn that he and daisy left chicago for this massive mansion in the east because of one of his sexual escapades ( ). the lifestyles of the rich and famous are maintained by innumerable workers-drivers, cooks, waiters, gardeners, servants. fitzgerald makes this crucial point often, as here, about gatsby's elaborate parties: "every friday five crates of oranges and lemons arrived from a fruiterer in new yorkevery monday these same oranges and lemons left his back door in a pyramid of pulp-less halves. there was a machine in the kitchen which could extract the juice of two hundred oranges in half an hour, if a little button was pressed two hundred times by a butler's thumb" ( - ). the butler, dehumanized, depersonalized, has been reduced to a thumb. gatsby does not give him a thought. this mansion-owner with the midas touch pays no more heed to his staff's mindnumbing routines than do the buchanans. fitzgerald perceived that the s economy was making american a new gilded age. at the beginning of the decade, president warren g. harding's principal cabinet member was secretary of the treasury andrew w. mellon, who cut personal income taxes to a maximum rate of %, lowered the estate tax, and repealed the gift tax. he also implemented steep tariffs and slashed federal spending. loyalists of big business were appointed to regulatory boards and agencies. corporate profits and stock dividends soared, rising far more rapidly than did the wages of workers. speaking in during his presidential campaign, herbert hoover declared: "we in america today are nearer to the financial triumph over poverty than ever before in the history of our land. the poor man is vanishing from us. under the republican system, our industrial output has increased as never before, and our wages have grown steadily in buying power." poor people were vanishing because no one was bothering to look for them. workers were losing power, and labor unions-a force during the era of eugene v. debs and the socialists and international workers of the world-suffered a falling off in their ranks. the historians tindall and shi point out: "prosperity, propaganda, welfare capitalism [i.e., bonuses, pensions, health and recreational activities in the workplace], and active hostility, combined to cause union membership to drop from about million in to . million in ." farmers had to deal with unstable prices, deep debts, foreclosures, and bankruptcies. farm exports fell as agriculture in europe was restored after the war; farm income in was billion; in , billion. what about african americans? nick refers to them several times, e.g., "as we crossed blackwell's island a limousine passed us, driven by a white chauffeur, in which sat three modish negroes, two bucks and a girl. i laughed aloud as the yolks of their eyeballs rolled toward us in haughty rivalry" ( ). in s new york city, few african americans were being escorted in limousines with white men as their drivers. most were sharecroppers in the south, under the sway of white landowners. falling prices for crops hurt them badly, and for many the s were harsh and unforgiving. hundreds of thousands of sharecroppers and other workers lost their jobs during this decade. many african-americans in the south migrated northward to new york, chicago, detroit, and other cities. they found employment but of an uneven and inadequate kind. much of the work they did was in the lowest-paying jobs; and they lived in segregated areas, in inferior-quality housing. as for other groups: a report on the condition of native americans found that half owned less than $ and that percent lived on less than $ a year. mexican americans, too, had failed to share in the prosperity. during the s, each year , mexicans migrated to the united states. most lived in conditions of extreme poverty. in los angeles the infant mortality rate was five times higher than the rate for anglos, and most homes lacked toilets. a survey found that a substantial number of mexican americans had virtually no meat or fresh vegetables in their diet; percent said that they could not afford to give their children milk. (digital american history, university of houston) by , the top % of the population owned % of all personal wealth. the top % owned %. only the top percent owned stocks. this was a decade of extreme income inequality, as fitzgerald confirms. there are the old money buchanans, the new money gatsby, the bond-businessman nick who is subsidized by his father; and then, on the other hand, there is the floundering, beaten-down george wilson, and, among many others alongside or lower down from him, the "finn" who works in nick's house as a maid-he never refers to her by name. in , economists concluded that a family of four needed $ per year [$ , today] for its basic necessities. even during this prosperous period, approximately % of american families did not reach this level of income. "the top . percent of american families in had an aggregate income equal to that of the bottom percent" (robert s. mcelvaine, the great depression, ) . also in , the stock market crashed, from in september to in july . banks failed; farmers lost their lands; factories and mines came to a stop. investments and savings were wiped out. farm income fell by %. foreign trade fell by %. by , personal income had declined by more than %. unemployment was %. in the automobile industry, production by fell to % of the total; the number of automobile workers fell to % of the total. by - , the average family income had collapsed to $ per year. there was no safety net. for much of the nation, financial prosperity and security were not achievable in the s, and by the s, except for the very fortunate, it had disappeared. so much for the american dream. but we should inquire into this american dream even more, this term to which the great gatsby is always linked. for it was in circulation not only during the s, but earlier as well. i have not been able to locate any book that has "american dream" in its title in the date range to . from to the present, by contrast, there are more than one hundred. still, the phrase does appear in various texts in the late th and early th centuries, and the implication is that people know what it means. a notable example is in an editorial in the montgomery advertiser, february , , urging the nation to be militantly ready and prepared for war: "if the american idea, the american hope, the american dream, and the structures which americans have erected, are not worth fighting for to maintain and protect, they were not worth fighting for to establish." zelda sayre was born in montgomery, alabama, in ; her father, anthony dickinson sayre ( - ), a lawyer, jurist, and democratic legislator, was appointed in to the state supreme court. i am sure that he read the montgomery advertiser; possibly he perused this editorial on a day when his daughter was at the breakfast table or in the living room with him. f. scott fitzgerald, commissioned as a second lieutenant, met zelda in montgomery in july ; this is altered slightly, but not significantly, in the novel-gatsby meets daisy in august , in louisville, kentucky. fitzgerald hence could feel the fervor of gatsby's dream because he had felt it strongly in himself. he craved success as a writer because through it he believed he could win zelda. his first novel, this side of paradise, was published on march , ; one week later, he and zelda were married. age twenty-four, fitzgerald had obtained the object that had enchanted him. by the early s, literary critics and scholars were regularly invoking "the american dream" in relation to the great soc gatsby, as did, for instance, marius bewley: "critics of scott fitzgerald tend to agree that the great gatsby is somehow a commentary on that elusive phrase, the american dream. the assumption seems to be that fitzgerald approved." to the contrary, says bewley: "the great gatsby offers some of the severest and closest criticism of the american dream that our literature affords…. the theme of gatsby is the withering of the american dream" ("scott fitzgerald's criticism of america," sewanee review, spring ). the american dream as aspiration and illusion had gained currency in the aftermath of world war ii and from the surge in the economy that boosted consumption in the s. the economy grew during this decade by %, and the median american family experienced an increase in purchasing power of %. unemployment was low, inflation was low. the critic sarah churchwell says: "it is not a coincidence that the great gatsby began to be widely hailed as a masterpiece in america during the s, as the american dream took hold once more, and the nation was once again absorbed in chasing the green light of economic and material success" (careless people: murder, mayhem, and the invention of the great gatsby, ). yet bewley refers to "withering," implying that the dream, as portrayed by fitzgerald, had in some earlier era flowered and flourished but had now shriveled and wizened. when was this era? the american dream was not widespread in the s, and it became even more restricted during the great depression decade. if there is a single main source for the term, it is james truslow adams's the epic of america, published in , six years after the great gatsby, and two years into the great depression, the high times for the fortunate in the s shattered. adams , born in brooklyn, was an excellent student in high school and college, but he faltered in his graduate studies in philosophy and history and found little satisfaction in publishing and finance. while living in new york with his father and sister, adams began to devote his time and energy to the writing of history, based in primary sources, rendered in an appealing, accessible style. adams's three-volume survey of the settlement of new england and its history to was a major success, and for this project and other books in the s he was widely praised. adams based the epic of america on his conviction that self-improvement and self-formation were the motive forces in american history. adams maintains that there has always been: … the american dream, that dream of a land in which life should be better and richer and fuller for every man, with opportunity for each according to his ability or achievement. it is a difficult dream for the european upper-classes to interpret adequately, and too many of us ourselves have grown weary and mistrustful of it. (adams's italics) he continues: "it is not a dream of motor cars and high wages merely, but a dream of a social order in which each man and each woman shall be able to attain to the fullest stature of which they are innately capable, and be recognized by others for what they are, regardless of the fortuitous circumstances of birth or position." adams states that the american dream is more than money and materialism: no, the american dream that has lured tens of millions of all nations to our shores in the past century has not been a dream of merely material plenty, though that has doubtless counted heavily. it has been much more than that. it has been a dream of being able to grow to fullest development as man and woman, unhampered by the barriers which had slowly been erected in older civilizations, unrepressed by social orders which had developed for the benefit of classes rather than for the simple human being of any and every class. and that dream has been realized more fully in actual life here than anywhere else, though very imperfectly even among ourselves. it has been a magnificent epic and dream, adams affirms. but he then asks, what about the american dream at present and in the future? if the american dream is to come true and to abide with us, it will, at bottom, depend on the people themselves. if we are to achieve a richer and fuller life for all, they have got to know what such an achievement implies. in a modern industrial state, an economic base is essential for all. we point with pride to our "national income," but the nation is only an aggregate of individual men and women, and when we turn from the single figure of total income to the incomes of individuals, we find a very marked injustice in its distribution. the concern that adams expresses is about income inequality-he saw it in the s, and again in the great depression decade. in this same year, , looking backward, fitzgerald wrote in an essay, "echoes of the jazz age": it ended two years ago, because the utter confidence which was its essential prop received an enormous jolt, and it didn't take long for the flimsy structure to settle earthward. and after two years the jazz age seems as far away as the days before the war. it was borrowed time anyhow-the whole upper tenth of a nation living with the insouciance of grand dukes and the casualness of chorus girls. but the moralizing is easy now and it was pleasant to be in one's twenties in such a certain and unworried time. the upper tenth troubles adams too, as he declares in a verdict that applies to the s, the s-and to where we are in the twenty-first century: there is no reason why wealth, which is a social product, should not be more equitably controlled and distributed in the interests of society. a system that steadily increases the gulf between the ordinary man and the super-rich, that permits the resources of society to be gathered into personal fortunes that afford their owners millions of income a year, with only the chance that here and there a few may be moved to confer some of their surplus upon the public in ways chosen wholly by themselves, is assuredly a wasteful and unjust system. it is, perhaps, as inimical as anything could be to the american dream. nick says about the very rich american dreamer gatsby: "he wanted nothing less of daisy than that she should go to tom and say: 'i never loved you'. after she had obliterated four years with that sentence they could decide upon the more practical measures to be taken" ( ). gatsby wanted money, an immense amount of it, which he procures by lawless means, so that he can capture daisy, who represents for him privilege and status. "obliterate": to remove utterly from recognition or memory; to remove from existence; to destroy utterly all trace, indication, or significance. it never occurs to gatsby to consider whether daisy, herself, wants to participate in his dream. he assumes that she does-and that she will immediately erase the fact that she has been and is married to tom and is the mother of a child. gatsby is blinded by his dream, and by money and the potency he believes that it gives him. at one point, in front of nick and jordan baker, daisy "got up and went over to gatsby and pulled his face down, kissing him on the mouth." she murmurs: "you know i love you" ( ). but for gatsby this will not suffice. he will not allow daisy to say that she once loved tom but now loves him. he commands her to negate the person she was, a person with a past and a memory of it. the money that gatsby has, and the magnitude of his hyperbolic purchases, should prove to her, so gatsby presumes, that he loves her and that she should join him in the story-line of their lives than he has constructed. gatsby does feel apprehension when daisy seems not to be falling into exact conformity with his image of her, to which nick replies: "i wouldn't ask too much of her," i ventured. "you can't repeat the past." "can't repeat the past?" he cried incredulously. "why of course you can!" he looked around him wildly, as if the past were lurking here in the shadow of his house, just out of reach of his hand. "i'm going to fix everything just the way it was before," he said, nodding determinedly. "she'll see." ( ) nick warns gatsby about the impossibility of this ultimatum, this imposition on daisy. but nick does not formulate his point in quite the correct terms-and gatsby does not discern the misleading nature of both nick's words and his own incredulous reply. gatsby does not want to "repeat" the past. his intention is not that at all. it is through money and rhetoric to obliterate the past, to write a new history on a blank page, as though the one there before had never existed. why not? if you have the money, you can do anything. fixing everything the way it was before: this links gatsby to meyer wolfsheim, who "fixed the world series" in ( ). it is criminal to recreate another person in the coercive manner that gatsby is committed to. fitzgerald intends for us to recognize that for gatsby "the way it was before" is not his dream. his dream is to make it the way it was not: he hates his past, and his money is his guarantee that he can dispense with the person he was and invite-that is, order-daisy to do the same. nick breaks from this dialogue to reflect on gatsby's obsession: "he talked a lot about the past and i gathered that he wanted to recover something, some idea of himself perhaps, that had gone into loving daisy. his life had been confused and disordered since then, but if he could once return to a certain starting place and go over it all slowly, he could find out what that thing was..." ( ; fitzgerald's ellipsis). nick's story is entwined with gatsby's. often it is difficult to know when nick is giving us an accurate impression of gatsby and when he is speculating about him. nick next proceeds to stage and paint the scene of gatsby's remembered vision of his momentous time with daisy: …one autumn night, five years before, they had been walking down the street when the leaves were falling, and they came to a place where there were no trees and the sidewalk was white with moonlight. they stopped here and turned toward each other. now it was a cool night with that mysterious excitement in it which comes at the two changes of the year. the quiet lights in the houses were humming out into the darkness and there was a stir and bustle among the stars. out of the corner of his eye gatsby saw that the blocks of the sidewalk really formed a ladder and mounted to a secret place above the trees-he could climb to it, if he climbed alone, and once there he could suck on the pap of life, gulp down the incomparable milk of wonder. ( ; fitzgerald's ellipsis) fitzgerald heightens nick's language, imbuing it with romance, melodrama, and phantasmagoric sublimity. this is far beyond anything that gatsby could articulate. it is sumptuous and strained, lavish and ridiculous: nick is appalled and seduced by the wealth-laden gatsby's effort to incarnate his daisy-inspired imagination. fitzgerald returns to this scene when nick once more tells the reader about gatsby's first experiences of daisy. he says that gatsby said: "she was the first 'nice' girl he had ever known. in various unrevealed capacities he had come in contact with such people but always with indiscernible barbed wire between. he found her excitingly desirable" ( ). an acute phrase: the "barbed wire" visible yet indiscernible, not to be seen. it is oracular for gatsby, who would take part in the argonne offensive in france ( ), one of the deadliest battles in u.s. military history, where there were labyrinthine networks of barbed wire in the killing zones. to pre-war gatsby, daisy is not only desirable but excitingly so: she arouses, stirs, stimulates him. she amplifies desire: "he went to her house, at first with other officers from camp taylor, then alone. it amazed him-he had never been in such a beautiful house before. but what gave it an air of breathless intensity was that daisy lived there-it was as casual a thing to her as his tent out at camp was to him" ( ). there is more here about the house than about daisy; it is not her, but the house to which gatsby (according to nick) attached the word "beautiful." this is where daisy lives, but the antecedent for "it" is "house"-that is, while daisy is special, it is the house itself that has "breathless intensity": "there was a ripe mystery about it, a hint of bedrooms upstairs more beautiful and cool than other bedrooms, of gay and radiant activities taking place through its corridors and of romances that were not musty and laid away already in lavender but fresh and breathing and redolent of this year's shining motor cars and of dances whose flowers were scarcely withered" ( ). nothing about daisy's appearance, not anything directly about her at all. the word "beautiful" reappears, but again not in reference to her but to the house. nick then returns to daisy: "it excited him too that many men had already loved daisy-it increased her value in his eyes. he felt their presence all about the house, pervading the air with the shades and echoes of still vibrant emotions' ( ). later, gatsby will insist that daisy obliterate, wipe out ( , ), her relationship with tom. but at this initial stage, her value to gatsby is increased because other young men have loved her. they confirm the rightness of gatsby's desire for her, intensifying it. the next passage takes us to the climax of gatsby's pursuit: but he knew that he was in daisy's house by a colossal accident. however glorious might be his future as jay gatsby, he was at present a penniless young man without a past, and at any moment the invisible cloak of his uniform might slip from his shoulders. so he made the most of his time. he took what he could get, ravenously and unscrupulously-eventually he took daisy one still october night, took her because he had no real right to touch her hand. ( ) gatsby is pretending to daisy to be someone he is not. in army uniform-another marvel, the cloak that is invisibleall of the officers are the same. gatsby can represent himself to daisy as better in status than he really is. deceiving her, he is playing a role; he knows (she does not know) who he is-the offspring of shiftless, unsuccessful parents whom he has repudiated. what makes the passage shocking is that, having deceived daisy, gatsby "takes" her sexually. he takes her, he took her; two lines later fitzgerald repeats, "he had certainly taken her." nick's account makes this sexual consummation not a loving one but an assault, a molestation, or worse. "ravenously" implies extreme hunger, being famished, voracious like a beast, intensely eager for gratification or satisfaction. "unscrupulously": without scruples, without conscience, unprincipled. is this love? if it is, it is expressed as if it were theft, a trespass, an act of resentment, of hate and self-hatred. fitzgerald could have written the passage differently, or not included it at all. this is what he wanted. when gatsby, his "taking" done, separates from daisy, "she vanished into her rich house, into her rich, full life leaving gatsby-nothing. he felt married to her, that was all" ( ). he feels married to her: it is hard to know what this means. for the main impression is one of coercion and grievance, of sexual violation. gatsby desires daisy. or, should we say that he despises her?-despises the socially privileged and wealthy? gatsby knows that daisy does not know who he is and would rebuff him if she did. his interaction with her has left him feeling cancelled out, null and void. "when they met again," says nick: two days later it was gatsby who was breathless, who was somehow betrayed. her porch was bright with the bought luxury of star-shine; the wicker of the settee squeaked fashionably as she turned toward him and he kissed her curious and lovely mouth. she had caught a cold and it made her voice huskier and more charming than ever and gatsby was overwhelmingly aware of the youth and mystery that wealth imprisons and preserves, of the freshness of many clothes and of daisy, gleaming like silver, safe and proud above the hot struggles of the poor. ( ) ( ) gatsby, objectifying daisy, values her silvery presence for its distance from futile poverty where dreams never come true. she is preserved in her wealth; she is imprisoned too, but the implication is that gatsby, by uniting himself to her, will liberate her along with himself. this is an impossible dream, as somewhere in his mind gatsby is aware. daisy is captivating but sullied in his eyes: he has tainted her by taking her. in a startling juxtaposition, fitzgerald passes from nick's description to gatsby's own colloquial speech: "i can't describe to you how surprised i was to find out i loved her, old sport. i even hoped for a while that she'd throw me over, but she didn't, because she was in love with me too. she thought i knew a lot because i knew different things from her.... well, there i was, way off my ambitions, getting deeper in love every minute, and all of a sudden i didn't care. what was the use of doing great things if i could have a better time telling her what i was going to do?" ( ) gatsby is acknowledging that, for him, the american dream is better talked about than experienced: he could have done great things but what is even better is the prospect of telling daisy that he will do them in the future. it might be better for gatsby never to do them, because if they were done, it would no longer be possible to talk about them, anticipate them, look forward to them. gatsby may realize that if he did great things, these would not make him happy. not doing them means not being disappointed. in the screenplay for his film adaptation of the great gatsby, , baz luhrmann revises the dialogue of this scene. gatsby says: "i knew it was a great mistake for a man like me to fall in love. a great mistake. i'm only …. i might still be a great man if i could only forget that i once lost daisy. but my life, old sport, my life has got to be like this…he draws a slanting line from the lawn to the stars." luhrmann is bringing out, putting into words, an insight into gatsby that fitzgerald glances at. gatsby reveals that he knows the mistake he made; in two senses, it is a "great" mistake. there is time for him to choose a different direction. money is not everything and neither is daisy, but gatsby cannot make this choice: he cannot forget that he lost daisy. does he want to possess her because he desires her, or does he desire her because he lost her? fitzgerald's exposition of, and inquiry into, the american dream, undertaken in , is psychologically complex, written in a suspenseful first-person form full of twists and turns, flash-forwards and flash-backs. fitzgerald criticizes delusion and illusion, yet from first to final page, his craftsmanship, his adroit literary language, is subtle and sensitive. he pays tribute to the american dream that he discredits, and we remain wedded to it. on the campaign train in iowa, , barack obama celebrated the american dream: as i've traveled around iowa and the rest of the country these last nine months, i haven't been struck by our differences-i've been impressed by the values and hopes that we share. in big cities and small towns; among men and women; young and old; black, white, and brown-americans share a faith in simple dreams. a job with wages that can support a family. health care that we can count on and afford. a retirement that is dignified and secure. education and opportunity for our kids. common hopes. american dreams. obama said that he, his grandparents, and other family members had achieved this dream, but that many americans were now finding their hopes for it to be unfulfilled: "while some have prospered beyond imagination in this global economy, middle-class americans-as well as those working hard to become middle class-are seeing the american dream slip further and further away." "you know it from your own lives," obama continued: americans are working harder for less and paying more for health care and college. for most folks, one income isn't enough to raise a family and send your kids to college. sometimes, two incomes aren't enough. it's harder to save. it's harder to retire. you're doing your part, you're meeting your responsibilities, but it always seems like you're treading water or falling behind. and as i see this every day on the campaign trail, i'm reminded of how unlikely it is that the dreams of my family could be realized today. obama told his audience-this was the basis for his campaign: "i don't accept this future. we need to reclaim the american dream." during his two terms, - , how well did president obama perform in his effort to restore and reanimate the american dream? in a study published in late , emmanuel saez and gabriel zucman concluded: "the share of wealth held by the top . percent of families is now almost as high as in the late s, when the great gatsby defined an era that rested on the inherited fortunes of the robber barons of the gilded age." they noted: the flip side of these trends at the top of the wealth ladder is the erosion of wealth among the middle class and the poor…. the growing indebtedness of most americans is the main reason behind the erosion of the wealth share of the bottom percent of families. many middle class families own homes and have pensions, but too many of these families also have much higher mortgages to repay and much higher consumer credit and student loans to service than before. ("exploding wealth inequality in the united states," washington center for equitable growth, october , ) preparing in for her presidential campaign, hillary clinton said: "we have to do a better job of getting our economy growing again and producing results and renewing the american dream so americans feel they have a stake in the future and that the economy and political system is not stacked against them." she had served as obama's secretary of state from to ; her promise to renew the american dream thus amounted to a critique of the administration that she had been part of. from - to - , hillary and bill clinton made more than $ million in lecture fees; in total, during these fifteen years after he left the white house, they made $ million. they led (and continue to lead) luxurious lives; they have a charitable foundation worth many millions; and their net worth (estimates vary) is somewhere in the $ million range. money "has always been passed down in families"-as fitzgerald shows through tom buchanan-"but today, across america, parents who can are helping their grown children in unprecedented ways" (jen doll, harper's bazaar, february , ). since , the clintons' daughter chelsea has served as a member of the corporate board of iac/interactivecorp, a media and investment company: she has received $ million in compensation. she has one qualification for this position: her parents. her wedding in cost $ million; for their new york city condo, she and her husband paid $ . million; they have a net worth in excess of $ million. hillary clinton lost the election in to donald trump, net worth, $ . billion, who had launched his campaign in june with a speech that concluded: trump: sadly, the american dream is dead. audience member: bring it back. trump: but if i get elected president i will bring it back bigger and better and stronger than ever before, and we will make america great again. during president trump's term, from forward, the numbers for growth, employment, and the stock market have been positive. vice president mike pence said, april , , that the american dream was "dying until president donald trump was inaugurated" in . trump's policies are generating jobs "at the fastest pace of all," pence emphasized, and this "gives evidence of the fact that the american dream is coming back." "was the american dream in trouble? you bet," pence said in an interview: "i really do believe that's why the american people chose a president whose family lived the american dream and was willing to go in and fight to make the american dream available for every american" (cnbc, april , ). donald trump jr. has said: "for the last years our biggest net export has been the american dream, but because of donald trump we've brought that american dream home, where it belongs" (june , ). eric trump, the second of the president's sons, echoes this claim: "we have achieved something that was incredible and something that is so much bigger than what we are and it shows that the american dream is alive and under him i think the american dream is going to be stronger than it was ever before" (fox business, september , ). on the other hand: in late , the census bureau reported: "the gap between the richest and the poorest u.s. households is now the largest it has been in the past years." "the most troubling thing about the new report," states the economist william m. rodgers iii, is that it "clearly illustrates the inability of the current economic expansion, the longest on record, to lessen inequality" (bill chappell, "u.s. income inequality worsens, widening to a new gap," npr, september , ). as for the record-setting stock market: in , % of americans owned stock; in , % do. this means that nearly half of the nation owns no stock-no mutual funds, no retirement funds. the top % of families with the highest income own, on average, $ , in stocks. among low-income workers, % of them do not have a retirement account or cannot afford to contribute to one. (allison schrager, quartz, september , ; gallup news, september , .) the authors of a report published in conclude: we live in an age of astonishing inequality. income and wealth disparities in the united states have risen to heights not seen since the gilded age and are among the highest in the developed world. median wages for u.s. workers have stagnated for nearly fifty years. fewer and fewer younger americans can expect to do better than their parents. racial disparities in wealth and well-being remain stubbornly persistent. in , life expectancy in the united states declined for the third year in a row, and the allocation of healthcare looks both inefficient and unfair. advances in automation and digitization threaten even greater labor market disruptions in the years ahead. ("forum on economics after neoliberalism," boston review, february , ) nevertheless, we dream on. in orlando, florida, june , , president trump announced his bid for reelection: our country is now thriving, prospering and booming. and frankly, it's soaring to incredible new heights. our economy is the envy of the world, perhaps the greatest economy we've had in the history of our country. and as long as you keep this team in place, we have a tremendous way to go. our future has never ever looked brighter or sharper. the fact is, the american dream is back, it's bigger and better, and stronger than ever, before. in , % of american workers made less than $ per hour. this places their income for the year below the federal poverty level. overall, "the number of people earning less than $ , accounts for . percent of the population." during the next five years, the job most in-demand, which will rise %, is home health-aide. its median salary is $ , . the reporter/journalist jeanna smialek observes that "unequal access to opportunities is now a global story. barriers vary by country, but children are generally more likely to earn incomes similar to their parents' in nations with higher income inequality." she comments further: "the graph of this relationship is often called a great gatsby curve, named after f. scott fitzgerald's novel about social mobility and its costs." the united states is "further toward the high-inequality, highimmobility end of the scale than other advanced economies." in the united states, says smialek, "higher incomeinequality goes hand in hand with lower upward-mobility," and she cites research by the economists raj chetty, nathaniel hendren, and others. hendren observes: "it just speaks to this kind of question: to what extent are we a country where kids have a notion of the american dream?" (bloomberg business week, march , ; see also john jerrim and lindsey macmillan, "income inequality, intergenerational mobility, and the great gatsby curve: is education the key?," social forces, december ). senator bernie sanders has spoken about the american dream. in , on the senate floor, he asked, "what happened to the american dream?", and he replied, "we are now the most unequal society" among all of the industrial nations. in his campaign for the nomination, sanders emphasized the crisis of income inequality, and he is emphasizing it even more. the son of jewish immigrants, a member of a family that struggled to pay the bills, sanders through hard work and education made it all the way to the u.s. senate; he now is "attempting to identify his own personal story with the american dream", a dream that, he contends, fewer and fewer americans can hope to achieve (walter g. moss, la progressive, march , ). on his campaign www-site, joe biden also presents himself as an embodiment of and proponent for the american dream: during my adolescent and college years, men and women were changing the country-martin luther king, jr., john f. kennedy, robert kennedy-and i was swept up in their eloquence, their conviction, the sheer size of their improbable dreams…. america is an idea that goes back to our founding principle that all men are created equal. it's an idea that's stronger than any army, bigger than any ocean, more powerful than any dictator. it gives hope to the most desperate people on earth. it instills in every single person in this country the belief that no matter where they start in life, there's nothing they can't achieve if they work at it. so too does senator elizabeth warren, and she has a proposal for reducing the inequality gap: i've got plans to put the american dream within reach for america's families-and a plan to pay for it with a two-cent wealth tax. a two-cent tax on fortunes of more than $ millionthe wealthiest . %can bring in the revenue we need to invest in universal child-care, public education, universal tuition-free public college and student debt cancellation for % of people who have it…. education was my ticket to live my dreams, and it's time we make that opportunity available to every family who wants it. (concord monitor, november , ) those at the top, the wealthiest americans: they are the most alarmed critics of the sanders and warren positions and proposals. hedge-fund manager leon cooperman, for instance, wailed about warren's intention to set new rules for wall street: "this is the fucking american dream she is shitting on" (politico, october , ). more temperately, he said: "let's elevate the dialogue and find ways to keep this a land of opportunity where hard work, talent, and luck are rewarded and everyone gets a fair shot at realizing the american dream." cooperman's net worth is $ . billion. critics of a tax increase on the very rich and of regulation that might lessen income inequality: these worried voices include michael bloomberg (net worth, $ . billion) and jeff bezos (net worth in , $ . billion; in , net worth, $ billion-the remainder after his wife received $ billion in their divorce settlement). the sports merchandise executive michael rubin (net worth, $ . billion) contends that boosting taxes on the super-rich "would have the exact opposite effect of what you want to happen…. what makes america great is that this is a true land for the entrepreneur…. what would happen is that people won't start businesses here anymore" (yahoo finance, january , ). mark cuban (net worth, $ . billion) weighs in: "i love entrepreneurship because that's what makes this country grow. and if i can help companies grow, i'm setting the foundation for future generations. it sends the message that the american dream is alive and well" (cnbc, march , ) . cuban endorsed hillary clinton in as the best advocate of (his phrase) "the american dream." she says that she is in favor of an estate tax, but as for a tax increase aimed at the very wealthy (like herself), she asserts that this would be "incredibly disruptive" (daily beast, july , ; business insider, november , ) . in , the world's wealthiest people added $ . trillion to their fortunes, increasing their collective net worth %, to at least $ . trillion. the twenty-six people at the top possess greater wealth than the . billion people in the bottom half of the world's population. in the united states, there are + billionaires. in a report, january , oxfam focused on this vast disparity and concluded: "extreme wealth is a sign of a failing system. governments must take steps to radically reduce the gap between the rich and the rest of society and prioritize the well-being of all citizens over unsustainable growth and profit." in the same month, many of the attendees at the world economic forum, "the most concentrated gathering of wealth and power on the planet," at their meeting in davos, switzerland, expressed a similar concern. kristalina georgieva, managing director of the international monetary fund, said: "the beginning of this decade has been eerily reminiscent of the s." in a report that was prepared for this meeting, the united states is at # in the world's social mobility index, behind, e.g., germany, france, canada, japan, and the united kingdom. one observer remarked: "canadians have a better shot at the american dream than americans do." (chloe taylor, cnbc, january , ; heather long, washington post, january , ; hanna ziady, cnn business, january , .) among americans, % say that there "is too much economic inequality." for young people, ages to , the figure rises to more than %. if there is a surprise in the polling, it is that only + percent say that reversing income inequality should be a "top priority." but the priorities they do emphasize, such as "creating affordable health care, fighting drug addiction, making college more affordable, fixing the federal budget deficit, and solving climate change"-all of these are connected to economic policy. people recognize this-which is why nearly % believe that the very wealthy should pay more in taxes (cnbc, january , ; npr, january , ). economists have demonstrated that inequality is higher today than it has been since the s, the decade of the great gatsby. in forbes magazine, for example, jesse colombo writes: "it's not fashionable to wear flapper dresses and do the charleston, but s-style wealth inequality is definitely back in style. america's ultra-rich haven't held as much of the country's wealth since the jazz age" (february , ). here are the conclusions presented in recent studies of the american dream: absolute mobility has declined sharply in america over the past half-century primarily because of the growth in inequality. socio-economic outcomes reflect socio-economic origins to an extent that is difficult to reconcile with talk of opportunity. your circumstances at birth-specifically, what your parents do for a living-are an even bigger factor in how far you get in life than we have previously realized. at least since the s, american have worried that the united states is no longer the "land of opportunity" it once was. data show a slow, steady decline in the probability of moving up…. millennials might be the first american generation to experience as much downward mobility as upward mobility. if fitzgerald were alive, he would see that the inequality he had depicted in the great gatsby has widened, that it is not a gap, but an abyss. all of this is true and crucially pertinent to fitzgerald's novel as we read it now. but he is saying even more in it, and here we need to move through and beyond american themes and the statistics that bear witness to them. for there is in the great gatsby a vision that exceeds money, inequality, and the american dream. i am referring in particular to the novel's final pages, to the elegiac, plaintive paragraphs that are familiar to many of us but that perhaps we have not really read. in them, fitzgerald is simultaneously american and global, national and international; he is transhistorical, universal. "these concluding lines are so impassioned and impressive," says the critic richard chase, "that we feel the whole book has been driving toward this moment of ecstatic contemplation, this final moment of transcendence" (the american novel and its tradition, ) . in the completed first draft, these lines are not at the end but, rather, at the close of the first chapter. fitzgerald made many revisions throughout his typed draft and page proofs. but he made very few changes in these paragraphs. what he did, was to relocate them. he wanted them to be the conclusion even as he knew that their melancholy intensity would be present in the mood and atmosphere of his story from the start. the mansion is empty. gatsby is dead and buried. soon nick will be leaving for the midwest: most of the big shore places were closed now and there were hardly any lights except the shadowy, moving glow of a ferryboat across the sound. and as the moon rose higher the inessential houses began to melt away until gradually i became aware of the old island here that flowered once for dutch sailors' eyes-a fresh, green breast of the new world. its vanished trees, the trees that had made way for gatsby's house, had once pandered in whispers to the last and greatest of all human dreams; for a transitory enchanted moment man must have held his breath in the presence of this continent, compelled into an aesthetic contemplation he neither understood nor desired, face to face for the last time in history with something commensurate to his capacity for wonder. ( ) these sentences are laden with loss and longing. but this is only one register of it, the tone of voice of the first-person narrator nick. fitzgerald's perspective is here as well, and he is more tough-minded in his judgments. the term "pandered" points us, ironically and critically, toward nick, toward the role he played in fostering gatsby's quest for daisy that culminated in the dreamer's death. nick's imagination expands as he moves centuries backward in time to the moment when long island was dense with forests and when dutch sailors first glimpsed it. for them, according to nick, it might have been the breath-taking prospect of a new beginning, an eden rediscovered, and he seems to share in this reverie. but fitzgerald knows that history was more complicated then, and that much has transpired since. in april , henry hudson, an english sea captain hired by the dutch east india company, undertook a voyage of exploration to north america to locate a sea and trade route to asia. by july, his eighty-foot ship with its crew of sixteen had reached nova scotia and shortly thereafter he arrived at present-day staten and long islands, and then travelled up the river that now bears his name. hudson grasped that here were lucrative possibilities for commerce, for money-making, for profit, especially in the fur trade. settlers began to arrive in - ; the first group consisted of thirty families. this dutch territory included manhattan, parts of long island, connecticut, and new jersey. in , peter minuit, director of the colony, with a payment of blankets, kettles, and knives, secured an alliance or treaty with the neighboring native americans. the dutch settlement was small, some people, in the midst of tribes that were sometimes in conflict with one another. relations between settlers and native americans were, at the outset, peaceful for the most part, but there was an attack on a dutch fort at albany, named fort orange, as early as .; bloody conflicts broke out in the s and into the s. the new netherland population was , with in new amsterdam at the southern tip of manhattan. also in , a dutch ship unloaded eleven slaves in new amsterdam, and others were brought up the coast from the caribbean. new amsterdam was built by slave labor, and by , one-third of the population was african. nick imagines dutch seamen looking from the outside in, but fitzgerald wants us also to be cognizant of the view from the inside out-nick himself is on the shore, looking outward. the enchantment, the awe, may have been thrilling for those on the outside who first experienced it, but in this novel filled with people of various races and ethnicities, fitzgerald presents a history that these men aboard ship did not know, did not possess but would inaugurate and sustain through dispossession, enslavement, battle, and war. fitzgerald calls attention to the deforestation of the land, the assault on it, the exploitation of it as it lay there ready to be taken. nick refers to the "fresh, green breast of the new world," an image that fitzgerald is connecting to the green light, beguiling and perilous, and to the terrible death of myrtle wilson, killed by daisy driving the car with gatsby next to her: the "death car" as the newspapers called it, didn't stop; it came out of the gathering darkness, wavered tragically for a moment and then disappeared around the next bend. michaelis wasn't even sure of its color-he told the first policeman that it was light green. the other car, the one going toward new york, came to rest a hundred yards beyond, and its driver hurried back to where myrtle wilson, her life violently extinguished, knelt in the road and mingled her thick, dark blood with the dust. michaelis and this man reached her first but when they had torn open her shirtwaist still damp with perspiration, they saw that her left breast was swinging loose like a flap and there was no need to listen for the heart beneath. the mouth was wide open and ripped at the corners as though she had choked a little in giving up the tremendous vitality she had stored so long. ( ) nick then says: and as i sat there brooding on the old, unknown world, i thought of gatsby's wonder when he first picked out the green light at the end of daisy's dock. he had come a long way to this blue lawn and his dream must have seemed so close that he could hardly fail to grasp it. he did not know that it was already behind him, somewhere back in that vast obscurity beyond the city, where the dark fields of the republic rolled on under the night. he broods his way into a final affirmation and tragic prophecy: gatsby believed in the green light, the orgastic future that year by year recedes before us. it eluded us then, but that's no matter-tomorrow we will run faster, stretch out our arms farther.... and one fine morning--so we beat on, boats against the current, borne back ceaselessly into the past. when we read the great gatsby, we inevitably think (as fitzgerald wants us to) about the american dream-what it was and is, and whether, if we are losing this dream, we might restore it in this twenty-first century riven by income inequality. but when we really read the great gatsby, we realize that fitzgerald has written both a great american novel and a great novel for the world. the great gatsby belongs with melville's moby-dick, dreiser's sister carrie, and ellison's invisible man-milestone american books that readers everywhere deeply respond to. fitzgerald compels all of his readers to reflect on what it means to be human, bodies ensnared by time, consumed by desires destined never to be fulfilled. the great gatsby is rooted in a time and place and nation: it is american through and through, and it is an essential guide to and diagnosis of the way we live now. but it is, furthermore, a literary work with an all-inclusive address that speaks to societies and cultures outside its american context. fitzgerald has a message about life in america and a message about life itself. he believes that life for all persons is the pursuit of happiness, not the achievement of it. most of us have faith in, we yearn for, a future of maximum well-being-not just a good life, but one so good that it overcomes and redeems, or seems to, the inexorability of death. this is the dream we cannot reach, a satisfaction that cannot be measured, a happiness that eludes us. if only, somehow, we could get to it, we would know immortality. we tell ourselves that we need to try harder and desire more intensely. then it will come. but it does not, and the "current" pulls us rearward, into oblivion. there is no religious comfort or consolation. we beat on, striving, not finding contentment. this is the only choice we have: amid a finite existence, we seek persons and objects that beckon to us, that we are convinced represent desires and dreams uniquely our own. the great gatsby is superior by far to everything that fitzgerald wrote before it, and nothing that he wrote after it, not tender is the night ( ) or the love of the last tycoon, comes close to it. everything that fitzgerald had, everything that he was, is in this novel. his self-destructive behavior, alcoholism, financial pressures, and the mental illness of his wife zelda denied him the luminous career that his astonishing talent seemed to promise. he died of a heart attack in december , age forty-four. in a letter in october to his daughter scottie, fitzgerald described to her "the wise and tragic sense of life": by this i mean the thing that lies behind all great careers, from shakespeare's to abraham lincoln's, and as far back as there are books to read-the sense that life is essentially a cheat and its conditions are those of defeat, and that the redeeming things are not "happiness and pleasure" but the deeper satisfactions that come out of struggle. having learned this in theory from the lives and conclusions of great men, you can get a hell of a lot more enjoyment out of whatever bright things come your way. the great gatsby dramatizes the myths and realities of this country and continent from the moment of the settlers' arrival and then onward to the s and to the present where we see the american dream broken by income inequality. but what may be even more remarkable is that, translated into fifty languages worldwide, the great gatsby transcends its national origin and setting. fitzgerald tells truths about the human condition, about desire, disappointment, and death. really read, it is about the american dream and much more. june : the pandemic that struck the united states and the world earlier this year has caused widespread illness and death, damaged the national and international economies, and created agonized uncertainty about the future. scholars and researchers are in agreement about one point at least: the pandemic has caused (and will continue to cause) the most harm among america's most vulnerable-the elderly, minorities, and low-income workers and their families. many have painted a bleak picture. alexis crow, for example, an expert in economics and finance, has noted: in the united states, the twinned health and economic crises resulting from coronavirus have laid bare several persistent issues in the socio-economic fabric of the country-and which also complicate the trajectory of sustainable growth for future generations. these issues include fiscal sustainability and ballooning deficits; income inequality and the vast disparity in livelihoods across the income distribution; the hollowing out of the mittelstand (small and medium enterprises); and the future of work and employment. (atlantic council, may , ) a report from the international monetary fund expresses a similar concern: the pandemic will leave the poor further disadvan-taged…. the inequality gap between rich and poor has widened after previous epidemics-and covid- will be no different…. if past pandemics are any guide, the toll on poorer and vulnerable segments of society will be several times worse. indeed, a recent poll of top economists found that the vast majority felt the covid- pandemic will worsen inequality, in part through its disproportionate impact on low-skilled workers. (world economic forum, may , ) the epidemiologist sandro galea, in his study of the national and international effects of coronavirus, has said: discussions about covid- pandemic's effects tend to focus either on public health or the economy, as if they were two separate matters. but they are linked, and not just by data about the disease's disproportionate impact on poor and minority populations. the worldwide economic devastation from lockdown policies is sending millions into povertyincreasing their exposure to potential covid- infection as well as to the deadly threat that comes simply from being poor. a central determinant of health is money-the ability to afford such basic resources as nutritious food, access to good medical care, safe housing, quality education, and the simple peace of mind that comes with having the means to weather sudden shocks…. less money generally means shorter, sicker lives, as reflected by the approximately -year gap in life expectancy between the richest and poorest americans. (washington post, may , ) david n. cicilline, a member of congress from rhode island, links the sickness and mortality rates of covid- to income inequality, and to the deterioration of the american dream: the global pandemic has laid bare the economic fragility of millions of american families. in the last few decades, the american middle class has been hollowed out. for millions of americans living paycheck to paycheck, the american dream-the ideal that in this country anything is possible, and everyone can achieve the security of a good life-is nearly unattainable. for decades, anyone taking a clear-eyed look into the economic well-being of our middle class would have seen the warning signs. but this public health crisis has uncovered an even deeper, more fundamental crisis for all to see. the united states is simply no longer the country of opportunity that we once were. (boston globe, may , ) in the midst of the pandemic, the nation also has been racked and torn apart by the death of george floyd, an african-american killed by white police-officer derek chauvin (three of his fellow officers assisted in the arrest) in minneapolis, minnesota, on may th. demonstrations and protests have taken place throughout the united states and abroad, with angry voices demanding action to bring an end to police brutality, systemic racism, poverty, income inequality, and the lack of equity in education and health care. many have spoken with extreme bitterness and indignation. kari winter, an american studies scholar and minneapolis-native, contends-and others have reiterated this indictment: when derek chauvin pressed his knee on george floyd's neck, he committed a brutal, horrific murder. he had three immediate collaborators, but they are not alone in their guilt. their behavior is enabled by the systemic rot of racism. four hundred years of white supremacy have put the american dream of democracy on life support…. when black lives don't matter, none of our lives matter. when black rights don't matter, the american constitution does not matter. freedom of the press? arrested. cruel and unusual punishment? celebrated. right to be secure in your person and house against unreasonable search, seizure or murder? smashed to smithereens. (university of buffalo news center, june , ; see also robin wright, "fury at america and its values spreads globally," the new yorker, june , ) in the great gatsby, with brilliant perception and understanding, fitzgerald examines and exposes the limitations of the american dream. it might crack and come apart in the years ahead in ways that would shock but not surprise him. this is the brutal end of the line for myrtle, a dreamer whose "tremendous vitality" links her to gatsby, possessed by the "colossal vitality" of the desire he stored so long for daisy. the great gatsby brims with violence. we hear about the civil war, the great war, race-war (tom buchanan's panic that "nordics" soon will be overwhelmed by "the colored empires key: cord- - vd d authors: hinchman, angelica; ali, diab; goodwin, bailey w.; gillie, monica; boudreaux, jacob; laborde, yvens title: global health is local health: a multidisciplinary perspective of covid- date: journal: ochsner j doi: . /toj. . sha: doc_id: cord_uid: vd d nan in december , the novel coronavirus-severe acute respiratory syndrome coronavirus (sars-cov- )-likely originated from a wet animal wholesale market in wuhan, china. originating from hospitalizations for respiratory illness in the hubei province on december , , infections quickly erupted to confirmed cases by january , in provinces throughout china and to , cases by january , . [ ] [ ] [ ] the affordability and availability of modern travel, crowded airports, and the recycled air of planes aided in unprecedented geographic reach and rapid escalation of viral transmission. globalization, in combination with the prolonged incubation of covid- , its lengthy survival time on surfaces, and the extended period of viral shedding in infected persons, enhanced the virus's largely undetected proliferation. by january , additional cases were reported beyond china's borders in taiwan, thailand, vietnam, malaysia, nepal, sri lanka, cambodia, japan, singapore, south korea, united arab emirates, united states, philippines, india, australia, canada, finland, france, and germany. the virus spread beyond local and national borders. what was previously a vague and distant global health problem quickly became a local public health concern everywhere. by the end of march , new orleans, la, had emerged as the city with the highest fatality rate per capita in the united states. this fatality rate disproportionately affected african americans who accounted for % of coronavirus deaths in louisiana, while making up only % of the state's population. the heavy burden of noncommunicable disease in louisiana, compounded by recent social events in the city of new orleans, including the carnival season, catalyzed the rapid transmission of sars-cov- throughout the state. in this paper, we review the multidisciplinary impacts of the covid- pandemic across the healthcare system. from a local focus on new orleans to a global perspective, we relate how rapidly changing healthcare policy, evolving use of technology, and social media dynamics played roles in perception and response to the pandemic. we reflect on the perspectives of evolving national health policy, public health demands, impact on mental health, strain on primary and emergency care, and the emergence of telehealth on a global and local scale. the rapid escalation from the outbreak in wuhan, hubei province, china, to global pandemic in a matter of days presented a challenge for the coordination of a federal public health response in the united states. the federal government's response during the early days after the world health organization alert on december , consisted of evacuating american diplomats from wuhan, banning air travel from china, and preparing to repatriate americans from abroad while managing stirring fears at home ( figure ). [ ] [ ] [ ] the government's facilitation of communication between healthcare experts and the public during an emerging pandemic amplified an existing challenge in public health: finding a balance between informing the public of imminent health threats while preventing increased anxiety and panic in response to elevated risk perceptions. as us government officials struggled to keep up with the rapidly evolving data on covid- , a disjointed public health policy response resulted, leading to public distrust, panic, and polarized perceptions of the disease. as in china, delays in information sharing and guidelines by the us government created a window of uncertainty, providing the opportunity for social media platforms to assert themselves as primary news sources for the american people, resulting in rumors and misinformation being spread within the united states via social media posts and the sharing of obscure news outlets. , content-shaping algorithms that personalize the user experience, popular on websites such as facebook, compounded the cycling of misinformation, enabling public confusion, anxiety, and mistrust of the government. one outcome was the panic buying of toilet paper, hand sanitizer, antimicrobial wipes, and other goods during the early days of the covid- outbreak. [ ] [ ] [ ] public confusion was amplified by inconsistent information shared by us government representatives. on march , president trump announced a national -day policy of social distancing. six days later, the president tweeted that social distancing may be "worse than the problem itself." on april , although the president echoed recommendations by the us centers for disease control and prevention (cdc) for americans to don cloth face coverings while in public, he emphasized that these recommendations were temporary and voluntary and stated that he would not wear a mask himself. such communications led to the emergence of competing narratives surrounding how people should best protect themselves and others from the virus based on a patchwork of guideline interpretations. the contradictory information from government officials demonstrated the importance of having coordinated public health policy information and responses. the majority of covid- confirmed cases appeared to occur in patients to years of age ( . %), but the population group with the highest mortality are those ࣙ years old. preliminary findings from the china cdc show a positive correlation between age and fatality ( figure ). among , cases, confirmed covid- positive patients ࣙ years of age had a . % mortality rate. age is not the only contributing factor for increased mortality; preexisting comorbidities including hypertension, diabetes, cardiovascular disease, chronic respiratory disease, and all types of cancer increase the risk of fatality compared to having no comorbid conditions at all. however, these factors are not mutually exclusive as older patients are more likely to have one or more comorbid conditions. the state of louisiana is particularly at risk given the prevalence of comorbidities in the population. in the most recent census ( ), louisiana ranked th in overall health outcomes based on behavior, policy, clinical care, community, and environment ( figure ). in reports focused on particular conditions, % of adults were reported as having hypertension, . % with diabetes, . % with chronic obstructive pulmonary disease, and % with heart disease. [ ] [ ] [ ] [ ] the prevalence of these comorbid conditions makes the population of louisiana as a whole susceptible to poor health outcomes. in addition to the effect of comorbid conditions, preliminary data revealed race as a contributing factor in covid- cases and mortality. in louisiana as of early may, african americans accounted for approximately % of covid- associated fatalities ( figure ) . , statewide data showed that % of deaths occurred in orleans parish, where roughly % of the population is african american. , consolidated cdc data from states from the month of march showed that % of hospitalized, covid- -confirmed patients were black, while this group made up only % of the surrounding population. in new york city, both african american and hispanic covid- -related death rates outnumbered those of whites or asians. meanwhile, the american public media research lab independently began collecting racial breakdown data from the district of columbia and states and found alarming evidence of a % increased likelihood of covid- fatality among black patients compared to white, hispanic, or asian patients. an important note is that the collective data reporting on covid- are incomplete, as states are only reporting the racial breakdown on a portion of recorded deaths. this racial disparity is thought to be attributable to a combination of socioeconomic factors, including a long history of structural injustice and oppression in the united states that has resulted in social inequity, higher rates of chronic conditions, poverty, and unemployment among african americans. this sentiment is reflected in data demonstrating that african americans aged to years are twice more likely to die from heart disease, and, on average, develop heart disease at a younger age than white americans. this statistic is in addition to documented higher rates of hypertension, diabetes, cerebrovascular disease, asthma, and obesity in african american communities. furthermore, minority populations are more likely to work in the so-called essential labor sector as workers in healthcare, transportation, government, and food supply. one in african americans and in hispanics have a job that does not allow them to stay at home and social distance. , minority populations' ability to social distance is also impacted by the higher likelihood of living in multigenerational households and densely packed living situations. finally, african americans are more likely to report financial barriers to accessing healthcare. financial barriers may delay presentation, allowing case severity to advance and increasing the likelihood of intensive care unit (icu) admission. the racial bias, stereotyping, and prejudice known to affect quality of care by healthcare providers, as well as patient experience in the healthcare system, are also contributing factors. to further explore these racial and demographic disparities, more comprehensive research and data are needed to guide population-specific interventions and health policy. without these data, health officials and lawmakers will not be able to adequately address health inequities or understand the scope of the disparities. emergency departments (eds) and urgent care centers across the world are classically on the frontline of disaster and are where the first encounters with patients generally occur. as rumors mounted and anxiety built in the absence of communication from national leaders, eds were flooded by patients with covid- -related complaints, reaching a total of , , visits in the united states and peaking at , visits in week. with the influx of patients rushing to hospitals for care, resources were reallocated to address the dramatic increase in patient volume and to mitigate transmission within these facilities. healthcare institutions across the globe prioritized frontline emergency and intensive care departments to directly address mounting patient demands. resources, including personnel, were shuffled within systems, and elective and nonemergent procedures were canceled. these steps had the positive effects of distancing healthy patients from disease-laden hospitals, permitting the conversion of unused space to additional icu capacity, and conserving personal protective equipment (ppe), but the resource reallocation also left a void in the care of thousands of patients. as crowded waiting rooms devolved into vectors for viral spread with the surge of patient encounters, protective measures became necessary to decrease transmission among waiting patients. one hospital in taiwan implemented buffer areas to segregate patients based on risk. patients with fever and respiratory tract symptoms were categorized into high, intermediate, or undetermined risk groups and allocated to separate areas to minimize the potential spread of covid- throughout the hospital. patients were managed in these designated areas and transferred to isolation rooms for the collection of nasopharyngeal swabs. by establishing this protocol, the hospital was able to achieve a positive predictive value of . % for covid- infection in the high-risk area of the buffer zone. however, strategies such as these are hindered by time availability, lack of well-established protocols, and limited accessibility to ppe, further compounded by significant drops in ppe production in china. institutions compensated for the increase of patient needs by establishing call-in telephone lines to mitigate the brunt of public panic and minimize the burden on the ed. strategies evolved to keep healthier patients away from hospitals through the establishment of large-scale communication lines that encouraged home management of mild symptoms to limit transmission within healthcare institutions. ochsner health established a nurse-and medical studentrun call center to triage sick patients outside of the ed that eventually evolved into a platform for symptom monitoring of covid- -positive patients from home. integrating this call center into ochsner's covid- response plan enabled ongoing resource-sparing medical contact with a large patient population at one of the major hotspots for infection in the united states. despite the implementation of new hospital protocols in response to the covid- pandemic, the public's fear of waiting rooms as vectors for disease swelled, and ed attendance began to drop while the percentage of covid- associated illness continued to rise. noninfected patients began avoiding the ed out of fear of contracting the virus. as a result, care was delayed for some patients with potential health emergencies, further contributing to the escalating mortality observed in the united states. hospitals in other parts of the world have reported consequences of complex covid- protocols. a hospital in hong kong, china, has documented evidence of delayed primary percutaneous coronary intervention treatment of stsegment-elevation myocardial infarction, not only because of delays in seeking care but also because of institutional delays caused by new covid- safety protocols. although necessary to limit the transmission of disease, some emergency and triage adaptations have resulted in unforeseen consequences to patient care. new zealand and denmark had some of the earliest and most aggressive responses to the covid- pandemic. new zealand began mandatory quarantines for all visitors on march , one of the strictest policies in the world at the time, even though only cases had been documented nationwide. just days later, new zealand instituted a complete countrywide lockdown, including a moratorium on domestic travel. under these level restrictions, grocery stores, pharmacies, hospitals, and gas stations were the only commerce allowed; vehicle travel was restricted; and social interaction was limited to within households. denmark, which already has one of the world's highest functioning healthcare systems, had more than times as many beds with ventila-tors as it had patients hospitalized with critical covid- symptoms. additionally, because of the universal healthcare model in denmark, all treatment, including testing, was without cost to those who needed it. in contrast, the primary care system in the united states lacks a standardized healthcare unit. public and private outpatient practices vary in size and ownership, creating hurdles to identifying the problems covid- presented to primary care. the primary care collaborative (pcc) began conducting weekly surveys to try to identify the issues primary care workers were facing. on march , , the pcc published results from a survey of more than physicians, nurses, nurse practitioners, and physician assistants working in the primary care sector. survey responses indicated limited capacity for testing in the outpatient setting, which was compounded by the stress of addressing an abundance of patient concerns, challenges in limiting the exposure of healthy patients, and a shortage of ppe for both staff and patients. as the surveys continued in subsequent weeks, the stressors shifted to limiting routine visits and clinic staff absences because of illness or isolation. despite patients being receptive to telehealth visits, % of primary care workers who responded to the survey did not work at a practice that offered e-visits. interestingly, this number decreased to % by the next week, highlighting the rapid expansion of telehealth services. by week , more than , primary care workers from all states had responded to the survey, and the major issues impacting access to care were identified as disparities among racial minorities, patients with low income, and patients with no internet access. the adaptations to minimize in-person appointments created new challenges for treating patients with preexisting conditions and training patients and physicians in a new way of practicing medicine. the week survey showed that % of responders felt that patients avoiding or delaying care until after the pandemic will lead to non-covid- deaths, and % believed that patients will experience avoidable illness. in england, primary care physicians suspended routine checks for all patients > years nationwide. , similarly, primary care physicians in new orleans limited in-person visits and moved routine checks to telemedicine when possible. as a result, clinicians are having to learn new skills, platforms, and ways to care for patients. from a healthcare standpoint, pandemics cause a predictable surge in demand because of the infectious agent itself and because of the associated mass anxiety. the unfamiliar and mysterious nature of an invisible agent makes it seem "powerful, evil, and imperceptible." further, as misinformation rapidly spread, the pandemic had a profound behavioral impact, resulting in avoidance or anger, scapegoating, disruption of work-life balance, restricted activities, and substance use. factors such as the deaths of those seen as vulnerable, inadequate resources, paranoia, conspiracy theories, loss of faith in leaders and institutions, and the restriction of civil liberties all may have unforeseen impacts on downstream societal perception and social participation. , in new orleans, the compounded fears of infection, isolation, and quarantine, as well as resource shortages and scarcity, contributed to a heavy cognitive-emotional burden. vulnerable populations requiring additional mental health considerations include migrants and refugees, people with cognitive or mobility impairments, the disadvantaged and homeless, children and adolescents, pregnant and postpartum women, and people who depend on systems of care. people with preexisting psychiatric disorders, including those with addiction and substance abuse issues, are especially vulnerable, not only to the uncertainty associated with covid- but also to the potential to be more stigmatized and marginalized compared to their already problematic acceptance. at the end of march , market research by nielsen demonstrated a % increase in alcoholic beverage sales compared to the prior year, but only % of americans reported an increase in alcohol or substance use intake. , despite the predictable increase in the need for mental health support, resources were reallocated to support primary care and hospital settings to directly address covid- infection, leaving mental health services insufficiently prioritized in new orleans. the new orleans national alliance on mental illness (nami) chapter had to suspend all new patient intakes, psychosocial rehabilitation, community support, and education programs in the early stages of the pandemic with scarce virtual options to take their place. a few new orleans phone and virtual support groups have become available, including the #getyamindright virtual support group hosted by the institute of women & ethnic studies, the nami new orleans-associated survivors of suicide loss virtual support group, keep calm through covid crisis phone line providing mental health and substance abuse counseling services. however, these very few mental health resources adapted to address pandemic-relevant mental health may be underprepared for the compounding roles of providing specialized care to those with preexisting mental health disorders, substituting for preestablished community support groups, and handling pandemic-related psychiatric problems. both in new orleans and worldwide, substantial increases in anxiety and mood disorders, substance use, domestic violence, and child abuse appear to be likely as schools remain closed. the downstream effects of this mental health emergency are difficult to predict. telemedicine was initially developed as a tool to address resource-limited populations that lacked accessibility to healthcare centers. it has increasingly become a focus of research in all health sectors globally, with the original emphasis placed on its use in psychotherapy and mental health services. prior to the covid- pandemic, telehealth was not recognized or established as an integral part of the american healthcare system and was accessible to only slightly more than institutions across the country. since the beginning of the covid- pandemic, the needs for isolating patients, limiting exposure, providing medical maintenance, and delivering essential care have highlighted telemedicine as a critically important solution for healthcare delivery. in addition to conserving resources, providing virtual care through telemedicine allows physicians to assess infected patients and patients under investigation without risking exposure to the practitioner, support staff, and other patients. as the supply of ppe, medical staff, and hospital beds dwindled, the importance of effective, resourceconserving measures shined a spotlight on telemedicine. now, more than ever, the global need for resource-sparing healthcare options is reflected on the local level. the united states has been slow to incorporate telehealth into its healthcare systems, unlike other countries such as china. however, sudden demands for a platform that enabled social distancing-compliant healthcare access accelerated the adoption of telehealth in the united states. the covid- emergency declaration allowed for enactment of an waiver under the social security act to expand medicare coverage to patients seen by video visit for any purpose. the waiver also allows for the prescription via telepsychiatry service of schedule ii to v controlled substances that previously required an in-person visit, thus giving patients covered by medicare access to medications without the risk of physical exposure in the office. this waiver bypasses major barriers to care, including limitation of services, range of treatment, and state-specific restrictions in licensing that stunted previous government telemedicine incentives. however, a gap remains for those covered by private insurance or medicaid, for whom this waver does not apply to date. in new orleans, telemedicine programs were adapted to address the needs of the pandemic. patients in high-risk demographic groups were targeted specifically for remote visits so that they could avoid going into clinics and hospitals. the majority of these targeted patients had low socioeconomic status, high comorbidities, and low technology literacy, and they were older in age. while telehealth options circumvent classic socioeconomic barriers to care, such as transportation and financial restraints, new barriers such as the inability to be trained on and navigate the telemedicine system, lack of access to smart devices, and inadequate wireless internet connections are obstacles in converting to a virtual visit system. inequities to accessing telemedicine services will need to be addressed in future health policies. existing social factors-such as psychological, cultural, health, and socioeconomic status-collectively contribute to the public perception and interpretation of risk in a pandemic. pandemic communications must balance public engagement to optimize a unified capacity for citizens to practice precautions that reduce transmission while also minimizing panic. a article analyzing the role of uk twitter in regard to information sharing during the h n pandemic found that the largest category of information users interacted with were resource information tweets that shared links or were descriptive in nature. in this category, news sources had significantly more engagement than health authorities. news publications have the power to sway public perception through tone and recontextualization of the information being shared. early sharing of information from public health officials may establish health authorities as the primary resource regarding health information, reduce public speculation and distrust, moderate public paranoia and anxiety, and unify public involvement in health initiatives such as social isolation. increasing public health awareness by providing information and promoting guidelines could facilitate compliance with government mandates. one example is to develop a list of recommended items and suggested quantities for a -week quarantine per household. this public health promotion could be extended to grocery stores, with the recommendation to assemble kits of items to minimize shoppers' time in public settings. overall, a prompt and aggressive approach to information sharing by public health officials could ease public anxiety and enable an organized public response to improve health outcomes in a pandemic. the covid- pandemic has affected all healthcare practitioners, including students. medical students across the united states in their final years of schooling, primarily working in the clinical setting, had their studies suspended to minimize their exposure to the coronavirus. these alterations may have a lasting impact on their careers. removal from clinical settings, suspension of away rotations, and canceled board examinations left many third-and fourthyear students without the opportunity to meet the standard requirements of the national resident matching program to secure an intern placement for the next year. at the ochsner clinical school in new orleans, as at several other us medical schools, third-and fourth-year students refused to be sidelined. despite a -week suspension of studies that removed students from their clinical rotations, approximately students volunteered during their reallocated vacation time to assist in the response to the pandemic. students volunteered at call centers, contributed to the development of louisiana's first rapid testing center, and acted as family liaisons/advocates to take some of the load off of physicians and nurses who typically fill these roles, thereby allowing them to focus on direct patient care. the need for public mental health support has been critically demonstrated during the covid- pandemic, revealing weaknesses in both public and private healthcare systems and the need for improved mechanisms for basic care and refill/delivery of essential psychiatric medicines. mental illness, already a barrier to traditional care because of its nature, was exacerbated by the isolation, anxiety, and compounded stigmas of the pandemic. the literature supports using a system of stepped care in treatment that involves the universal offering of effective, resource-conservative treatment and then advancing care as necessary based on individual patient needs. given the capabilities of telehealth, virtual platforms could be used for psychiatric telehealth consults and group visits in resource-limited settings. even if these recommended changes are implemented, the healthcare system will likely remain insufficient unless community support is also strengthened. the social distancing measures of the covid- pandemic resulted in a lack of programs that provided community support, rehabilitation, and therapeutic services. in conjunction with comprehensive telehealth programs, social media could be used to connect people to evidence-based mental health resources and healthy practices. these platforms could also integrate check-in functions; promote collective resilience in the face of community stressors; and improve systems of mental health surveillance, reporting, and intervention for the anticipated increase in domestic violence and child abuse during the covid- pandemic. further, nontraditional groups could be trained to provide psychological first aid, reinforcing the public's ability to check in with one another and provide effective support. these nontraditional groups can include community populations that have been well documented in studies of task-shifting in the global mental health literature (teachers, religious leaders, barbers) or could be those involved in healthcare (medical students, medical assistants, pharmacists, physical therapists). training an expanded range of multidisciplinary healthcare team members in psychological first aid could also help address the mental health burden these providers have as vulnerable populations themselves. covid- illuminated the need for increased understanding of the impact of collective community stressors on healthcare workers, as well as programs dedicated to optimizing the mental health of providers susceptible to both direct and vicarious trauma. telemedicine rapidly expanded to meet the demand of the covid- pandemic. however, many obstacles to care still exist, including health access inequity. patients without smart devices or internet access are unable to receive comprehensive, virtual care. this inequity is compounded by lagging health policy that historically has and continues to funnel funding for telemedicine into medicare-specific programs. while the population covered by medicare will benefit from access to virtual visits, this policy leaves those with private insurance, those covered by medicaid, and uninsured patients out of the picture. barriers also include reimbursement restrictions, licensure, credentialing restrictions, and broadband internet connectivity. reimbursement and licens-ing restrictions have been temporarily suspended to allow greater telehealth access during the pandemic. this suspension highlights the need for sustainable change to increase access. the goal is to have telemedicine systems in place and health policies that support their use and availability so that a fully integrated and stable system is available, and patients are comfortable using it as a primary source of care. preexisting limitations of healthcare access were compounded during the covid- pandemic by recommendations to avoid eds and efforts to decrease outpatient visits for patients with noncommunicable diseases. despite the increased availability of telehealth services, patients without internet access or smart devices cannot access this mode of healthcare effectively. because of the racial inequity in covid- cases and mortality, the need to address socioeconomic disparities affecting covid- outcomes is clear, especially in new orleans and other cities where preliminary data support this imbalance. to understand the breadth of the issue, the compilation of comprehensive nationwide data on the racial and socioeconomic breakdown of cases, complications, and deaths is imperative. these data can help guide population-specific interventions and health policy in preparation for future epidemics. with the suspension of nonessential work in states by mid-april, millions of americans lost their jobs and health insurance. in some locations, % of individuals obtaining assistance from soup kitchens and food pantries had never visited one prior to the pandemic. delays in business reopenings may lead to long-term repercussions in health and access to healthcare. in early april, the estimated unemployment rate was % (the highest rate of unemployment since the great depression), and million americans had applied for unemployment in the prior weeks. reduced access to care because of economic hardship increases the risk of disease, as classically, people of lower socioeconomic status typically have worse health outcomes than those in higher socioeconomic brackets. while incentives to protect the economy, such as lifting shelter-in-place mandates, may seem protective by increasing health insurance coverage, lifting isolation measures prematurely may risk a second wave of infection similar to the one that occurred during the spanish flu epidemic and further deplete the primary care system. the decrease in access to healthcare is also attributable to physician and medical staff shortage. the covid- pandemic has amplified the stresses of global physician shortages. a report from the association of american medical colleges identified a shortfall of , to , physicians during the prior decade. older physicians are being called out of retirement, and medical students in their final year of study are accelerating their graduation to expand the workforce and aid in the increasing workload in response to the pandemic. as more healthcare workers are infected themselves, the population continues to age, and the ripple effects of covid- impact the health of our nation, the burden on the healthcare system will continue to grow. the need for more physicians is undeniable, and this need must be reflected in the number of available residency positions. facing such shortages, we cannot afford to turn away educated professionals seeking training. in anticipation of new orleans reopening, ochsner health, in conjunction with the city of new orleans, began the first phase of a study to assess the covid- disease burden in the greater new orleans area. nontraditional testing centers were established, including one at the new hope baptist church, to increase access to testing in communities where people lack transportation to travel to established testing sites. selected study participants were tested for covid- using both nasopharyngeal swabs and serum antibody tests. these data, combined with previously documented cases, will be used to gain insight into the extent of the spread of covid- prior to the reopening of the city. increasing the access to testing among underserved populations could facilitate quarantine measures and expedite connections to care prior to an escalation of symptoms. in addition, outreach programs are targeting african americans to help address healthcare disparities. the louisiana perinatal quality collaborative (lapqc) has a dedicated health equity task force focused on addressing health inequity associated with provider practice. the lapqc has implemented unit huddles that allocate time specifically for participating teams to discuss health equity in the context of covid- and create space for the discussion of ideas to minimize the impact of implicit bias in practice. ochsner medvantage clinics are creating healthcare access equity by removing financial barriers to care. these ochsner-based clinics work primarily with patients who are considered high risk for hospital readmission and for poor outcomes with covid- . as a result, services have been focused on supporting high-risk populations via telemedicine with waived copay fees. when normal operations resume, medvantage clinics will offer home visits and lyft health rides to patients who are unable to access transportation or who are physically unable to come to the clinic and will focus on addressing goals of care, including advance care planning. institutions and providers can take further action to tackle disparities in health by increasing awareness of implicit bias and how it can affect practice. using tools such as those provided by the government alliance on race and equity can help identify and address racialized health inequities. race-driven health disparities are prevalent throughout the american healthcare system and will require a unified response guided by comprehensive data to eliminate them. the word global in the term global health refers to the scope of current issues, not their location. global health problems are too often portrayed as the distant issues of others-until they reach our doorstep. globalization has made all populations vulnerable to disease, exploiting our interdependence with a clear predilection for the socioeconomically disadvantaged. innovative primary care solutions must address community inequity and the social determinants of health, clearly illustrated in louisiana where african americans account for the vastly disproportionate majority of covid- -associated cases and fatalities. solutions should not be limited to the pandemic response but necessitate adaptation from the clinical to political level. during the pandemic, men-tal health has been unprioritized despite a rapidly increasing need for resources and initiatives that support collective resilience, the minimization of stigma, and the feeling of social closeness while physically distant. the unstable and unsupported telemedicine infrastructure has been forced to expand without proper patient or healthcare provider training, understanding of outcomes, or systems in place for dissemination or optimization. this infrastructure must become an integrated, fluent system prepared for disaster response, while also optimized for routine use to combat current barriers in primary care. last, to aid in providing unified messages to government officials, systems must be developed to better synthesize medical knowledge among stakeholders. an increase in trained professionals is necessary, and the trained professionals and students at the crossroads of medicine, technology, economics, and diplomacy will be increasingly critical in the evolution of healthcare. the digital age of the st century has played a role in many of the devastating effects of covid- . yet technology has also provided and facilitated new tools, collaboration, and creativity for 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