Little is known about how the home environmental supports physical activity and screen media usage. The purpose of this study was to develop and test the reliability and validity of a self-report instrument to comprehensively reflect the availability and accessibility of physical activity and screen media equipment in the home environment.Ten families participated in the initial field testing to provide feedback for instrument development. Thirty one adult participants, each of whom had at least one child 10–17 years old, completed two Physical Activity and Media Inventory (PAMI) instruments. The first PAMI was completed simultaneously, but independently, with a research assistant to assess validity. A second PAMI was completed by the participant one week later to assess reliability.The adult participants were mostly mothers/female guardians, mean age 38 ± 7.2 years, mostly Caucasian (52%), college educated (65%), living in single family homes (74%). Test-retest reliability was acceptable to strong for all summary variables . For validation, reports from participants and research assistants were strongly correlated . Compared to participants, research assistants reported a greater percentage of physical activity equipment as "in plain view and easy to get to" and a smaller percentage of items as "put away and difficult to get to".Our results indicate strong evidence for the reliability and validity of the variables calculated from the PAMI. This self report inventory may be useful in assessing the availability of physical activity and screen media equipment in the home environment and could be used in conjunction with other home assessment tools  to identify obesogenic home environments. The use of ecological models to describe and understand physical activity and other health behaviors calls for new strategies for assessing and intervening upon the social and physical environments that affect those health behaviors . While mValid and reliable methods of assessing environmental supports for physical activity and competing sedentary media pursuits within the home environment are needed. Assessments of both the activity and sedentary environmental supports are warranted since physical activity and sedentary behavior are unique and independent behaviors ,7. A perTo date, most physical activity inventories have shown weak (r = 0.04 to 0.19)  or no asIn addition, previous home environment assessment tools have focused on availability, not accessibility. Accessibility is related to ease of use and cueing of behavior. A toy or piece of sports equipment that is readily available and easy to access poses a smaller barrier to use than one that must be retrieved from some inconvenient space. Likewise, the presence of a television set in the bedroom or a basketball hoop in the yard may serve as a visual cue to make use of those pieces of equipment. Similarly, stimulus control (i.e. controlling stimuli that can encourage or discourage a behavior) is recognized as one of the important processes of change used in conjunction with the Transtheoretical Model of behavior change  and has The purpose of this study was to develop and test the reliability and validity of a self-report survey instrument to comprehensively reflect the availability and accessibility of physical activity and media equipment in the home environment. It is our hope that such an instrument may help us better understand how the environment impacts the health and health behaviors of families.This research was conducted as part of the Identifying Determinants of Eating and Activity (IDEA) study for the purpose of designing and assessing the reliability and validity of an instrument to assess the home environment with regard to equipment related to physical activity and screen time. IDEA is an etiological study to evaluate potential determinants of the development of overweight and obesity in youth; it is being conducted in the metropolitan area of Minneapolis and St. Paul. IDEA assesses potential obesogenic factors in youth's personal, family, home, school, and neighborhood environments using a longitudinal cohort design .The PAMI was designed to be a self-report inventory of both the availability and accessibility of equipment and other resources that may support family members' participation in activity and sedentary behaviors. We were interested in creating an instrument that documented the physical environment, not individual behavior within the environment, therefore, we chose not to assess the frequency with which equipment inventoried was used.The development of the PAMI began by examining and adapting existing inventory instruments to address the specific needs of our research objectives and by creating a draft inventory. This measurement tool went through multiple drafts where face validity, clarity of the questions and format, and feasibility of administration was reviewed by study investigators and with other researchers who study family health. When a satisfactory draft was complete, we asked a convenience sample of ten families, recruited through local park and recreation centers, to complete and comment on the inventory. All participants were able to complete the PAMI and feedback suggested that the PAMI would be feasible as a self-report instrument. Based on their feedback, we further refined the instrument to improve instruction clarity and form layout; this version was used to assess the reliability and validity of the PAMI instrument.The PAMI version that was evaluated in this reliability/validity study included a list of 50 physical activity equipment items grouped by the following categories: sports equipment, fitness equipment, transportation equipment, foot wear, water sports, and outdoor/yard ,2. Number of channels received ,3. Number of videos and DVDs in the home ,4. Number of video and computer games in the home ,5. Type of internet service ,6. Size of the primary television in the home .Opposite the list of items there was a list of 16 rooms  which also included Yard/Outdoor Space, Attic/Basement/Storage Area, Garage, and Automobile(s) where respondents indicated the location of the available activity or media equipment. There was space for three "other" rooms in case the home had a room not listed  or more space was needed for a particular location (most common for the garage).To determine validity, one parent/guardian from each participating family completed the PAMI while a trained research assistant simultaneously completed an inventory in the family's home. To determine reliability, the same parent/guardian completed a second inventory one week after the first administration. The second inventory was done without the presence of a research assistant. All data were collected during May-June, 2006.Families were recruited to participate in this study through posted flyers and staffed information booths at four Minneapolis Park and Recreation Department buildings. Eligibility criteria included that each family had at least one child between the ages of 10 and 18 and an adult (parent/guardian) willing to complete the inventory and permit a home visit for validation purposes. Written informed consent was obtained prior to all data collection activities. The University of Minnesota Institutional Review Board approved this study.At the first visit, one adult household member and a research staff member did a walk through of the house, independently completing the PAMI instrument. The respondents were asked to walk through each room and indicate which physical activity and media equipment items were present (using code numbers from the list) and to rate the accessibility of each item. Access response options were: put away and difficult to get to; put away and easy to get to; in plain view and difficult to get to; in plain view and easy to get to. The research assistant independently completed the criterion PAMI at the same time with as little communication with the participating family member as possible. If a participant began speaking, the research assistant would ask them not to speak. Due to the potentially intrusive nature of such an inventory, the research assistant only inventoried those items that were in plain view, without moving or looking under furniture or opening closets, unless the participant did so first.At the end of the first visit, the research assistant left a blank PAMI instrument with the participant. The participant was asked to independently complete their second PAMI approximately one week later using the same approach as the first administration. A self-addressed stamped envelope was provided for mailing the completed form back to research staff. Reminder messages (telephone and email) were made to families one day prior to the day when the second inventory was to occur.Demographics were collected by self report during the first PAMI administration and included the age, race, and education level for each member of the household and one question asking about their homeowner status .The PAMI data were reduced to the following primary variables, calculated separately for physical activity and media equipment: total number of items, the density of items in the home , the number of items located in bedrooms, the density of items in bedrooms, the number of televisions in the home, and the number of televisions in bedrooms. For comparability to a checklist type of instrument ,13, whicWe also created and assessed two summary scores. First, we calculated separate summary scores that accounted for availability and accessibility of the physical activity equipment ) and media equipment (Media Availability and Accessibility Summary Score (MAASS)). Each item was multiplied by the accessibility code with 1 = "put away and difficult to get to" and 4 = "in plain view and easy to get to". A higher score reflects a greater overall presence in the home (both availability and accessibility).To provide more detail, we examined specific categories of items, including; sports equipment, fitness equipment, transportation equipment, water sports equipment, and outdoor/yard equipment). Within each of these categories, we calculated the total number of items and mean accessibility ratings for all items within each category.To rank the overall quality of the home, an overall home environment score was also calculated as the ratio of the PAASS to the MAASS (referred to as the Activity:Media Ratio Score). A higher overall Activity:Media Ratio Score would reflect a home more conducive for being physically active and less sedentary.SAS version 9.1  was used for all data analyses. A p ≤ 0.05 significance level was used as a guide for identifying significant relationships. Test-retest reliability of the continuous variables from the PAMI  was assessed by intraclass correlation coefficient . Test-retest of the accessibility ratings  was assessed by Mantel-Hanzel chi square analyses. The reliability of the additional media-related questions was assessed by percent agreement .Validity was evaluated by examining agreement between data from the participants and research assistants using Pearson correlation coefficients for continuous variables. Mean differences in continuous variables between the participant and the research assistant were identified with two-tailed independent t-tests. Comparison of the accessibility ratings between the participant and research assistant was calculated by Mantel-Hanzel chi square analyses.A total of 31 families agreed to participate in the study and data from all families are included in these analyses. All participating families completed the PAMI at least once for validation purposes, and over 77% also completed the PAMI a week later to assess reliability. The PAMI took, on average, 40 minutes to complete but was dependent on the size of the home and the number of items present.Table Table The test-retest reliability for the number of items within all physical activity equipment categories was high (ICC = 0.87 to 0.99) Table . ReliabiThe test-retest reliability for the additional media questions ranged from K = 0.42 (0.10 to 0.73) for the number of video and computer games to K = 1.00 for the type of television and for the type of internet service. The Kappa statistics for the number of videos/DVDs  and number of television channels  were both acceptable. The Kappa statistic for television size  is based on categorizing the responses into small (<25"), medium (25–39"), and large (> = 40").Table Table Reliability and validity were also assessed for the overall home environment Activity:Media Ratio Score (the ratio of the PAASS to MAASS). At Time 1 and 2 the Activity:Media Ratio Score was 8.3 ± 7.98 and 8.3 ± 7.28, respectively (ICC = 0.91 (0.81 to 0.96)). There was a strong association between the participant- and research assistant-derived home environment scores  and no significant difference in scores .This study assessed the test-retest reliability and validity of a self-administered, physical activity and media equipment inventory instrument for the home environment. Reliability ICCs for all of the physical activity and media equipment variables were moderate to high. This was true for all of the continuous variables, including the checklist quantity and the physical activity and media summary scores. When broken down by categories of physical activity items, reliability of the number of items remained consistently high across categories. The accessibility ratings were similar between the two administrations of the PAMI for fitness, transportation, and water sports equipment. In contrast, the accessibility ratings for sports and outdoor/yard equipment were different with fewer items considered "put away and difficult to get to" at the second administration, compared to the first. The reason for this difference may be a real change in where items in the home were placed or in the participants' perception about the accessibility of the items.Validity, as assessed by comparing the participant and research assistant data, was consistently high for all calculated variables for both physical activity and media equipment. The PAASS summary score was higher for the research assistants compared to the participants and likely reflects the research assistants recording more items as "in plain view and easy to get to" compared to the participants. When broken down by categories of physical activity equipment, validity coefficients for the number of items in each category were still generally high. The distribution of accessibility ratings for the media equipment were similar between participants and research assistants with most items being "in plain view and easy to get to". Research assistants, however, recorded a smaller percentage of physical activity items as "put away and difficult to get to" and a greater percentage of items as "in plain view and easy to get to" as compared with participants. The difference between participant and research assistant ratings of accessibility across all physical activity items seems to be driven by a difference in ratings for the sports and yard/outdoor equipment.There may have been a discrepancy between what participants and research assistants considered "put away". While the participant may consider items placed on the floor by the kitchen door as, "put away" , the research assistants would have coded such items as, "in plain view". The term "put away" did not necessitate that the items be in a box, cabinet, drawer, or other closed container. In addition, this discrepancy may have occurred due to the protocol followed by the research assistants which allowed them to only record items that they could see, without opening doors, closets and looking under furniture , unless the participant first did so. Our intention with implementing this protocol was to protect participant privacy. Further modification and testing of accessibility options is warranted given these findings.This was a small pilot study with several limitations. The majority of respondents were Caucasian, college educated and lived in single family homes. Additional validation studies are warranted in larger and more representative samples to determine the PAMI's psychometric properties in minority and lower income populations and those who live in apartments or condominiums. Participants were recruited from local parks and recreation departments which may have biased our sample by including relatively active families with relatively large amounts of physical activity equipment. Several families, however, had very few physical activity items, evidenced by the large standard deviations for most of the physical activity equipment variables. While the list of physical activity items was fairly comprehensive, some items may be more relevant in certain geographical areas . Therefore, the list of items may need to be modified based on the population being studied. Only screen based media items were included on the PAMI. A more comprehensive assessment of media sources in the home would need to include magazines, radios, portable music players, cell phones, and possibly other sources. During the validation visits, participants walked from room to room to complete the PAMI, as the instructions indicate. Whether this happened during the second administration of the PAMI, when the participants were by themselves, is not known. The PAMI is also not designed to assess how frequently or who in the home, is using the equipment. However, in an ecological model, characterizing the environment is an important end in and of itself as the environment is important in influencing behavioral choices. Lastly, data were collected in the spring and seasonality should be considered when interpreting the location and accessibility data since some items  may be moved and made very accessible during the winter but stored away at other times of the year.At present, it is not known if the PAMI is useful in characterizing homes along dimensions related to important health outcomes such as obesogeneity, levels of physical activity or sedentary behaviors. We also do not yet know if the PAMI is a useful instrument for showing change overtime as might be useful in intervention research that attempts to improve the healthfulness of the home environment. Future research will be needed to examine both the discriminant and predictive validity of the PAMI.In spite of these limitations, the PAMI is a potentially important addition to the field. The PAMI provides a more objective assessment of the presence of physical activity and media equipment items as compared to other research examining children's perception of adequate equipment ,11. The In the PAMI instrument tested here  were sometimes difficult for the participants to find and record. Therefore, for the main IDEA study, the PAMI has been expanded so that each room has its own page containing the list of items where the participant indicates how many of each item are present in that room and the associated accessibility. We believe the re-formatted version of the PAMI will be easier for participants to complete, although this newer version was not tested in this pilot study.The PAMI may be a useful tool for describing the physical home environment related to opportunities for physical activity, sedentary behaviors and possibly the obesogeneity of the home environment. The main IDEA study will assess the associations between PAMI variables, physical activity and sedentary behaviors, and weight status of both the adult and youth participating in the study. In addition, the longitudinal design of the IDEA study will allow us to look at physical activity and media equipment in the home environment as potential determinants of physical activity, sedentary behavior, and as factors related to the obesogeneity of home environments. In conclusion, the results from this study indicate that the variables calculated for this study  provide reliable estimates for describing the home environment related to the presence of physical activity and screen media equipment. The validity of the accessibility ratings for the physical activity items was less consistent and requires further investigation.JS and LL conceived the study. All authors  contributed significantly to the development of the inventory instrument and the study design, manuscript development and revision. All authors read and approved the final manuscript.The Physical Activity and Media Inventory (PAMI) instrument. The full PAMI instrument used for this study.Click here for file


A public health emergency, due to a novel influenza virus that affects humans, was declared by the WHO on April 25, 2009. On June 11, 2009, Dr. Margaret Chan, Director-General of the World Health Organization, raised the pandemic alert level to level 6 after the identification of swine-origin influenza virus (S-OIV) cases in more than one WHO region.[What will happen in the next months can be predicted from previous pandemics and their progress. Miller et al., elegantly describe signature features of four major pandemics of the nineteenth and twentieth centuries: the 1889 A/H1N, the 1918 A/H2N2, the 1957 A/H3N2, and the 1968 pandemics.[To date, there are more than 50,000 confirmed cases in more than 90 countries around the globe, with more than 230 deaths. In the kingdom of Saudi Arabia, 39 cases have been diagnosed, but no S-OIV-related deaths have occurred. Overall, cases continue to be mild, and death rates continue to be low.The challenges faced by policy makers are decisions regarding vaccine production as well as vaccine and medication purchases and distribution, all of which are critical and difficult. Many of these decisions must be based on virus evolution and disease severity, but this information is not fully available. FurthermThe Kingdom of Saudi Arabia has made additional preparations this year for the upcoming Hajj and Omra seasons by creating scientific committees under the direction of the Ministry of Health, to decide on proper precautionary measures to ensure a safe pilgrimage. These decisions are to be based on the present and evolving scientific evidence on the pandemic as it becomes available.Disease transmission can potentially occur through direct droplet nuclei or surface contamination with the virus from respiratory secretions. There is also the potential of feco-oral transmission, as fecal shedding is expected in patients with diarrhea.The full clinical spectrum and natural history of the disease is not yet determined. Most cases have thus far been mild and limited in severity. Patients at risk for severe and fatal disease are predicted to be those who are at risk for severe seasonal influenza. Of the confirmed cases of S-OIV reported in the USA, most presented as mild, uncomplicated, febrile respiratory illnesses. Among thHealthcare providers should obtain a nasopharyngeal swab from suspected cases of swine influenza, for testing. Protocols for specimen collection and transportation should be followed according to the guidelines of the local health department. In the Kingdom of Saudi Arabia, the local guidelines are provided by the Ministry of Health; these guidelines have been published and distributed to all health care facilities and are available on their website. ManagemeThere is now a clear identification of a pandemic due to a novel swine H1N1 influenza virus; this pandemic includes cases from the Kingdom of Saudi Arabia. The high number of cases in specific geographical regions may be explained by the focused epidemiological survey, where more cases could be identified if an enhanced global surveillance took place. For our local concern in the Kingdom, it is imperative that global surveillance continues and that poor countries, from which pilgrims originate, are included in such a surveillance. Such information would assist the Kingdom and the Muslim world in making informed decisions on the annual pilgrimage, for instance, vaccine prerequisites for obtaining a Hajj visa or the exclusion of certain countries from participating in the annual Hajj; which is an extreme measure that has not been taken yet. Finally, continuous surveillance of humans and animals affected by influenza viruses within the Kingdom has become a necessity and not a luxury.


An epidemic may exhibit different spatial patterns with a change in geographic scale, with each scale having different conduits and impediments to disease spread. Mapping disease at each of these scales often reveals different cluster patterns. This paper will consider this change of geographic scale in an analysis of yellow fever deaths for New Orleans in 1878. Global clustering for the whole city, will be followed by a focus on the French Quarter, then clusters of that area, and finally street-level patterns of a single cluster. The three-dimensional visualization capabilities of a GIS will be used as part of a cluster creation process that incorporates physical buildings in calculating mortality-to-mortality distance. Including nativity of the deceased will also capture cultural connection.Twenty-two yellow fever clusters were identified for the French Quarter. These generally mirror the results of other global cluster and density surfaces created for the entire epidemic in New Orleans. However, the addition of building-distance, and disease specific time frame between deaths reveal that disease spread contains a cultural component. Same nativity mortality clusters emerge in a similar time frame irrespective of proximity. Italian nativity mortalities were far more densely grouped than any of the other cohorts. A final examination of mortalities for one of the nativity clusters reveals that further sub-division is present, and that this pattern would only be revealed at this scale (street level) of investigation.Disease spread in an epidemic is complex resulting from a combination of geographic distance, geographic distance with specific connection to the built environment, disease-specific time frame between deaths, impediments such as herd immunity, and social or cultural connection. This research has shown that the importance of cultural connection may be more important than simple proximity, which in turn might mean traditional quarantine measures should be re-evaluated. The spatial pattern of disease cases in an epidemic, and the apparent process of diffusion, will vary dependent on the geographic scale of investigation. Although it is commonly accepted that such geographic variation exists, a lack of suitable epidemic data at the individual case level has proved limiting in visualizing these scale variations. This paper uses mortality data from the yellow fever epidemic of 1878 in New Orleans, with a focus on the French Quarter, to consider both variations in scale-dependent disease pattern, and the impact the built environment and culture plays in the formation of those patterns. The ability to investigate these last two aspects of the epidemic, both of which have previously been identified as important in understanding the nuances of disease spread [Flavivirus, family Togaviridae, its symptomology often including haemorrhaging and jaundice from which the disease gained its name [Aedes aegypti mosquitoes [Yellow fever is a virus of the genus its name . The majsquitoes . This isEmily B Souder. This steamboat had just arrived from disease-impacted Cuba. The Board of Health reports went on to describe how personal connections set on a backcloth of the built environment, which included named streets, residences and shared courtyards, helped to spread the disease from its point of origin. Although it is unlikely these diffusion patterns occurred exactly as described, individual buildings are likely to have played an important role in disease spread. Indeed, Carter [Although several yellow fever epidemics occurred in the southern United States during the 1800s, the most notable of which were in 1853 and 1878, a common pattern among them was an initial entry through a Gulf Coast city (most frequently New Orleans), followed by simultaneous diffusion patterns at different geographic scales ,5. By re, Carter  used mul, Carter -12.geographically interesting epidemic in the 1800s.Once the initial disease introduction had occurred into New Orleans, the subsequent diffusion process would involve multiple scales, and locations, as the disease ran through the city, while simultaneously spreading along transportation routes, especially the Mississippi River  with botThe 1878 epidemic also signalled a shift in the vulnerability of the young to the contagion. The common perception of the time that yellow fever was a "strangers disease" resulted from the apparent immunity of families native to New Orleans . The harOfficial Report of the Deaths from Yellow Fever as Reported by the New Orleans Board of Health (ORD from this point on), written in the following year, detailed the mortality role of the epidemic, listing the name, age, nativity, place of residence and date of death [The 1878 epidemic is suitable for a multiple-scale investigation because of the spatial richness of the mortality data. The of death ,20, mortof death . For thiA previous investigation of the ORD for the majority of New Orleans incorporated a spatial (50 m mosquito "flight range") and temporal sequence of disease deaths based on the extrinsic incubation period of the mosquito to identify a spatial variant of the basic reproduction number . This apThis paper, however, demonstrates that a GIS can be used to include both complex geography and cultural interconnectivity when mapping and analysing disease spread. Specifically this paper addresses two questions; are different spatial patterns of disease occurrence observable at different geographic scales of analysis? And can the incorporation of the built environment, and cultural connection, be used to identify disease clusters?Mortality locations were extracted from the ORD, and mapped in a GIS containing georegistered Sanborn and Robinson Fire Insurance maps which had been georegistered in ArcMap 9.1 . This georegistration was achieved by adding known coordinate locations to sections of the French Quarter which have remained unchanged between 1878 and now. The detail in Sanborn Insurance maps , is such that actual building addresses and other information relevant to the built environment, including number of floors, and the building's functional use can be identified. The 1878 city directory was used to verify that the address numbering scheme was the same for both the map creation year  and the year of the epidemic. As street names and address ranges were different to 2008 New Orleans, and therefore not compatible with available GIS layers, traditional address-matching approaches were impossible to perform. Other GIS based investigations of historic epidemics have created "new" street networks to allow for this approach . For thiOnce these geographic layers were created, a series of commonly used spatial analyses were performed to identify areas with high intensities of disease. At the global scale (the city of New Orleans), a spatial variant of the basic reproduction number had identified neighbourhood specific index cases and subsequent number of connected deaths to this first case . For thiA nearest neighbour hierarchical clustering (NNHC) approach was also performed in Crimestat  to identThe results of these two preliminary investigations were used to focus the geographic setting of this paper. Apart from the French Quarter having a high number of deaths, it has the additional advantage of being one of the areas of New Orleans which maintains much of the same built environment today. This could allow for future investigations to actually visit the buildings and courtyards integral to disease spread. Also, the relatively equal residential density of the city blocks found in the French Quarter, though in no way a perfect surrogate for a population denominator, do offer a geographic way of controlling for unevenness in the underlying population surface. The lower population density in Uptown with its larger homes and generally higher socio-economic level would have posed problematic if used to compare mortality surfaces with the French Quarter.A series of KD surfaces were generated for the French Quarter to investigate the spatial pattern of mortality at different spatial scales, and for different cultural subpopulations. In order to minimize boundary effects, a one block buffer including mortality locations around the French Quarter was included in the KD generation.The first of these was a KD surface for all mortalities occurring in the French Quarter for the entire epidemic with no temporal consideration. This surface can still be revealing even without a denominator population in terms of showing where the greatest loss of life occurred.ceteris paribus, children were likely to be evenly distributed across all nativities. After a few years of residence, both immigrant and US born families would have US born children, this being reflected in a lack of spatial pattern for their mortalities.This mortality surface was subdivided into four subpopulations: the three largest nativity populations , and those under the age of 5. The rationale for the inclusion of the under 5 category was that this epidemic, as previously noted, had a severe toll among children. It was expected that a KD surface of children would present no clustering as, For those assigned to the category of born in the United States, only ages greater than 10 were considered. This selection was made because children born to freshly landed immigrant families would otherwise confound patterns for "US born". Among the nativity locations included in this category were: Alabama, Baltimore, Boston, Chicago, Cincinnati, Illinois, Indiana, Iowa, Kentucky, Lafouche, Louisville, Louisiana, Maine, Maryland, Massachusetts, Michigan, Mississippi, New Jersey, New Orleans, New York, Ohio, Richmond, South Carolina, St Louis, Tennessee, Texas, and Virginia. For the French subgroup, Alsace was also included, and for the Italians, Sicily and Palermo were added as named nativity locations.The KD surfaces involved no consideration of time, in other words the density surface only captures the overall pattern of death without including temporal subtleties, or phases, of the epidemic. The previously described calculation of the spatial basic reproduction number had included an appreciation of time sequences relevant to yellow fever, mainly taking into account viremia, days to death and the extrinsic incubation period of the mosquito . HoweverAedes aegypti, though it was also suggested that the same distance could be used as a surrogate for cultural activity. This new clustering approach further focused on neighbour-to-neighbour connectivity by including that the distance had to be calculated by sight line, or along the same block face, within the three-dimensional built environment. Therefore, for two deaths to be considered as part of the same cluster, both had to be in buildings either on the same city block, visible from the building front to another building front , or from the back of the building across a shared courtyard. The temporal constraint of 21 days was selected as a conservative period linking deaths attributed to a shared index case which could result in both deaths occurring on the same day, or between 10 to 21 days if a mosquito feeds on the first infected individual, goes through extrinsic incubation, and then infects the second resulting in his/her death, a similar rationale to that employed in .Clusters of mortalities were created using the following criteria, each death was linked to a neighbouring death as long as each were within 50 meters, and both occurred within 21 days. As explained in Curtis et al (2007), 50 meters is an average flight distance of or B. As a result, clusters were expected to occupy different shapes based on the built environment, and not forming more classic circular patterns. As a result, these clusters are visualized as linked buildings, containing both those residences with mortalities, and buildings between deaths that lay on the linking path. Therefore, if mortality A and B are separated by two buildings, then these structures are also included in the cluster. A linking of deaths had to contain at least 5 mortalities to be classified as a cluster. Again, varying sizes of clusters would have produced different results, but 5 were chosen as the purpose of this exercise was to identify spatial patterns of spread at the street and building level, and larger cluster sizes may have missed many of these macro level associations.By linking mortalities in this manner, clusters were formed organically. In other words, as long as two deaths (A and B) could be linked in the manner described above, a third mortality need only be linked to A In order to more explicitly identify the impact of cultural distance, clusters identified by the above procedure were classified by dominant subpopulation as long as at least 5 members were drawn from that group. Therefore, for the smallest possible size cluster (containing 5 deaths), all mortalities would have to be of the same nativity for it to be classified as of that nativity.This cultural connection was extended further by selecting only clusters which had been associated with one subpopulation, and then removing all other mortalities from the cluster. The clustering approach was rerun on the remaining deaths using the previously defined clustering thresholds. Therefore, if a cluster had been identified as "Italian" the new cluster would still have to contain 5 mortalities  that could be linked by 50 m in the built environment, and where the mortality sequence was less than 21 days.Results from this more conservative clustering approach would then be investigated by returning to the GIS and observing the spatial pattern of mortalities and their built environment. Although the numbers involved at this scale would be too small to produce results by any global investigation, it was hoped that visual inspection of the house-to-house disease pattern would reveal further spatial connectivity.As with all historic epidemiology, one must be careful of misdiagnosis at the time as there was no serological testing. Other sources of error include data entry, cultural reporting biases and epidemic-caused underreporting -29 The sThe first investigation of the French Quarter involved creating a KD surface to show the overall pattern of disease intensity. This can be seen in Figure Figure Although these KD surfaces show the general spatial pattern of mortalities, they do not capture either temporal complexities or spatial subtlety. In order to investigate this space and time complexity, a cluster approach was developed to incorporate the temporal relationship relevant to yellow fever and the built environment. Using this method, twenty-two clusters (with at least 5 members) were identified, which when mapped by their dominant subgroup revealed a spatio-temporal-cultural sequence. Table What is interesting from this cluster patterning is that there appears to be disease progression that follows cultural (nativity) connections more so than distance. French cluster 1 and 2 are not geographically proximate, but they do follow sequentially. Similarly, if one were to expect a contagious diffusion, then the Italian Clusters should follow soon after French Cluster 2, but in fact there is a 22 day difference before the first case in Italian Cluster 7. One difference between the French and Italian clusters is that there is a temporal separation between Clusters 1, 2 and 3, and then 4 and 5, while Italian Clusters 6, 7 and 8 are all within 6 days and closely packed together. If we again refer back to the NNHC Figure A further cultural refinement of the clusters methodology only accepts members from the same subpopulation, for example all French or Italian. This results in the original 22 clusters being reduced to six. In addition, one of these original clusters is split into two  because the distance between the closest elements in either of the sub-clusters is greater than 50 m. Each of these sub clusters still has at least five members. All of the Italian clusters remain, while only two of the six French clusters meet requirements.rd to September 11th, the second ranging from August 24th to September 8th, and the last ranging from September 1st to October 8th. This last clustering apparently occurs later in the epidemic sequence than the other two which are more contemporary to each other.In order to investigate the final (largest) scale of disease patterning, these six clusters were visualized at the street level. Figure Spatial patterns associated with the yellow fever epidemic of 1878 have been previously discussed in the literature even if not from a spatial analytical perspective. These include the spread from initial point of entry within New Orleans, the spread throughout Louisiana and then along the Mississippi, the spread through neighbourhoods of New Orleans, and concurrently neighbourhoods of Vicksburg, Mississippi, and Memphis Tennessee. Therefore, even though the spatial pattern of an epidemic can be identified and visualized at multiple scales, this final pattern is actually the result of mini-epidemics. Similarly Bailey  suggestsThis paper has shown that the French Quarter emerges as a hotspot in two different citywide analyses. One of these analyses also incorporates the element of time (by month) suggesting that disease was prevalent in this area for a considerable period of the epidemic. A second analysis just considering mortalities within the French Quarter identifies this hotspot to be connected to Italian immigrants. A third analysis designed to create neighbourhood clusters, shed further light on this hotspot by revealing that two nativities were actually involved in the creation of the hotspot; French natives in August, and Italian natives in September. A fourth more stringent cultural clustering approach reveals that one of the mini-epidemics comprising the hotspot can be further subdivided into two sub-clusters, which if visualized on a final building-level map reveals three street-level groups. Therefore, for this one identified hotspot revealed through a city-level analysis, we finally emerge with three neighbouring groups comprised of Italian families.The clustering approach presented in this paper also reveals further cultural patterns. For the early part of disease progression into the French Quarter, it appears that disease spread through French nativity enclaves. The connection between cases does not follow a typical contagious diffusion processes because two of the first clusters were spatially separated. Instead the spread was connected to nativity. Indeed, the importance of geographic distance only appears to be relevant if neighbourhoods of similar nativity were proximate. Obviously this finding is exploratory and requires more extensive testing, using either other neighbourhoods from the same city and epidemic, or other cities and epidemics as long as data are available in a similar format.The ability to investigate these scale-dependent patterns to the epidemic, and to consider how the built environment and nativity affect spread, are only made possible by the analysis of historic data within a GIS. This paper has shown that the spatio-cultural living environment of Italian families apparently resulted in an increased disease susceptibility. This finding has not previously received similar attention in commentaries about this epidemic where writers are reliant on contemporary accounts and no subsequent data analysis. What is even more interesting is that in another paper utilizing GIS, Tuckel et al. (2006), describe how southern or eastern European immigrants were more susceptible to the 1918 influenza virus. In their paper they also cite a 1920 study by Winslow and Rogers who specifically identify Italians as being twice as susceptible (in proportion) to the overall epidemic . It woulThe results of this paper could also provide several research avenues for historians to follow. For example, what was the average length of time since immigration in the cluster neighbourhoods? What were the mobility patterns (daily commutes) and social networks for immigrants living in these cluster areas? To what degree was there neighbourhood segregation based on nativity?at what geographic distance does this cultural distance finally break down? In some way this mirrors suggestions by Massad [0 of > 1, which is a basic reproduction number one would expect in neighbourhoods of a high ethnic intensity and therefore social interaction [The relevance of this paper to current epidemiology is in the suggestion of how to protect against a newly emerging infection, or even a bioterrror release. The traditional approach would be a combination of vaccination and cordon sanitaire. The primary rationale for this is space based – a buffer of exclusion being calculated from a distance decay of disease risk. However, this paper suggests  that diffusion occurs based on both cultural distance and geographic distance. Therefore if an outbreak occurs in one ethnic community of Los Angeles, for example, is it more prudent to identify similar cultural areas across the city in which to target intervention as well as simply ring vaccinate? One question for future research would be, y Massad  that maseraction .The author declares that they have no competing interests.AC performed all analyses and writing of this paper


There has been a renewed debate over whether AIDS deserves an exceptional response. We argue that as AIDS is having differentiated impacts depending on the scale of the epidemic, and population groups impacted, and so responses must be tailored accordingly. AIDS is exceptional, but not everywhere. Exceptionalism developed as a Western reaction to a once poorly understood epidemic, but remains relevant in the current multi-dimensional global response. The attack on AIDS exceptionalism has arisen because of the amount of funding targeted to the disease and the belief that AIDS activists prioritize it above other health issues. The strongest detractors of exceptionalism claim that the AIDS response has undermined health systems in developing countries.We agree that in countries with low prevalence, AIDS should be normalised and treated as a public health issue--but responses must forcefully address human rights and tackle the stigma and discrimination faced by marginalized groups. Similarly, AIDS should be normalized in countries with mid-level prevalence, except when life-long treatment is dependent on outside resources--as is the case with most African countries--because treatment dependency creates unique sustainability challenges. AIDS always requires an exceptional response in countries with high prevalence (over 10 percent). In these settings there is substantial morbidity, filling hospitals and increasing care burdens; and increased mortality, which most visibly reduces life expectancy. The idea that exceptionalism is somehow wrong is an oversimplification. The AIDS response can not be mounted in isolation; it is part of the development agenda. It must be based on human rights principles, and it must aim to improve health and well-being of societies as a whole. Countries are struggling to deliver on their pledges for universal access to a comprehensive set of interventions for HIV prevention, treatment, care and support, while the global economy is in crisis. At the same time there has been a renewed debate over whether AIDS deserves an exceptional response. This dispute has divided scientists, civil society, researchers and policy-makers. While deliberation is important, we must maintain focus on the 7000 people who are newly infected with HIV every day, and on those who continue to die from a treatable and preventable disease.The many AIDS epidemics affect countries and specific groups in various ways and to differing degrees. In Swaziland, 26 percent of the adult population is infected, in Kenya 7.1 percent is infected, while in Canada, only 0.4 percent is infected. South Africa, has the highest number of people living with HIV and AIDS in the world - an estimated at 5.7 million men, women and children [In wealthy countries, localized epidemics occur in specific contexts. On Vancouver's Downtown Eastside, the infection rate amongst commercial sex workers is 26 percent . In the In the early 1980s, AIDS was a new disease from an unknown retrovirus; its mode of transmission was mysterious, initially affecting mostly the gay population in the West. Its exceptional status was promoted through an alignment of interests of the medical community and gay advocates . There wThe Global Infectious Disease Threat and Its Implications for the United States' [th International AIDS Conference, in Durban in 2000, the inequity of treatment was highlighted. AIDS had become a chronic disease in the West, and a death sentence elsewhere. Activists demanded that the drugs, which were beyond the reach of most people in the developing world, should be made universally available.Internationally, AIDS became increasingly 'globalised.' In 2000, the United States National Intelligence Council (NIC) produced the ' States' . Six mon States' . At the Manufacture and sale of generic drugs, plummeting prices and growing international initiatives, resulted in an astonishing treatment roll-out, making the response once again exceptional. The costs of ART fell from about $10,000 per patient per year to $350 in the early 2000s . In 2002In our view, AIDS exceptionalism is under attack from two sources. The first were characterized by Stephen Lewis, speaking at the International AIDS Society Conference on Pathogenesis, Treatment and Prevention in Cape Town in July 2009, as: "the pinched bureaucrats and publicity-seeking academics who advocate exchanging the health of some for the health of others - who propose robbing Peter to pay Paul rather than arguing, in principled fashion, that money must be found for every imperative, including maternal and child health, and sexual and reproductive health, and environmental health as well as all the resources required to turn the tide of the AIDS pandemic" . The secA series of books and articles set out the exceptionalism debate. Chin argued UNAIDS and AIDS activists perpetuate certain myths about the epidemiology of HIV so as to keep the disease on the political agenda and, by implication, ensure funding and jobs . Pisani The strongest  arguments were advanced by England, who claimed that AIDS financing has undermined health systems in developing countries ,18. He aThe realization that AIDS programs have sometimes, in their single-minded zeal for results in less than optimum contexts, been misinformed and poorly planned should be taken as constructive criticism, instead of eliciting defensive responses. We know funding has not always been applied where it is most required. For example, in West Africa sex trade workers are a core transmitter group, but most prevention funding is applied to the general population. The Commission on AIDS in Asia found that almost 90 percent of all investment in prevention went to areas with insufficient returns . PlanninThere is also the issue of what Peter Piot, former UNAIDS Executive Director, describes as "The health system's myth. The myth that if we just, if we only strengthen health systems this will solve everything, including AIDS" . The impIn October 2008, the Lancet wrote "A view beyond HIV/AIDS will reinforce plurality and justice, protecting minorities and thus wider majorities" . In counAddressing AIDS as a 'normal' public health issue counters the stigma that is directed towards at risk groups by labeling them as 'different;' instead of getting 'special treatment' they get the treatment they deserve. This could offset the tendency of some governments to shirk responsibility for providing for these groups by labeling them as 'special interest groups' or those who make specific 'life style choices.'A 'normal' public health response is also necessarily adaptable; most at risk population groups are not static. For example, in Russia, young male injection drug users were recognized as the most at risk group until recently. However, the proportion of infections amongst women rose from 13.0 percent in 1995 to 44.0 percent in 2006 , indicatSimilarly, AIDS should be normalized in countries with mid-level prevalence, except when life-long treatment is dependent on outside resources - as is the case with most African countries - because treatment dependency creates unique sustainability challenges. Once treatment begins, medications must be taken for life. The drugs are expensive and patients will, after a period of time, need to move from first-line (costing about $92 per patient per year) to second-line treatment (at about $1214 per patient per year) . The reqBetween 2005 and 2008, 60 percent of funding for AIDS responses in sub-Sahara Africa came from multilateral, bilateral and philanthropic organizations, and more than half of AIDS funding came from the United States . In MozaPlanning for HIV and AIDS funding also demands urgency: the current economic crisis, which has hit the United States particularly hard, threatens the sustainability of AIDS funding. It is unlikely the required US $25.1 billion for low- and middle-income countries for treatment and prevention programs in 2010 will be forthcoming . The chaEven where treatment is available, AIDS requires an exceptional response in countries with high prevalence (over 10 percent) due to the need to provide treatment or face increased morbidity and mortality, and the continued challenges of implementing effective prevention programs. High incidence of AIDS related illness and death has demographic and social impacts that will be felt for generations. Life expectancy declines, the size and the structure of the populations changes, and numbers of orphans increase. For example, in Botswana life expectancy fell from 56 years during the period 1970 to 1975; to 46.6 years in 2000 to 2005 . In SoutIn high prevalence countries the epidemic has a particularly unique and troubling characteristic, often referred to as 'the feminisation of AIDS' . In SoutIn the context of high levels illness and mortality, the HIV and AIDS response also must recognize the increased care burden placed on women. UNAIDS estimates that 90 percent of HIV and AIDS related caregiving in sub-Sahara Africa is done in the home , and theIn high prevalence contexts AIDS must be mainstreamed across a nation. For example, in education there will be issues of teacher deaths, children living with HIV and the need to prevention programmes; in agriculture HIV/AIDS may be implicated in lower production . The heaWe have argued that AIDS is exceptional but that that response should not be mounted in isolation. The Maximizing Positive Synergies report identifies a range of opportunities for building on the results-based programmes established to address HIV and AIDS to strengthen health sectors and systems . For exaThe idea that exceptionalism is somehow wrong is an oversimplification. While normalizing the response where AIDS is located largely in specific population groups can ensure equitable services and treatment by addressing stigma and discrimination. AIDS must be seen as exceptional in those places where it is having long term development impacts due to high incidences of illness and death. Critics of AIDS exceptionalism do not take into account the unique situation where international aid is literally keeping people alive. In high prevalence countries, prevention programs have yet to slow the rate of infection, and finding ways to do so will require creativity and an unprecedented political commitment. The AIDS response can not be mounted in isolation; it is part of the development agenda. It must be based on human rights principles, and it must aim to improve health and well-being of societies as a whole.The authors declare that they have no competing interests.These authors contributed equally to this work.


We aimed to develop a new scale for evaluating risks and preventive measures for in-hospital falls of newborn infants, from admission to discharge of the expectant mother. Our study was prepared in accordance with Failure Modes and Effects Analysis criteria. The risks and preventive measures for in-hospital falls of newborns were determined. Risk Priority Numbers (RPNs) were determined by multiplication of the scores of severity, probability of occurrence, and probability of detection. Analyses showed that risks having the highest RPNs were the mother with epidural anesthesia (RPN: 350 point), holding of the baby at the moment of delivery (RPN: 240), and transportation of baby right after delivery (RPN: 240). A reduction was detected in all RPNs after the application of preventive measures. Our risk model can function as a guide for obstetric clinics that need to form strategies to prevent newborn falls. Operative and vaginal deliveries are among the most commonly performed procedures in hospitals. However, they have a lot of risks, and one may encounter some unpredictable and undesired complications at delivery. The risks for a newborn, including the risks for falling, start with the onset of labor. Falling incidents are particularly encountered at overcrowded delivery and education hospitals, and trauma incidents resulting from falling occur but unfortunately not put on the record. There are a limited number of publications in the literature regarding traumas resulting from in-hospital falls of newborns but there is no scale evaluating the risks and risk reduction measures –3. In a As a part of health care quality and insurance preoccupations some scoring systems have been developed for adult patients –7. The fOur hospital has been accredited by the Joint Commission International (JCI) in 2006 and our intention is to improve the standards and care quality of the newborn and the mother. The Department of Gynecology and Obstetrics also provides neonatology service in Bayındır Hospitals since the foundation of the hospital. In line with the quality improvement services, we intend to prevent or minimize the risks of newborn falls, although we have not encountered any in-hospital falls in newborns till today. Failure Modes and Effects Analysis (FMEA) is a proactive technique that is most often used to identify and address problems before they occur , 13.In an attempt to identify the risks beforehand, we aimed to develop a new scale for evaluating the risks and preventive measures for in-hospital falls of newborn infants, from admission to the discharge of the expectant mother and the baby, by using FMEA.Our study was prepared in accordance with the FMEA criteria. A quality improvement team including an obstetrician, a neonatologist, nurses, and quality staff, who were involved in the process, was formed in order to determine the risks and preventive measures for in-hospital falls of newborns. The team worked for 20 hours at 10 sessions, each of which lasted 2 hours, between January and March 2009. Risks, which might be encountered throughout the process, were defined in accordance with FMEA. Firstly, the phases of delivery process, from hospitalization until discharge, were defined as follows: the process before the delivery took place, the delivery process, the transfer of the neonate, and the process of care. The preventive measures, their applicability and efficacy were reviewed. For the probable risks, scores of severity, probability, and predictability were calculated in accordance with the criteria of FMEA. Risk Priority Number (RPN) for each risk was determined by the multiplication of the calculated scores of severity of effect (S), probability of failure (PF), and probability of detection of an existing defect (P). (S × PF × P = RPN). “Bayındır Hospital Risk Evaluation Scale for In-hospital Falls of Newborn Infants” was developed . RPNs weThe risks determined for in-hospital falls of newborn infants are presented in Analyses showed that risks that have the highest RPNs are the mother with patient controlled analgesia (PCA) (RPN: 350 point), holding of the baby at the moment of delivery (RPN: 240), and transportation of the baby right after the delivery (RPN: 240). The other risky conditions were sorted as the patient standing up when the cervix was dilated greater than 5-6 cm (RPN: 180) and the ones that might occur during the basic care of the baby (RPN: 180). After the preventive measures against these risks were implemented rescoring was performed. RPNs of all risks were reduced; the RPN of the mother with PCA dropped to 60, of the baby falling at the moment of delivery and transportation to 40 .The interest in risk assessment tools and preventive measures for in-hospital falls has been gradually increasing in the recent years by the broad implementation of quality management tools and techniques in the hospitals. Up to date, a number of scales predicting the risks of hospital falls, especially for elderly patients have been developed , 7. HoweTrauma cases resulting from falling are rare in newborns, but they may be fatal . As mostSince the accreditation of our hospital, we have been working on quality management in all departments of our hospital. Within the scope of quality of service improvements, we wanted to take precautions against hospital falls, though no cases of newborn falls have been reported in our hospital till now. As no scoring system was developed for newborn falls, we used the FMEA method used mainly in other sectors , 15 and We use the “Bayındır Hospital Risk Evaluation Scale for In-hospital Falls of Newborn Infants” in routine monitoring of the babies, along with the monitoring of the vital signs at 3-hour intervals. Besides the precautions taken, nursing support is provided to the babies with high risk scores. A problem encountered in our study was the over-estimation of risky cases, because the high risk threshold was set at a lower level in the scale. We will overcome this handicap by the evaluations performed at each 6 months as indicated in the algorithm, and we will implement new statistical support for our assessments.Traumas resulting from falling inside the hospital are preventable. Newborn falls may be a serious problem particularly in obstetric clinics of overcrowded hospitals. In an effort to prevent newborn falls before happening, in this prospective study we developed, a scale in accordance with the FMEA. FMEA is a systematic method of resolving and detecting the problems before it starts and aims to properly evaluate a process or product for strengths, weaknesses, potential problem areas, or failure modes, and to prevent problems before they occur. Our results suggest that the most risky situations for newborn falls are the mother with epidural analgesia, holding of the baby at the moment of delivery, and transportation of the baby right after the delivery. After the development of the scale, we implemented all the preventive measures to overcome these risks in our hospital.Each hospital where delivery operations are carried out, especially those with large patient numbers, must apply necessary precautions suitable for their hospitals to minimize the risks. We believe the scale we developed and the systematic application used in our study will contribute to the literature as to minimizing the risk of trauma of a newborn resulting from falling. We think our study can function as a source for obstetric clinics that need to form strategies and clinic manuals to prevent trauma of a newborn resulting from falling. A work strategy for the prevention of in-hospital falls of the newborns should be determined and applied at each hospital.


The autism spectrum disorders are a group of conditions with neurobehavioral impairment affecting approximately 0.6% of children. The clinical presentation is complex and the etiology is largely unknown, although a major role of genetic factors is widely accepted. A number of genetic studies led to the identification of genes and/or copy number variants whose alterations are associated with autism, but no specific factor has been found so far to be responsible for a substantial proportion of cases. Epigenetic modifications may also play a role, as demonstrated by the occurrence of autism in genetic conditions caused by mutations in imprinted genes or regions.et al. published this month in BMC Medicine, reports on genomic and epigenetic alterations of OXTR, the gene encoding the receptor for oxytocin. The involvement of this gene was suggested by its deletion in an autistic patient. The subsequent analysis of a group of unrelated autistic subjects did not show an OXTR deletion, but rather hypermethylation of the gene promoter, with a reduced mRNA expression.The article by Gregory These findings address two major points of the current debate on the etiology and pathogenesis of autism: the role of oxytocin, known to be involved in modeling human behavior, and the possible involvement of epigenetic mechanisms. The nature of this epigenetic dysregulation is unknown but, if proved to be true, might explain the failure to identify sequence alterations in a host of candidate genes. Practical implications of these findings may be forthcoming, however not before extension and validation on a larger scale have confirmed their value.See the associated research paper by Gregory et al:  BMC Medicine, Gregory et al. [This month in y et al.  report oThe autism spectrum disorders (ASDs) are a group of neurodevelopmental conditions characterized by impairment in social, emotional and communicative skills and by stereotyped motor and mental processes with an onset in the first 3 years of life. ASD affects approximately 0.6% of children. The numRegarding the etiology, it is generally accepted that genetic factors play a major role and it has become clear that, with the exception of a minority of instances (about 1%) in which the phenotype is caused by a single gene alteration, the genetic component leading to autism is complex, being based on interactions of multiple genetic changes and/or epigenetic regulation of gene expression.de novo CNVs, some non-randomly associated with ASD, although none of these have been so far proven to harbor major genes causing or predisposing to ASD.Because of this complexity, decades of experimental work, even with the aid of sophisticated molecular genetic tools  array platforms) have failed to identify specific causes in any substantial proportion of cases ,5. NonetLikewise, several biological parameters, such as the postsynaptic receptor density ,8, the iBMC Medicine, Gregory et al. show that there is genomic and epigenetic evidence of a reduced function of the oxytocin receptor in autism. They identified a genomic deletion containing the gene encoding for the oxytocin receptor (OXTR) in an autistic male individual and in his mother, who probably experienced obsessive-compulsive disorder (OCD). The equally affected brother did not have the same deletion but rather a hypermethylation of specific CpG islands likely to cause a reduced expression of the OXTR gene. It would be interesting to know the methylation status of the OXTR allele also in the deleted proband and in the mother, and to measure its level of expression. Likewise, one would want to know whether the maternal deletion was de novo or inherited. Could the OXTR gene be imprinted? So far there is no evidence of a possible monoallelic, parental-specific expression in any tissue.This month in OXTR gene in a number of samples from autistic subjects, including brain tissue from the temporal cortex as well as peripheral blood lymphocytes. Although the sample is not a large one, the authors found a hypermethylation of specific CpG islands and a correspondingly reduced expression of the OXTR gene. This brings up the question of how did this hypermethylation occur? Was it environmentally induced or genetically determined?Regardless, the above findings prompted the analysis of the methylation status of the et al. address two major points in the current debate on the cause and pathogenesis of autism: one related to the role of oxytocin and its receptor, the other to the possible role of epigenetic mechanisms.The findings of Gregory OXTR genes [OXTR gene, have been associated with a pervasive developmental disorder in a patient with obesity and behavioral issues [OXTR expression can cause behavioral phenotype falling within the ASD spectrum.Regarding the former, there is growing evidence that the oxytocin-vasopressin pathway has an influence on social behavior both under normal circumstances and in a clinical setting ,20,27,28TR genes ,30-32. Dl issues , thus suet al. deals with the epigenetic inhibition of OXTR expression in ASD. Such epigenetic modification, at least as reported so far, does not seem to be sequence based but rather of a different, as yet unknown nature. This might explain why researchers have been looking for decades for genetic mutations in ASD and yet have found almost none. An epigenetic mechanism would justify the 'unusual', non-Mendelian familial aggregations of ASD. In this respect, even the family with OXTR deficiency reported by Gregory et al. shows an unusual genotype-phenotype correlation, in that the same phenotype is caused by alterations of the same gene but due to different molecular defects (deletion versus hypermethylation).The second issue raised by Gregory Also, the possibility that in most ASD patients there might be an epigenomic instability is of interest in consideration of the fact that it has been shown that the epigenetic status in early fetal development can be reprogrammed by maternal behavior in a reversible way . TherefoThe epigenetic nature of ASD has been already suspected based on many instances, such as the association of ASD with conditions caused by mutations of imprinted genes like Angelman, Fragile X or Rett syndromes, or with quantitative alterations in regions like the 15q11-q13, also known to be imprinted .et al. seem to open new avenues in the research on ASD, one involving the oxytocin pathway, the other the human methylome. Thus, future research in the field may take sharp turns, searching for genetic alterations responsible for ASD beyond DNA sequencing and into epigenetic regulation of gene function. Of course, before these findings can be applied as diagnostic tools or biomarkers of ASD, or can even lay down a basis for therapeutic approaches, it is necessary to confirm them in larger cohorts of patients and controls. It is true that in ASD replication studies have often failed, although this should not stop us from striving to solve this puzzle. Time and further studies will tell us whether the results seen here live up to their initial promise.The findings by Gregory The authors declare that they have no competing interests.Both authors contributed equally to the writing of this article.The pre-publication history for this paper can be accessed here:


We examined which adaptive coping strategies, referring to the concept of 'locus of disease control', were of relevance for patients with chronic pain conditions, and how they were interconnected with patients' life satisfaction and interpretation of disease.In a multicenter cross-sectional anonymous survey with the AKU questionnaire, we enrolled 579 patients (mean age 54 ± 14 years) with various chronic pain conditions.Trust in Medical Help; Search for Information and Alternative Help), but also on internal powers and virtues . In contrast, Trust in Divine Help as an external transcendent source and Reappraisal: Illness as Chance as an internal (cognitive) strategy were valued moderately. Regression analyses indicated that Positive Attitudes and higher age were significant predictors of patients' life satisfaction, but none of the other adaptive coping strategies. While the adaptive coping strategies were not associated with negative interpretations of disease, the cognitive reappraisal attitude was of significant relevance for positive interpretations such as value and challenge.Disease as an adverse interruption of life was the prevalent interpretation of chronic pain conditions. As a consequence, patients relied on external powerful sources to control their disease  and positive interpretations of disease. To restore a sense of self-control over pain (and thus congruence with the situation), and the conviction that one is not necessarily disabled by disease, is a major task in patient care. In the context of health services research, apart from effective pain management, a comprehensive approach is needed which enhances the psycho-spiritual well-being of patients.The experience of illness may enhance intensity and depth of life, and thus one may explain the association between internal adaptive coping strategies (particularly  There are different ways to cope with pain, and there are different ways to regulate emotions associated with chronic diseases. Because most patients with chronic diseases are unable to 'solve' their persisting pain conditions by themselves (in terms of recovery or repair) and to find distance to negative emotions associated with pain, they have to find strategies to adapt to a long-lasting course of disease. Patients have to find ways to maintain physical, emotional and spiritual health despite of often long-lasting courses. Thus, patients' coping with chronic pain is an ongoing process which includes appraisals of stress, cognitive, behavioural, and emotional coping responses, and subsequent reappraisals of stress.One of the most frequently used concept on adaptation strategies of patients with chronic pain diseases differentiates active and passive coping ,2. ActivA recent meta-analysis found that among older adults with persistent pain, the most frequently reported coping strategies were Task Persistence , Pacing (activity avoidance), and Coping Self-Statements ; the least frequently used strategies were Asking for Assistance and Relaxation . FindingTrust in Medical Help; Search for Information and Alternative Help; Trust in Divine Help) and internal sources  [Our own study results suggest that most patients with chronic diseases use adaptive coping strategies which can be differentiated according to the utilization of external resources of health control  ,5. Parti Chance) . These iIn this report, we intended to analyze which adaptive coping strategies referring to the concept of 'locus of health control' , were of relevance for patients with chronic pain conditions, and how these strategies were associated with patients' life satisfaction and interpretation of illness. Our hypothesis was that particularly the adaptive coping strategies referring on the internal resources are associated with life satisfaction, while positive interpretations of illness  are related to reappraisal processes.For this multicenter cross-sectional survey, patients were recruited from the acute pain outpatient clinic of the Communal Hospital in Herdecke, from the Department of Internal and Integrative Medicine at the Essen-Mitte Clinics, from the Orthopaedic Clinic in Bad Bocklet and from the orthopaedic Baumrain Clinic in Bad Berleburg. Their institutional heads gave approval to run this anonymous survey. All enrolled individuals were informed of the purpose of the study, were assured of confidentiality, and consented to participate. The questionnaires were anonymous , and the pooled data could not be tracked back to individual patients.To minimize the bias of a 'convenience sample', different medical centres in West-Germany were chosen, and patients were recruited consecutively as they attended the respective clinics. To obtain a more naturalistic sample, we had neither inclusion nor exclusion criteria (with the exception of the diagnosis chronic pain disease and consent to participate). We did not measure pain intensity scores, and thus we categorized the patients according to the recruiting source which indicated differences with respect to the need for acute interventions .The demographic data of 579 (out of 607) patients which provided enough data for statistical analyses were depicted in table Adaptive coping strategies in response to chronic pain conditions were measured with the AKU questionnaire (AKU is an acronym of the German translation of "Adaptive Coping with Disease"), which was designed to identify adaptive coping styles, such as to create favourable conditions, search for information, medical support, religious support, social support, initiative spirit, and positive (re)interpretation of disease ,5,7. TheTrust in Divine Help in response to disease addresses non-organized intrinsic religiosity as an external transcendent resource to cope .▪ Trust in Medial Help addresses patients' reliance on an external medical source of health control .▪ Search for Information and Alternative Help refers to external sources providing additional information or alternative help .▪ Conscious Way of Living addresses cognitive and behavioural strategies in terms of internal powers and virtues .▪ Positive Attitudes refers to internal cognitive and behavioural strategies .▪ Reappraisal: Illness as Chance addresses a reappraisal attitude referring to cognitive processes of life reflection .▪ The items of the AKU were scored on a 5-point scale from disagreement to agreement . The sum scores were referred to a 100% level . Scores > 50% indicate high agreement or utilization of coping strategy, while scores < 50% indicate low usage of respective strategy.Escape from illness  coping style [Escape correlated strongly with depression, with disease appraisals such as 'weakness/failure' and 'punishment', and negatively with life satisfaction [The questionnaire holds 3 independent items, which did not contribute to the primary AKU item pool. They made up an independent scale termed ng style ,5,7, whisfaction . The iteTo measure how the patients interpret their disease, we used the 'Interpretation of Illness Questionnaire' (IIQ)  which reLife satisfaction was measured with the Brief Multidimensional Life Satisfaction Scale (BMLSS) . The eigAnalyses of variance (ANOVA), correlation and stepwise regression analyses were performed with SPSS for Windows 17.0. We judged p < 0.01 as significant. With respect to the correlation analyses, r > .5 is regarded as a strong correlation, r between .3 and .5 as a moderate correlation, while r between .2 and .3 is regarded as a weak correlation, and r < .2 as no or negligible correlation.Escape from illness, as a passive avoidance-escape strategy, was not a major issue to the patients  with chronic pain conditions (mean duration of disease: 96 ± 116 months). As shown in Table Trust in Medical Help; Search for Information and Alternative Help) and on internal powers and virtues , while the transcendent external locus of disease control , and also Reappraisal: Illness as Chance were valued moderately . Age had a significant (p < .0001) impact on Trust in Divine Help (F = 10.4), Trust in Medical Help (F = 5.2) and Conscious Way of Living (F = 4.8). Duration of disease had no significant impact on the adaptive coping strategies ; however, Conscious Way of Living showed in trend some degree of variance .The patients with chronic pain conditions analyzed herein relied on both external powerful sources to control their disease  of life Figure , particuTo analyse how the adaptive coping strategies, life satisfaction and interpretation of disease were associated, we first performed correlation analyses Table .Conscious and Healthy Way of Living correlated strongly with Positive Attitudes, and moderately with Search for Information/Alternative Help and Trust in Devine Help, while Positive Attitudes were just weakly associated with external adaptive coping strategies or Reappraisal. In fact, Reappraisal: Illness as Chance correlated best with Trust in Divine Help, weakly with the other strategies, but not with Trust in Medical Help.Among the intrinsic styles, Trust in Medical Help, this strategy was moderately associated with Search for Information/Alternative Help which is plausible from a theoretical point of view, and consistently not with depressive Escape from Illness.With respect to Escape from Illness (which is not regarded as an adaptive coping strategy) was associated weakly negative with life satisfaction and Positive Attitudes, but with none of the other adaptive strategies.Trust in Medical Help. Among the interpretations with a negative connotation, none correlated with the adaptive coping strategies - there was just a weak positive association between Trust in Medical Help and adverse Interruption/Loss and a weak positive correlation between Reappraisal and Weakness/Failure  correlated weakly with adaptive coping strategies, but not with re Table . Yet, alConscious and Healthy Way of Living and Positive Attitudes, while Trust in Medical Help and also the Reappraisal attitude did not correlate. Moreover, life satisfaction did not significantly correlate with the positive disease interpretation Value (r = -.055) or Challenge (r = .061).Life Satisfaction was moderately associated particularly with active internal strategies Escape from Illness (data not shown), and just marginally with life satisfaction .Duration of disease did neither significantly correlate with the adaptive coping strategies nor with To determine the relevance of the obvious intercorrelations between adaptive coping strategies on the one hand, and life satisfaction and positive interpretations of disease on the other hand, we performed regression analyses. The variables were enrolled on the basis of variance and correlation analyses. For this analysis, the positive interpretations of disease  were combined to a single factor.Positive Attitudes and age were positive predictors of life satisfaction, while Conscious and Healthy Way of Living (which was strongly correlated with Positive Attitudes) had just a marginal influence. Particularly Reappraisal, which was not among the relevant predictors of life satisfaction, exhibited some degree of collinearity. With respect to the positive interpretation of disease, Reappraisal: Illness as Chance had a significant influence, but none other adaptive coping strategies  which is a rather passive strategy. The reliance on medical specialists to control or manage the problem of chronic pain nevertheless may go along with  cognitive-behavioural changes, i.e., patients may change distinct aspects of their life, try to become more consciously, healthy, physically fit, use distinct diets etc. , or try to think positive, resolve cumbering situations of past, realize shelved dreams and wishes etc. ; both are active strategies. However, in face of an insufficient manageability of chronic pain, some patients may call upon 'more powerful' external others , because the conventional resources of help seem to be (subjectively) exhausted. Although the adaptive coping strategies may change during the individual course of disease, the mean scores did not significantly differ with respect to the duration of disease in the whole group. There were no steady-going courses of the adaptive coping strategies but transient trends with strong variances, indicating that the individual reasons to utilize a distinct strategy cannot be explained by duration of disease alone but by several influences .This study describes the use of adaptive coping styles referring to the concept of 'locus of disease control' among patients with chronic pain conditions. Most patients tended to externalize the process of disease management, i.e., the chronic pain disease was regarded as an adverse interruption of life, and thus patients called experts for help , and followed their advices or relied on the effects of prescribed remedies  and not Conscious Way of Living ; all other adaptive coping strategies and also the positive interpretations of disease  did not significantly contribute to life satisfaction. This means that the cognitive behavioural strategy which relies on the intention of positive thinking, the avoidance of constantly thinking at illness, and the intention to take life in own hands, the realization of shelved dreams and wishes, the resolving of cumbering situations of the past and doing all that what pleases is of outstanding importance for patients with chronic diseases to cope. One might interpret this behaviour as patients' intention to leave the role model of a 'passive sufferer', and to become an active, self-actualizing individual.In terms of life satisfaction, particularly the internal coping strategy Nevertheless, it is important to point out that even patients with impaired perception of health status can have high satisfaction with various dimensions of life concerns, i.e., they may have ground or find satisfaction in the relations with friends and families etc. While it is true that patients with chronic disease may experience decreased quality of life and life satisfaction, it is not necessarily true for all individuals. In a recent study we have shown that several dimensions of life satisfaction of patients with chronic pain diseases can score high despite of the experience of chronic pain .Reappraisal) and positive interpretations of disease. This means, patients have to find access to adequate resources - whatever these may be. Active adaptive coping strategies were not among the significant predictors of positive interpretations, but Reappraisal .According to Lipowski's original thesis, the experience of illness may enhance intensity and depth of life , and thuEscape from Illness. Nevertheless, those who relied on a transcendent resource to cope  may regard their disease as a challenge or value. This unique view that illness could be a challenge or something of value can be found particularly in cancer patients [In contrast to cancer patients who regard their disease either as an interruption of life or even as a challenge, the patients with chronic pain conditions investigated herein predominantly regarded their disease as a loss. Consequently, patients' negative interpretations of disease were associated with patients ,18,19.Escape from Illness and the highest trust in external help  as compared to patients from the rehabilitation clinic or patients attending the mind-body program. Because we had no access to reliable data on patients' intensity of pain (which limits the interpretation of data), we can just assume that patients from the acute pain out-patient clinic had higher pain intensities as compared to the patients from the rehabilitation clinic and the mind-body training programs. In fact, they seemed to have had the strongest need for external intervention. Nevertheless, despite of their obvious needs, they retained the attitude to care for themselves  and to retain Positive Attitudes in life. Why the patients from the mind-body training program had lower score for the adaptive coping strategies remains to be clarified in longitudinal studies, because one may assume that - even if their attitudes are significantly different at the start of the program - the utilization of these strategies may change during the intervention program.A limitation of the paper is that we relied on data from a cross sectional study. The adaptive coping strategies may change during the course of disease, and patients have to adapt their strategies to changing situations. This has to be address in future longitudinal studies. It was striking that particularly patients from the acute pain outpatient clinic, which attended the clinic because of severe and acute pain episodes, had both the highest scores for Nevertheless, to restore a sense of self-control over pain as well as the conviction that one is not necessarily disabled by disease and that pain is not necessarily a sign of damage  is a majReappraisal) and positive interpretations of disease. In the context of health services research, apart from effective pain management, a comprehensive approach is needed which enhances the psycho-spiritual well-being of patients with chronic pain diseases.The experience of illness may enhance intensity and depth of life, and thus one may explain the association between internal adaptive coping strategies (particularly The authors have no competing interests, and were free to interpret the data according to a strict scientific rationale. We disclose any funding received for this work from any organization.AB initiated the project, analysed and interpreted the data, and has written the manuscript. TO contributed to data analysis and the writing of the paper. EAMN and PH contributed to interpretation and the writing of the paper. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/507/prepub