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1.  Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets 
PLoS ONE  2009;4(9):e7162.
The NIAID (National Institute for Allergy and Infectious Diseases) Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org) has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2) The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3) Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and prioritization of ten potential diagnostic targets from Bacillus anthracis. The integrative analysis across data sets from multiple centers can reveal potential functional significance and hidden relationships between pathogen and host proteins, thereby providing a systems approach to basic understanding of pathogenicity and target identification.
doi:10.1371/journal.pone.0007162
PMCID: PMC2745575  PMID: 19779614
2.  Consumption After a Diet Violation Disinhibition or Compensation? 
Psychological science  2009;20(10):1275-1281.
Previous research, restricted to the laboratory, has found that restrained eaters overeat after they violate their diet. However, there has been no evidence showing that this same process occurs outside the lab. We hypothesized that outside of this artificial setting, restrained eaters would be able to control their eating. In Study 1, 127 participants reported hourly on their diet violations and eating over 2 days. In Study 2, 89 participants tracked their intake for 8 days, and 50 of these participants consumed a milk shake (a diet violation) on Day 7, as part of an ostensibly unrelated study. As hypothesized, dieters did not overeat following violations of their diet in either study. These findings are in contrast with those of previous lab studies and dispel the widely held belief that diet violations lead to overeating in everyday life.
doi:10.1111/j.1467-9280.2009.02436.x
PMCID: PMC2761536  PMID: 19732383
3.  Image Data Sharing for Biomedical Research—Meeting HIPAA Requirements for De-identification 
Journal of Digital Imaging  2011;25(1):14-24.
Data sharing is increasingly recognized as critical to cross-disciplinary research and to assuring scientific validity. Despite National Institutes of Health and National Science Foundation policies encouraging data sharing by grantees, little data sharing of clinical data has in fact occurred. A principal reason often given is the potential of inadvertent violation of the Health Insurance Portability and Accountability Act privacy regulations. While regulations specify the components of private health information that should be protected, there are no commonly accepted methods to de-identify clinical data objects such as images. This leads institutions to take conservative risk-averse positions on data sharing. In imaging trials, where images are coded according to the Digital Imaging and Communications in Medicine (DICOM) standard, the complexity of the data objects and the flexibility of the DICOM standard have made it especially difficult to meet privacy protection objectives. The recent release of DICOM Supplement 142 on image de-identification has removed much of this impediment. This article describes the development of an open-source software suite that implements DICOM Supplement 142 as part of the National Biomedical Imaging Archive (NBIA). It also describes the lessons learned by the authors as NBIA has acquired more than 20 image collections encompassing over 30 million images.
doi:10.1007/s10278-011-9422-x
PMCID: PMC3264712  PMID: 22038512
Data sharing; De-identification; Anonymization; Cross-disciplinary research; Open access; Open source; DICOM; Supplement 142; Image archive; HIPAA; PHI; Common rule
4.  Access To Essential Maternal Health Interventions and Human Rights Violations among Vulnerable Communities in Eastern Burma 
PLoS Medicine  2008;5(12):e242.
Background
Health indicators are poor and human rights violations are widespread in eastern Burma. Reproductive and maternal health indicators have not been measured in this setting but are necessary as part of an evaluation of a multi-ethnic pilot project exploring strategies to increase access to essential maternal health interventions. The goal of this study is to estimate coverage of maternal health services prior to this project and associations between exposure to human rights violations and access to such services.
Methods and Findings
Selected communities in the Shan, Mon, Karen, and Karenni regions of eastern Burma that were accessible to community-based organizations operating from Thailand were surveyed to estimate coverage of reproductive, maternal, and family planning services, and to assess exposure to household-level human rights violations within the pilot-project target population. Two-stage cluster sampling surveys among ever-married women of reproductive age (15–45 y) documented access to essential antenatal care interventions, skilled attendance at birth, postnatal care, and family planning services. Mid-upper arm circumference, hemoglobin by color scale, and Plasmodium falciparum parasitemia by rapid diagnostic dipstick were measured. Exposure to human rights violations in the prior 12 mo was recorded. Between September 2006 and January 2007, 2,914 surveys were conducted. Eighty-eight percent of women reported a home delivery for their last pregnancy (within previous 5 y). Skilled attendance at birth (5.1%), any (39.3%) or ≥ 4 (16.7%) antenatal visits, use of an insecticide-treated bed net (21.6%), and receipt of iron supplements (11.8%) were low. At the time of the survey, more than 60% of women had hemoglobin level estimates ≤ 11.0 g/dl and 7.2% were Pf positive. Unmet need for contraceptives exceeded 60%. Violations of rights were widely reported: 32.1% of Karenni households reported forced labor and 10% of Karen households had been forced to move. Among Karen households, odds of anemia were 1.51 (95% confidence interval [CI] 0.95–2.40) times higher among women reporting forced displacement, and 7.47 (95% CI 2.21–25.3) higher among those exposed to food security violations. The odds of receiving no antenatal care services were 5.94 (95% CI 2.23–15.8) times higher among those forcibly displaced.
Conclusions
Coverage of basic maternal health interventions is woefully inadequate in these selected populations and substantially lower than even the national estimates for Burma, among the lowest in the region. Considerable political, financial, and human resources are necessary to improve access to maternal health care in these communities.
Luke Mullany and colleagues examine access to essential maternal health interventions and human rights violations within vulnerable communities in eastern Burma.
Editors' Summary
Background.
After decades of military rule, Burma has one of the world's worst health-care systems and high levels of ill health. For example, maternal mortality (deaths among women from pregnancy-related causes) is around 360 per 100,000 live births in Burma, whereas in neighboring Thailand it is only 44 per 100,000 live births. Maternal health is even worse in the Shan, Karenni, Karen and Mon states in eastern Burma where ethnic conflicts and enforced village relocations have internally displaced more than half a million people. Here, maternal mortality is thought to be about 1000 per 100, 000 live births. In an effort to improve access to life-saving maternal health interventions in these states, Burmese community-based health organizations, the Johns Hopkins Center for Public Health and Human Rights and the Global Health Access Program in the USA, and the Mae Tao Clinic (a health-worker training center in Thailand) recently set up the Mobile Obstetric Maternal Health Workers (MOM) Project. In this pilot project, local health workers from 12 communities in eastern Burma received training in antenatal care, emergency obstetrics (the care of women during childbirth), blood transfusion, and family planning at the Mae Tao Clinic. Back in Burma, these maternal health workers trained additional local health workers and traditional birth attendants. All these individuals now provide maternal health care to their communities.
Why Was This Study Done?
The effectiveness of the MOM project can only be evaluated if accurate baseline information on women's access to maternal health-care services is available. This information is also needed to ensure the wise use of scarce health-care resources. However, very little is known about reproductive and maternal health in eastern Burma. In this study, the researchers analyze the information on women's access to reproductive and maternal health-care services that was collected during the initial field implementation stage of the MOM project. In addition, they analyze whether exposure to enforced village relocations and other human rights violations affect access to maternal health-care services.
What Did the Researchers Do and Find?
Trained survey workers asked nearly 3000 ever-married women of reproductive age in the selected communities about their access to antenatal and postnatal care, skilled birth attendants, and family planning. They measured each woman's mid-upper arm circumference (an indicator of nutritional status) and tested them for anemia (iron deficiency) and infection with malaria parasites (a common cause of anemia in tropical countries). Finally, they asked the women about any recent violations of their human rights such as forced labour or relocation. Nearly 90% of the women reported a home delivery for their last baby. A skilled attendant was present at only one in 20 births and only one in three women had any antenatal care. One third of the women received postnatal care and only a third said they had access to effective contraceptives. Few women had received iron supplements or had used insecticide-treated bednets to avoid malaria-carrying mosquitos. Consequently, more than half the women were anemic and 7.2% were infected with malaria parasites. Many women also showed signs of poor nutrition. Finally, human rights violations were widely reported by the women. In Karen, the region containing most of the study communities, forced relocation tripled the risk of women developing anemia and greatly decreased their chances of receiving any antenatal care.
What Do These Findings Mean?
These findings show that access to maternal health-care interventions is extremely limited and that poor nutrition, anemia, and malaria, all of which increase the risk of pregnancy complications, are widespread in the communities in the MOM project. Because these communities had some basic health services and access to training in Thailand before the project started, these results probably underestimate the lack of access to maternal health-care services in eastern Burma. Nevertheless, it is clear that considerable political, financial, and human resources will be needed to improve maternal health in this region. Finally, the findings also reveal a link between human rights violations and reduced access to maternal health-care services. Thus, the scale of human rights violations will need to be considered when evaluating programs designed to improve maternal health in Burma and in other places where there is ongoing conflict.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050242.
This research article is further discussed in a PLoS Medicine Perspective by Macaya Douoguih
The World Health Organization provides information on all aspects of health in Burma (in several languages)
The Mae Tao Clinic also provides general information about Burma and its health services
More information about the MOM project is available in a previous publication by the researchers
The Burma Campaign UK and Human Rights Watch both provide detailed information about human rights violations in Burma
The United Nations Population Fund provides information about safe motherhood and ongoing efforts to save mothers' lives around the world
doi:10.1371/journal.pmed.0050242
PMCID: PMC2605890  PMID: 19108601
5.  WAGES, WAGE VIOLATIONS, AND PESTICIDE SAFETY EXPERIENCED BY MIGRANT FARMWORKERS IN NORTH CAROLINA* 
New Solutions  2011;21(2):251-268.
Farmworkers have the potential to receive wages that fail to meet minimum wage standards. This analysis describes wages and minimum wage violations among farmworkers, and it determines associations of wage violations with personal characteristics and pesticide safety regulation violations. Data are from a cross-sectional survey of 300 eastern North Carolina farmworkers conducted in June through August, 2009. Most farmworkers (90.0%) were paid by the hour, but 11.7 percent received piece-rate pay. Wage violations were prevalent among farmworkers: 18.3 percent of all farmworkers, 45.3 percent of farmworkers without H-2A visas, and 3.6 percent of farmworkers with H-2A visas experienced wage violations. Most farmworkers experienced numerous pesticide safety violations. Personal characteristics were not associated with wage violations among farmworkers without H-2A visas, but some pesticide safety violations were associated with wage violations. The association of violations indicates that some growers generally violate regulations. Greater enforcement of all regulations is needed.
doi:10.2190/NS.21.2.h
PMCID: PMC3291018  PMID: 21733804
Occupational health; wage theft; minority health; health disparities
6.  The Impact of Regulations, Safety Considerations and Physical Limitations on Research Progress at Maximum Biocontainment 
Viruses  2012;4(12):3932-3951.
We describe herein, limitations on research at biosafety level 4 (BSL-4) containment laboratories, with regard to biosecurity regulations, safety considerations, research space limitations, and physical constraints in executing experimental procedures. These limitations can severely impact the number of collaborations and size of research projects investigating microbial pathogens of biodefense concern. Acquisition, use, storage, and transfer of biological select agents and toxins (BSAT) are highly regulated due to their potential to pose a severe threat to public health and safety. All federal, state, city, and local regulations must be followed to obtain and maintain registration for the institution to conduct research involving BSAT. These include initial screening and continuous monitoring of personnel, controlled access to containment laboratories, accurate and current BSAT inventory records. Safety considerations are paramount in BSL-4 containment laboratories while considering the types of research tools, workflow and time required for conducting both in vivo and in vitro experiments in limited space. Required use of a positive-pressure encapsulating suit imposes tremendous physical limitations on the researcher. Successful mitigation of these constraints requires additional time, effort, good communication, and creative solutions. Test and evaluation of novel vaccines and therapeutics conducted under good laboratory practice (GLP) conditions for FDA approval are prioritized and frequently share the same physical space with important ongoing basic research studies. The possibilities and limitations of biomedical research involving microbial pathogens of biodefense concern in BSL-4 containment laboratories are explored in this review.
doi:10.3390/v4123932
PMCID: PMC3528297  PMID: 23342380
biocontainment; biosafety level 4 (BSL-4); biological select agents and toxins (BSAT); positive pressure suit; biodefense; biosecurity; ebola virus; highly pathogenic viruses; limitations; collaboration
7.  Memory for Expectation-Violating Concepts: The Effects of Agents and Cultural Familiarity 
PLoS ONE  2014;9(4):e90684.
Previous research has shown that ideas which violate our expectations, such as schema-inconsistent concepts, enjoy privileged status in terms of memorability. In our study, memory for concepts that violate cultural (cultural schema-level) expectations (e.g., “illiterate teacher”, “wooden bottle”, or “thorny grass”) versus domain-level (ontological) expectations (e.g., “speaking cat”, “jumping maple”, or “melting teacher”) was examined. Concepts that violate cultural expectations, or counter-schematic, were remembered to a greater extent compared with concepts that violate ontological expectations and with intuitive concepts (e.g., “galloping pony”, “drying orchid”, or “convertible car”), in both immediate recall, and delayed recognition tests. Importantly, concepts related to agents showed a memory advantage over concepts not pertaining to agents, but this was true only for expectation-violating concepts. Our results imply that intuitive, everyday concepts are equally attractive and memorable regardless of the presence or absence of agents. However, concepts that violate our expectations (cultural-schema or domain-level) are more memorable when pertaining to agents (humans and animals) than to non-agents (plants or objects/artifacts). We conclude that due to their evolutionary salience, cultural ideas which combine expectancy violations and the involvement of an agent are especially memorable and thus have an enhanced probability of being successfully propagated.
doi:10.1371/journal.pone.0090684
PMCID: PMC3979650  PMID: 24714568
8.  Data Integration for Dynamic and Sustainable Systems Biology Resources: Challenges and Lessons Learned 
Chemistry & biodiversity  2010;7(5):1124-1141.
Systems biology and infectious disease (host-pathogen-environment) research and development is becoming increasingly dependent on integrating data from diverse and dynamic sources. Maintaining integrated resources over long periods of time presents distinct challenges. This paper describes experiences and lessons learned from integrating data in two five-year projects focused on pathosystems biology: the Pathosystems Resource Integration Center (PATRIC, http://patric.vbi.vt.edu/), with a goal of developing bioinformatics resources for the research and countermeasures development communities based on genomics data, and the Resource Center for Biodefense Proteomics Research (RCBPR, http://www.proteomicsresource.org/), with a goal of developing resources based on the experiment data such as microarray and proteomics data from diverse sources and technologies. Some challenges include integrating genomic sequence and experiment data, data synchronization, data quality control, and usability engineering. We present examples of a variety of data integration problems drawn from our experiences with PATRIC and RBPRC, as well as open research questions related to long term sustainability, and describe the next steps to meeting these challenges. Novel contributions of this work include (1) an approach for addressing discrepancies between experiment results and interpreted results and (2) expanding the range of data integration techniques to include usability engineering at the presentation level.
doi:10.1002/cbdv.200900317
PMCID: PMC2894471  PMID: 20491070
9.  Rift Valley Fever Virus Infection in African Buffalo (Syncerus caffer) Herds in Rural South Africa: Evidence of Interepidemic Transmission 
Rift Valley fever virus (RVFV) is an emerging biodefense pathogen that poses significant threats to human and livestock health. To date, the interepidemic reservoirs of RVFV are not well defined. In a longitudinal survey of infectious diseases among African buffalo during 2000–2006, 550 buffalo were tested for antibodies against RVFV in 820 capture events in 302 georeferenced locations in Kruger National Park, South Africa. Overall, 115 buffalo (21%) were seropositive. Seroprevalence of RVFV was highest (32%) in the first study year, and decreased progressively in subsequent years, but had no detectable impact on survival. Nine (7%) of 126 resampled, initially seronegative animals seroconverted during periods outside any reported regional RVFV outbreaks. Seroconversions for RVFV were detected in significant temporal clusters during 2001–2003 and in 2004. These findings highlight the potential importance of wildlife as reservoirs for RVFV and interepidemic RVFV transmission in perpetuating regional RVFV transmission risk.
doi:10.4269/ajtmh.2011.10-0187
PMCID: PMC3062463  PMID: 21460024
10.  A Group Motivational Interviewing Intervention Reduces Drinking and Alcohol-Related Negative Consequences in Adjudicated College Women 
Addictive Behaviors  2007;32(11):2549-2562.
College students who violate campus alcohol policies (adjudicated students) are at high risk for experiencing negative alcohol-related consequences and for undermining campus life. Further, college women may be especially at risk due to differential intoxication effects and sexual consequences experienced mainly by female students. Research on interventions for adjudicated students, especially adjudicated females, has been limited. One hundred and fifteen college women who received a sanction for violating campus alcohol policies participated in the study. The two hour group intervention focused on female-specific reasons for drinking and included decisional balance, goal setting and other exercises. Participants completed follow-up surveys for 12 weeks following the intervention and answered questions regarding alcohol consumption and alcohol-related negative consequences. Findings support the use of an MI-based intervention to reduce both alcohol consumption and consequences among adjudicated females. Specifically, alcohol use was reduced by 29.9% and negative consequences were reduced by 35.87% from pre-intervention to 3-month follow up. Further, the intervention appeared to successfully initiate change in the heaviest drinkers, as women who drank at risky levels reduced alcohol consumption to a greater extent than women who drank at moderate levels.
doi:10.1016/j.addbeh.2007.05.014
PMCID: PMC3391164  PMID: 17628347
adjudicated college students; motivational interviewing; female; college drinking
11.  The Relationship Between Procrastination, Learning Strategies and Statistics Anxiety Among Iranian College Students: A Canonical Correlation Analysis 
Objective: Approximately 66-80%of graduate students experience statistics anxiety and some researchers propose that many students identify statistics courses as the most anxiety-inducing courses in their academic curriculums. As such, it is likely that statistics anxiety is, in part, responsible for many students delaying enrollment in these courses for as long as possible. This paper proposes a canonical model by treating academic procrastination (AP), learning strategies (LS) as predictor variables and statistics anxiety (SA) as explained variables.
Methods: A questionnaire survey was used for data collection and 246-college female student participated in this study. To examine the mutually independent relations between procrastination, learning strategies and statistics anxiety variables, a canonical correlation analysis was computed.
Results: Findings show that two canonical functions were statistically significant. The set of variables (metacognitive self-regulation, source management, preparing homework, preparing for test and preparing term papers) helped predict changes of statistics anxiety with respect to fearful behavior, Attitude towards math and class, Performance, but not Anxiety.
Conclusion: These findings could be used in educational and psychological interventions in the context of statistics anxiety reduction.
PMCID: PMC3939948  PMID: 24644468
learning strategies; Procrastination; Self-regulation; statistics anxiety
12.  Statistical Approach To Estimate Vaccinia-Specific Neutralizing Antibody Titers Using a High-Throughput Assay▿  
Because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. One avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. Here we describe the adaptation of a β-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. We also describe the statistical methods involved in analyzing the large quantity of data generated. The assay and its associated methods should prove useful tools in monitoring immune responses to next-generation smallpox vaccines, studying poxvirus immunity, and evaluating therapeutic agents such as vaccinia virus immune globulin.
doi:10.1128/CVI.00109-09
PMCID: PMC2725542  PMID: 19535540
13.  The Seattle Structural Genomics Center for Infectious Disease (SSGCID) 
The NIAID-funded Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium established to apply structural genomics approaches to potential drug targets from NIAID priority organisms for biodefense and emerging and re-emerging diseases. The mission of the SSGCID is to determine ~400 protein structures over five years ending in 2012. In order to maximize biomedical impact, ligand-based drug-lead discovery campaigns will be pursued for a small number of high-impact targets. Here we review the center’s target selection processes, which include pro-active engagement of the infectious disease research and drug therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. This is followed by a brief overview of the SSGCID structure determination pipeline and ligand screening methodology. Finally, specifics of our resources available to the scientific community are presented. Physical materials and data produced by SSGCID will be made available to the scientific community, with the aim that they will provide essential groundwork benefiting future research and drug discovery.
PMCID: PMC2857597  PMID: 19594426
structure-based drug development; structural genomics; biodefense; ligand screening; SSGCID
14.  Melioidosis Vaccines: A Systematic Review and Appraisal of the Potential to Exploit Biodefense Vaccines for Public Health Purposes 
Background
Burkholderia pseudomallei is a Category B select agent and the cause of melioidosis. Research funding for vaccine development has largely considered protection within the biothreat context, but the resulting vaccines could be applicable to populations who are at risk of naturally acquired melioidosis. Here, we discuss target populations for vaccination, consider the cost-benefit of different vaccination strategies and review potential vaccine candidates.
Methods and Findings
Melioidosis is highly endemic in Thailand and northern Australia, where a biodefense vaccine might be adopted for public health purposes. A cost-effectiveness analysis model was developed, which showed that a vaccine could be a cost-effective intervention in Thailand, particularly if used in high-risk populations such as diabetics. Cost-effectiveness was observed in a model in which only partial immunity was assumed. The review systematically summarized all melioidosis vaccine candidates and studies in animal models that had evaluated their protectiveness. Possible candidates included live attenuated, whole cell killed, sub-unit, plasmid DNA and dendritic cell vaccines. Live attenuated vaccines were not considered favorably because of possible reversion to virulence and hypothetical risk of latent infection, while the other candidates need further development and evaluation. Melioidosis is acquired by skin inoculation, inhalation and ingestion, but routes of animal inoculation in most published studies to date do not reflect all of this. We found a lack of studies using diabetic models, which will be central to any evaluation of a melioidosis vaccine for natural infection since diabetes is the most important risk factor.
Conclusion
Vaccines could represent one strand of a public health initiative to reduce the global incidence of melioidosis.
Author Summary
The designation of Burkholderia pseudomallei as a category B select agent has resulted in considerable research funding to develop a protective vaccine. This bacterium also causes a naturally occurring disease (melioidosis), an important cause of death in many countries including Thailand and Australia. In this study, we explored whether a vaccine could be used to provide protection from melioidosis. An economic evaluation based on its use in Thailand indicated that a vaccine could be a cost-effective intervention if used in high-risk populations such as diabetics and those with chronic kidney or lung disease. A literature search of vaccine studies in animal models identified the current candidates, but noted that models failed to take account of the common routes of infection in natural melioidosis and major risk factors for infection, primarily diabetes. This review highlights important areas for future research if biodefence-driven vaccines are to play a role in reducing the global incidence of melioidosis.
doi:10.1371/journal.pntd.0001488
PMCID: PMC3269417  PMID: 22303489
15.  Health and Human Rights in Chin State, Western Burma: A Population-Based Assessment Using Multistaged Household Cluster Sampling 
PLoS Medicine  2011;8(2):e1001007.
Sollom and colleagues report the findings from a household survey study carried out in Western Burma; they report a high prevalence of human rights violations such as forced labor, food theft, forced displacement, beatings, and ethnic persecution.
Background
The Chin State of Burma (also known as Myanmar) is an isolated ethnic minority area with poor health outcomes and reports of food insecurity and human rights violations. We report on a population-based assessment of health and human rights in Chin State. We sought to quantify reported human rights violations in Chin State and associations between these reported violations and health status at the household level.
Methods and Findings
Multistaged household cluster sampling was done. Heads of household were interviewed on demographics, access to health care, health status, food insecurity, forced displacement, forced labor, and other human rights violations during the preceding 12 months. Ratios of the prevalence of household hunger comparing exposed and unexposed to each reported violation were estimated using binomial regression, and 95% confidence intervals (CIs) were constructed. Multivariate models were done to adjust for possible confounders. Overall, 91.9% of households (95% CI 89.7%–94.1%) reported forced labor in the past 12 months. Forty-three percent of households met FANTA-2 (Food and Nutrition Technical Assistance II project) definitions for moderate to severe household hunger. Common violations reported were food theft, livestock theft or killing, forced displacement, beatings and torture, detentions, disappearances, and religious and ethnic persecution. Self reporting of multiple rights abuses was independently associated with household hunger.
Conclusions
Our findings indicate widespread self-reports of human rights violations. The nature and extent of these violations may warrant investigation by the United Nations or International Criminal Court.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
More than 60 years after the adoption of the Universal Declaration of Human Rights, thousands of people around the world are still deprived of their basic human rights—life, liberty, and security of person. In many countries, people live in fear of arbitrary arrest and detention, torture, forced labor, religious and ethnic persecution, forced displacement, and murder. In addition, ongoing conflicts and despotic governments deprive them of the ability to grow sufficient food (resulting in food insecurity) and deny them access to essential health care. In Burma, for example, the military junta, which seized power in 1962, frequently confiscates land unlawfully, demands forced labor, and uses violence against anyone who protests. Burma is also one of the world's poorest countries in terms of health indicators. Its average life expectancy is 54 years, its maternal mortality rate (380 deaths among women from pregnancy-related causes per 100,000 live births) is nearly ten times higher than that of neighboring Thailand, and its under-five death rate (122/1000 live births) is twice that of nearby countries. Moreover, nearly half of Burmese children under 5 are stunted, and a third of young children are underweight, indicators of malnutrition in a country that, on paper, has a food surplus.
Why Was This Study Done?
Investigators are increasingly using population-based methods to quantify the associations between human rights violations and health outcomes. In eastern Burma, for example, population-based research has recently revealed a link between human rights violations and reduced access to maternal health-care services. In this study, the researchers undertake a population-based assessment of health and human rights in Chin State, an ethnic minority area in western Burma where multiple reports of human rights abuses have been documented and from which thousands of people have fled. In particular, the researchers investigate correlations between household hunger and household experiences of human rights violations—food security in Chin State is affected by periodic expansions of rat populations that devastate crop yields, by farmers being forced by the government to grow an inedible oil crop (jatropha), and by the Burmese military regularly stealing food and livestock.
What Did the Researchers Do and Find?
Local surveyors questioned the heads of randomly selected households in Chin State about their household's access to health care and its health status, and about forced labor and other human rights violations experienced by the household during the preceding 12 months. They also asked three standard questions about food availability, the answers to which were combined to provide a measure of household hunger. Of the 621 households interviewed, 91.9% reported at least one episode of a household member being forced to work in the preceding 12 months. The Burmese military imposed two-thirds of these forced labor demands. Other human rights violations reported included beating or torture (14.8% of households), religious or ethnic persecutions (14.1% of households), and detention or imprisonment of a family member (5.9% of households). Forty-three percent of the households met the US Agency for International Development Food and Nutrition Technical Assistance (FANTA) definition for moderate to severe household hunger, and human rights violations related to food insecurity were common. For example, more than half the households were forced to give up food out of fear of violence. A statistical analysis of these data indicated that the prevalence of household hunger was 6.51 times higher in households that had experienced three food-related human rights violations than in households that had not experienced such violations.
What Do These Findings Mean?
These findings quantify the extent to which the Chin ethnic minority in Burma is subjected to multiple human rights violations and indicate the geographical spread of these abuses. Importantly, they show that the health impacts of human rights violations in Chin State are substantial. In addition, they suggest that the indirect health outcomes of human rights violations probably dwarf the mortality from direct killings. Although this study has some limitations (for example, surveyors had to work in secret and it was not safe for them to collect biological samples that could have given a more accurate indication of the health status of households than questions alone), these findings should encourage the international community to intensify its efforts to reduce human rights violations in Burma.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001007.
The UN Universal Declaration of Human Rights is available in numerous languages
The Burma Campaign UK and Human Rights Watch provide detailed information about human rights violations in Burma (in several languages)
The World Health Organization provides information on health in Burma and on human rights (in several languages)
The Mae Tao clinic also provides general information about Burma and its health services (including some information in Thai)
A PLoS Medicine Research Article by Luke Mullany and colleagues provides data on human rights violations and maternal health in Burma
The Chin Human Rights Organization is working to protect and promote the rights of the Chin people
The Global Health Access Program (GHAP) provides information on health in Burma
FANTA works to improve nutrition and global food security policies
doi:10.1371/journal.pmed.1001007
PMCID: PMC3035608  PMID: 21346799
16.  Yersinia pestis Evolution on a Small Timescale: Comparison of Whole Genome Sequences from North America 
PLoS ONE  2007;2(8):e770.
Background
Yersinia pestis, the etiologic agent of plague, was responsible for several devastating epidemics throughout history and is currently of global importance to current public heath and biodefense efforts. Y. pestis is widespread in the Western United States. Because Y. pestis was first introduced to this region just over 100 years ago, there has been little time for genetic diversity to accumulate. Recent studies based upon single nucleotide polymorphisms have begun to quantify the genetic diversity of Y. pestis in North America.
Methodology/Principal Findings
To examine the evolution of Y. pestis in North America, a gapped genome sequence of CA88-4125 was generated. Sequence comparison with another North American Y. pestis strain, CO92, identified seven regions of difference (six inversions, one rearrangement), differing IS element copy numbers, and several SNPs.
Conclusions/Significance
The relatively large number of inverted/rearranged segments suggests that North American Y. pestis strains may be undergoing inversion fixation at high rates over a short time span, contributing to higher-than-expected diversity in this region. These findings will hopefully encourage the scientific community to sequence additional Y. pestis strains from North America and abroad, leading to a greater understanding of the evolutionary history of this pathogen.
doi:10.1371/journal.pone.0000770
PMCID: PMC1940323  PMID: 17712418
17.  A Francisella tularensis Locus Required for Spermine Responsiveness Is Necessary for Virulence ▿  
Infection and Immunity  2011;79(9):3665-3676.
Tularemia is a debilitating febrile illness caused by the category A biodefense agent Francisella tularensis. This pathogen infects over 250 different hosts, has a low infectious dose, and causes high morbidity and mortality. Our understanding of the mechanisms by which F. tularensis senses and adapts to host environments is incomplete. Polyamines, including spermine, regulate the interactions of F. tularensis with host cells. However, it is not known whether responsiveness to polyamines is necessary for the virulence of the organism. Through transposon mutagenesis of F. tularensis subsp. holarctica live vaccine strain (LVS), we identified FTL_0883 as a gene important for spermine responsiveness. In-frame deletion mutants of FTL_0883 and FTT_0615c, the homologue of FTL_0883 in F. tularensis subsp. tularensis Schu S4 (Schu S4), elicited higher levels of cytokines from human and murine macrophages compared to wild-type strains. Although deletion of FTL_0883 attenuated LVS replication within macrophages in vitro, the Schu S4 mutant with a deletion in FTT_0615c replicated similarly to wild-type Schu S4. Nevertheless, both the LVS and the Schu S4 mutants were significantly attenuated in vivo. Growth and dissemination of the Schu S4 mutant was severely reduced in the murine model of pneumonic tularemia. This attenuation depended on host responses to elevated levels of proinflammatory cytokines. These data associate responsiveness to polyamines with tularemia pathogenesis and define FTL_0883/FTT_0615c as an F. tularensis gene important for virulence and evasion of the host immune response.
doi:10.1128/IAI.00135-11
PMCID: PMC3165480  PMID: 21670171
18.  Violated Wishes About Division of Childcare Labor Predict Early Coparenting Process During Stressful and Nonstressful Family Evaluations 
Infant mental health journal  2008;29(4):343-361.
Prior research has indicated that expectant parents overestimate the extent to which fathers will take part in the “work” of parenting, with mothers often becoming disenchanted when these expectations are violated following the baby’s arrival. In this study, we examine the role of violated wishes concerning childcare involvement in accounting for variability in maternal and paternal marital satisfaction, and in early coparenting behavior as assessed during family-interaction sessions. The results indicate possible negative effects of violated wishes on the enacted family process and confirm previous findings regarding the effects of marital satisfaction. In addition, we uncovered differences in the way that violated maternal wishes are related to coparenting during playful and mildly stressful family interactions.
doi:10.1002/imhj.20183
PMCID: PMC2746667  PMID: 19768138
19.  Transitivity in health utility measurement: An experimental analysis 
Several experimental studies have observed substantial violations of transitivity for decisions between risky lotteries over monetary outcomes. The goal of our experiment is to test whether these violations also affect the evaluation of health states. A particular feature of our experimental design is that it takes into account the possible role of decision errors for generating violations of transitivity. Since we find neither substantial nor systematic deviations from transitive choice behaviour, we can conclude that previously reported violations do not seem to bias health utility measurement.
doi:10.1186/2191-1991-1-12
PMCID: PMC3403338  PMID: 22827845
Transitivity; health utility; errors
20.  BEI Resources: Supporting antiviral research 
Antiviral research  2008;80(2):102-106.
The Biodefense and Emerging Infections Research Resources Repository (BEI Resources) provides unique, quality-assured reagents to the scientific community for use in basic research and product development involving biodefense and emerging infectious diseases. These include microorganisms (up to Biosafety Level-3) on the National Institute of Allergy and Infectious Diseases (NIAID) and Centers for Disease Control and Prevention (CDC) lists of Category A, B and C priority pathogens. In addition to live microorganisms, related products such as polyclonal antisera, monoclonal antibodies, isolated nucleic acid preparations, overlapping peptide arrays, purified proteins, and assay kits are also available. Many of these materials have direct or indirect applications in antiviral research. These reagents are available free of charge to all registered investigators, regardless of funding source or affiliation. Acquisition of new reagents for the repository is one of the critically necessary and challenging tasks for BEI Resources. Therefore, investigators are encouraged to deposit relevant items, so as to provide access to materials, relief from the burden of distribution, protection of intellectual property rights, and secure storage. In addition, BEI Resources has the capability of contracting for the preparation of specific reagents. If there is a resource needed to advance a specific research area, contact an NIAID program officer or use the “suggest a reagent” option on the BEI Resources homepage, www.beiresources.org.
doi:10.1016/j.antiviral.2008.07.003
PMCID: PMC2614313  PMID: 18675849
biodefense; emerging infectious disease; repository; reagents; culture collection; antiviral therapy
21.  A renewed, ethical defense of placebo-controlled trials of new treatments for major depression and anxiety disorders 
Journal of medical ethics  2009;35(6):384-389.
The use of placebo as a control condition in clinical trials of major depressive disorder and anxiety disorders continues to be an area of ethical concern. Typically, opponents of placebo controls argue that they violate the beneficent-based, “best proven diagnostic and therapeutic method” that the original Helsinki Declaration of 1964 famously asserted participants are owed. A more consequentialist, oppositional argument is that participants receiving placebo might suffer enormously by being deprived of their usual medication(s). Nevertheless, recent findings of potential for suicidality in young people treated with antidepressants, along with meta-analyses suggesting that antidepressants add no significant clinical benefit over placebos, warrant a re-evaluation of the arguments against placebo. Furthermore, the nature of placebo treatment in short-term clinical trials is often not well understood, and lack of understanding can foster opposition to it. This paper will show how scientific justifications for placebo use are morally relevant. The fundamental ethical importance of placebo controls is discussed in relation to several aspects of clinical trials, including detection of adverse events, accurate assessment of clinical benefit, advancing understanding of the heterogeneity of depression and anxiety disorders and respecting informed consent requirements. Prohibiting the use of placebo controls is morally concerning in that such prohibitions allow for the possibility of serious adverse public health consequences. Moral worries that research participants receiving placebo are being unduly jeopardised will be shown to be exaggerated, especially in relation to the net benefits for end-users to be gained from the quality of data resulting from using placebo controls.
doi:10.1136/jme.2008.028357
PMCID: PMC3711824  PMID: 19482985
22.  Real-Time PCR Assay for Detection of a New Simulant for Poxvirus Biothreat Agents▿  
Research and financial efforts spent on biodefense technologies highlight the current concern for biothreat event preparedness. Nonhazardous but relevant “simulant” microorganisms are typically used to simplify technological developments, testing, and staff training. The bacteriophage MS2, a small RNA virus, is classically used as the reference simulant for biothreat viruses within the biodefense community. However, variola virus, considered a major threat, displays very different features (size, envelope, and double-stranded DNA genome). The size parameter is critical for aerosol sampling, detection, and protection/filtration technologies. Therefore, a panel of relevant simulants should be used to cover the diversity of biothreat agents. Thus, we investigated a new virus model, the Cydia pomonella granulovirus (baculovirus), which is currently used as a biopesticide. It displays a size similar to that of poxviruses, is enveloped, and contains double-stranded DNA. To provide a molecular tool to detect and quantify this model virus, we developed an assay based on real-time PCR, with a limit of detection ranging from roughly 10 to a few tens of target copies per μl according to the sample matrix. The specificity of the assay against a large panel of potential cross-reactive microorganisms was checked, and the suitability of the assay for environmental samples, especially aerosol studies, was determined. In conclusion, we suggest that our PCR assay allows Cydia pomonella granulovirus to be used as a simulant for poxviruses. This assay may also be useful for environmental or crop treatment studies.
doi:10.1128/AEM.02120-08
PMCID: PMC2655438  PMID: 19168659
23.  Occurrence of Sulfa Drug Residues in Canadian Pork Liver 
The Canadian Veterinary Journal  1985;26(9):282-284.
Sulfonamide residues in the livers of wholesome carcasses of Canadian pork were monitored over the six year period ending March 31, 1985. The annual rate of violative residues decreased from 9.92% to 2.75% over the course of the six years. At present the incidence of violation in the livers is 2.35% and there is no significant difference within the various regions of Canada. This would result in a muscle violative rate of 0.8%.
The only sulfonamide found at violative levels was sulfamethazine. All violative samples were within the range 0.11-4.00 ppm. Over the period of the survey the incidence of violations at all levels decreased. Violations at higher levels decreased most rapidly resulting in a continuous reduction of the mean level in violative samples.
PMCID: PMC1680107  PMID: 17422573
Drug residues; sulfonamide residues; pork liver; sulfamethazine
24.  Review and Recommendations for Zero-inflated Count Regression Modeling of Dental Caries Indices in Epidemiological Studies 
Caries research  2012;46(4):413-423.
Over the past five to ten years, zero-inflated count regression models have been increasingly applied to the analysis of dental caries indices (e.g., DMFT, dfms, etc). The main reason for that is linked to the broad decline in children’s caries experience, such that dmf and DMF indices more frequently generate low or even zero counts. This article specifically reviews the application of zero-inflated Poisson and zero-inflated negative binomial regression models to dental caries, with emphasis on the description of the models and the interpretation of fitted model results given the study goals. The review finds that interpretations provided in the published caries research are often imprecise or inadvertently misleading, particularly with respect to failing to discriminate between inference for the class of susceptible persons defined by such models and inference for the sampled population in terms of overall exposure effects. Recommendations are provided to enhance the use as well as the interpretation and reporting of results of count regression models when applied to epidemiological studies of dental caries.
doi:10.1159/000338992
PMCID: PMC3424072  PMID: 22710271
dental caries; excess zeros; incidence; increment; overdispersion; prevalence
25.  Migrant Farmworker Housing Regulation Violations in North Carolina 
Background
The quality of housing provided to migrant farmworkers is often criticized, but few studies have investigated these housing conditions. This analysis examines housing regulation violations experienced by migrant farmworkers in North Carolina, and the associations of camp characteristics with the presence of housing violations.
Methods
Data were collected in183 eastern North Carolina migrant farmworker camps in 2010. Housing regulation violations for the domains of camp, sleeping room, bathroom, kitchen, laundry room, and general housing, as well as total violations were assessed using North Carolina Department of Labor standards.
Results
Violations of housing regulations were common, ranging from 4 to 22 per camp. Housing regulation violations were common in all domains; the mean number of camp violations was 1.6, of sleeping room violations was 3.8, of bathroom violations was 4.5, of kitchen violations was 2.3, of laundry room violations was 1.2, and of general housing violations was 3.1. The mean number of total housing violations was 11.4. Several camp characteristics were consistently associated with the number of violations; camps with workers having H-2A visas, with North Carolina Department of Labor Certificates of Inspection posted, and assessed early in the season had fewer violations.
Conclusions
These results argue for regulatory changes to improve the quality of housing provided to migrant farmworkers, including stronger regulations and the more vigorous enforcement of existing regulations.
doi:10.1002/ajim.22011
PMCID: PMC3708262  PMID: 22237961
Migrant farmworker; housing conditions; substandard housing; housing standards; enforcement

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