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1.  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
2.  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
3.  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
4.  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
5.  Cross-Over between Discrete and Continuous Protein Structure Space: Insights into Automatic Classification and Networks of Protein Structures 
PLoS Computational Biology  2009;5(3):e1000331.
Structural classifications of proteins assume the existence of the fold, which is an intrinsic equivalence class of protein domains. Here, we test in which conditions such an equivalence class is compatible with objective similarity measures. We base our analysis on the transitive property of the equivalence relationship, requiring that similarity of A with B and B with C implies that A and C are also similar. Divergent gene evolution leads us to expect that the transitive property should approximately hold. However, if protein domains are a combination of recurrent short polypeptide fragments, as proposed by several authors, then similarity of partial fragments may violate the transitive property, favouring the continuous view of the protein structure space. We propose a measure to quantify the violations of the transitive property when a clustering algorithm joins elements into clusters, and we find out that such violations present a well defined and detectable cross-over point, from an approximately transitive regime at high structure similarity to a regime with large transitivity violations and large differences in length at low similarity. We argue that protein structure space is discrete and hierarchic classification is justified up to this cross-over point, whereas at lower similarities the structure space is continuous and it should be represented as a network. We have tested the qualitative behaviour of this measure, varying all the choices involved in the automatic classification procedure, i.e., domain decomposition, alignment algorithm, similarity score, and clustering algorithm, and we have found out that this behaviour is quite robust. The final classification depends on the chosen algorithms. We used the values of the clustering coefficient and the transitivity violations to select the optimal choices among those that we tested. Interestingly, this criterion also favours the agreement between automatic and expert classifications. As a domain set, we have selected a consensus set of 2,890 domains decomposed very similarly in SCOP and CATH. As an alignment algorithm, we used a global version of MAMMOTH developed in our group, which is both rapid and accurate. As a similarity measure, we used the size-normalized contact overlap, and as a clustering algorithm, we used average linkage. The resulting automatic classification at the cross-over point was more consistent than expert ones with respect to the structure similarity measure, with 86% of the clusters corresponding to subsets of either SCOP or CATH superfamilies and fewer than 5% containing domains in distinct folds according to both SCOP and CATH. Almost 15% of SCOP superfamilies and 10% of CATH superfamilies were split, consistent with the notion of fold change in protein evolution. These results were qualitatively robust for all choices that we tested, although we did not try to use alignment algorithms developed by other groups. Folds defined in SCOP and CATH would be completely joined in the regime of large transitivity violations where clustering is more arbitrary. Consistently, the agreement between SCOP and CATH at fold level was lower than their agreement with the automatic classification obtained using as a clustering algorithm, respectively, average linkage (for SCOP) or single linkage (for CATH). The networks representing significant evolutionary and structural relationships between clusters beyond the cross-over point may allow us to perform evolutionary, structural, or functional analyses beyond the limits of classification schemes. These networks and the underlying clusters are available at http://ub.cbm.uam.es/research/ProtNet.php
Author Summary
Making order of the fast-growing information on proteins is essential for gaining evolutionary and functional knowledge. The most successful approaches to this task are based on classifications of protein structures, such as SCOP and CATH, which assume a discrete view of the protein structure space as a collection of separated equivalence classes (folds). However, several authors proposed that protein domains should be regarded as assemblies of polypeptide fragments, which implies that the protein–structure space is continuous. Here, we assess these views of domain space through the concept of transitivity; i.e., we test whether structure similarity of A with B and B with C implies that A and C are similar, as required for consistent classification. We find that the domain space is approximately transitive and discrete at high similarity and continuous at low similarity, where transitivity is severely violated. Comparing our classification at the cross-over similarity with CATH and SCOP, we find that they join proteins at low similarity where classification is inconsistent. Part of this discrepancy is due to structural divergence of homologous domains, which are forced to be in a single cluster in CATH and SCOP. Structural and evolutionary relationships between consistent clusters are represented as a network in our approach, going beyond current protein classification schemes. We conjecture that our results are related to a change of evolutionary regime, from uniparental divergent evolution for highly related domains to assembly of large fragments for which the classical tree representation is unsuitable.
doi:10.1371/journal.pcbi.1000331
PMCID: PMC2654728  PMID: 19325884
6.  Medical Evidence of Human Rights Violations against Non-Arabic-Speaking Civilians in Darfur: A Cross-Sectional Study 
PLoS Medicine  2012;9(4):e1001198.
Alexander Tsai and colleagues review medical records from the Amel Centre, Sudan, to assess consistency between recorded medical evidence and patient reports of human rights violations by the Government of Sudan and Janjaweed forces.
Background
Ongoing conflict in the Darfur region of Sudan has resulted in a severe humanitarian crisis. We sought to characterize the nature and geographic scope of allegations of human rights violations perpetrated against civilians in Darfur and to evaluate their consistency with medical examinations documented in patients' medical records.
Methods and Findings
This was a retrospective review and analysis of medical records from all 325 patients seen for treatment from September 28, 2004, through December 31, 2006, at the Nyala-based Amel Centre for Treatment and Rehabilitation of Victims of Torture, the only dedicated local provider of free clinical and legal services to civilian victims of torture and other human rights violations in Darfur during this time period. Among 325 medical records identified and examined, 292 (89.8%) patients from 12 different non-Arabic-speaking tribes disclosed in the medical notes that they had been attacked by Government of Sudan (GoS) and/or Janjaweed forces. Attacks were reported in 23 different rural council areas throughout Darfur. Nearly all attacks (321 [98.8%]) were described as having occurred in the absence of active armed conflict between Janjaweed/GoS forces and rebel groups. The most common alleged abuses were beatings (161 [49.5%]), gunshot wounds (140 [43.1%]), destruction or theft of property (121 [37.2%]), involuntary detainment (97 [29.9%]), and being bound (64 [19.7%]). Approximately one-half (36 [49.3%]) of all women disclosed that they had been sexually assaulted, and one-half of sexual assaults were described as having occurred in close proximity to a camp for internally displaced persons. Among the 198 (60.9%) medical records that contained sufficient detail to enable the forensic medical reviewers to render an informed judgment, the signs and symptoms in all of the medical records were assessed to be consistent with, highly consistent with, or virtually diagnostic of the alleged abuses.
Conclusions
Allegations of widespread and sustained torture and other human rights violations by GoS and/or Janjaweed forces against non-Arabic-speaking civilians were corroborated by medical forensic review of medical records of patients seen at a local non-governmental provider of free clinical and legal services in Darfur. Limitations of this study were that patients seen in this clinic may not have been a representative sample of persons alleging abuse by Janjaweed/GoS forces, and that most delayed presenting for care. The quality of documentation was similar to that available in other conflict/post-conflict, resource-limited settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Conflict in the Darfur region of Sudan between Arabic- and non-Arabic-speaking tribes over the past decade has resulted in a severe humanitarian crisis. According to the United Nations, more than 2.7 million people have fled from their homes to camps for internally displaced persons (IDPs) or to refugee camps in neighboring Chad, and up to 300,000 people have died from war, hunger, and disease since the conflict started. The origins of this conflict go back many years, but in 2003, organized rebel forces began attacking government targets, accusing the Government of Sudan (GoS) of oppressing black Africans in favor of Arabs. In response, the GoS attacked the rebel forces, but some observers allege it also targeted non-Arabic-speaking civilians, in contravention of international laws of war. Observers have also accused the GoS of having links with the Janjaweed militias, nomadic Arabs who attack settled black farmers, although the GoS denies any such links. Indeed, reports of systematic, targeted assaults on non-Arabic-speaking civilians, of large-scale disruption of rural livelihoods, and of deliberate consignment to living conditions likely to cause death have prompted some observers to accuse the GoS of genocide (violent crimes committed against a national, ethnical, racial, or religious group with the intention of destroying that group) and the International Criminal Court to issue arrest warrants for the allegedly responsible authorities.
Why Was This Study Done?
Most investigations of claims of violence against civilians in Darfur have relied on self-reported data gathered from people living in refugee camps outside Sudan. Because these data could be biased, in this cross-sectional study (a study that characterizes a population at a single point in time), the researchers investigate the nature and geographic scope of alleged abuses against civilians in Darfur and endeavor to substantiate these allegations by analyzing the medical records of patients attending the Amel Centre for Treatment and Rehabilitation of Victims of Torture in Nyala, South Darfur. Opened in 2004, this center provided free clinical and legal services to civilians affected by human rights violations. Its staff fled in 2009 because of increasingly dangerous working conditions; the medical records used in this study were sent out of Sudan before the staff fled.
What Did the Researchers Do and Find?
Between September 28, 2004, and December 31, 2006, 325 patients were seen at the Amel Centre. According to their medical records, 292 patients from 12 different non-Arabic-speaking tribes alleged that they had been attacked by GoS or Janjaweed forces in rural areas across Darfur. Nearly all the patients reported that they had been attacked in the absence of active armed conflict between GoS/Janjaweed forces and rebel groups. Half of them claimed that they had been beaten, two-fifths reported gunshot wounds, a third reported destruction or theft of property, and nearly a third reported involuntary detainment. Half of the 73 women seen at the center disclosed that they had been sexually assaulted, often near IDP camps. Only 198 medical records contained sufficient detail to enable the researchers to determine whether the documented medical evidence was consistent with the alleged abuses. However, in all these cases, the researchers judged that the medical evidence was consistent with, highly consistent with, or virtually diagnostic of the alleged abuses.
What Do These Findings Mean?
These findings provide credible medical evidence that is consistent with torture and other human rights violations being inflicted on non-Arabic-speaking civilians in Darfur from 2004 to 2006. These findings cannot be used to estimate the population incidence of attacks on civilians or to corroborate claims of assailants' identities or of genocidal intent. Moreover, their accuracy may be affected by several limitations of this study. For example, during the study period, only patients who obtained a medical evidence form from the police were permitted to receive treatment from an authorized medical officer; obtaining such a form likely represented a considerable hurdle to accessing health care services. Nevertheless, the widespread, organized, and sustained pattern of attacks documented in this study is consistent with the possibility that the actions of Janjaweed and GoS forces during the conflict in Darfur may constitute war crimes, crimes against humanity, and/or acts of genocide. Importantly, these findings also highlight the need to provide adequate protection for health professionals working in countries affected by internal conflicts.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001198.
The African UnionUnited Nations Mission in Darfur (UNAMID) provides background information and up-to-date news about the ongoing conflict in Darfur Amnesty International, which campaigns for human rights, provides background information and news about the current situation in Darfur
The Save Dafur Coalition also provides detailed information about the situation in Darfur Physicians for Human Rights, a non-profit organization that mobilizes health professionals to advance health, dignity, and justice, is calling for security in Darfur and compensation and restitution for survivors of the conflict
Wikipedia has pages on Darfur and on genocide (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Details on warrants of arrest issued by the International Criminal Court in response to the situation in Dafur are available
doi:10.1371/journal.pmed.1001198
PMCID: PMC3317898  PMID: 22509136
7.  Monitoring compliance with the International Code of Marketing of Breastmilk Substitutes in west Africa: multisite cross sectional survey in Togo and Burkina Faso 
BMJ : British Medical Journal  2003;326(7381):127.
Objectives
To monitor compliance with the International Code of Marketing of Breastmilk Substitutes in health systems, sales outlets, distribution points, and the news media in Togo and Burkina Faso, west Africa.
Design
Multisite cross sectional survey.
Participants
Staff at 43 health facilities and 66 sales outlets and distribution points, 186 health providers, and 105 mothers of infants aged ⩽5 months in 16 cities.
Results
Six (14%) health facilities had received donations of breast milk substitutes. All donations were being given to mothers free of charge. Health providers in five (12%) health facilities had received free samples of breast milk substitutes for purposes other than professional research or evaluation. Health professionals in five (12%) health facilities had received promotional gifts from manufacturers. Promotional materials of commercial breast milk substitutes were found in seven (16%) health facilities. Special displays to market commercial breast milk substitutes were found in 29 (44%) sales and distribution points. Forty commercial breast milk substitutes violated the labelling standards of the code: 21 were manufactured by Danone, 11 by Nestlé, and eight by other national and international manufacturers. Most (148, 90%) health providers had never heard of the code, and 66 mothers (63%) had never received any counselling on breast feeding by their health providers.
Conclusion
In west Africa manufacturers are violating the code of marketing of breast milk substitutes. Comparable levels of code violations are observed with (Burkina Faso) or without (Togo) regulating legislation. Legislation must be accompanied by effective information, training, and monitoring systems to ensure that healthcare providers and manufacturers comply with evidence based practice and the code.
What is already known on this topicAll member states of the World Health Assembly have reaffirmed their support for the International Code of Marketing of Breastmilk SubstitutesViolations by manufacturers of breast milk substitutes have been reported in industrialised and developing countriesWhat this study addsManufacturers of breast milk substitutes are violating the code in Togo and Burkina FasoThe levels of code violations are similar in a country with (Burkina Faso) and one without (Togo) legislation on the marketing of breast milk substitutesLegislation must be accompanied by effective information, training, and monitoring systems to ensure compliance with the code
PMCID: PMC140002  PMID: 12531842
8.  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
9.  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
10.  Characterization of Clinically-Attenuated Burkholderia mallei by Whole Genome Sequencing: Candidate Strain for Exclusion from Select Agent Lists 
PLoS ONE  2008;3(4):e2058.
Background
Burkholderia mallei is an understudied biothreat agent responsible for glanders which can be lethal in humans and animals. Research with this pathogen has been hampered in part by constraints of Select Agent regulations for safety reasons. Whole genomic sequencing (WGS) is an apt approach to characterize newly discovered or poorly understood microbial pathogens.
Methodology/Principal Findings
We performed WGS on a strain of B. mallei, SAVP1, previously pathogenic, that was experimentally infected in 6 equids (4 ponies, 1 mule, 1 donkey), natural hosts, for purposes of producing antibodies. Multiple high inocula were used in some cases. Unexpectedly SAVP1 appeared to be avirulent in the ponies and mule, and attenuated in the donkey, but induced antibodies. We determined the genome sequence of SAVP1 and compared it to a strain that was virulent in horses and a human. In comparison, this phenotypic avirulent SAVP1 strain was missing multiple genes including all the animal type III secretory system (T3SS) complex of genes demonstrated to be essential for virulence in mice and hamster models. The loss of these genes in the SAVP1 strain appears to be the consequence of a multiple gene deletion across insertion sequence (IS) elements in the B. mallei genome. Therefore, the strain by itself is unlikely to revert naturally to its virulent phenotype. There were other genes present in one strain and not the other and vice-versa.
Conclusion/Significance
The discovery that this strain of B. mallei was both avirulent in the natural host ponies, and did not possess T3SS associated genes may be fortuitous to advance biodefense research. The deleted virulence-essential T3SS is not likely to be re-acquired naturally. These findings may provide a basis for exclusion of SAVP1 from the Select Agent regulation or at least discussion of what else would be required for exclusion. This exclusion could accelerate research by investigators not possessing BSL-3 facilities and facilitate the production of reagents such as antibodies without the restraints of Select Agent regulation.
doi:10.1371/journal.pone.0002058
PMCID: PMC2312325  PMID: 18446194
11.  Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure 
Lassa virus (LASV) is a significant human pathogen that is endemic to several countries in West Africa. Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. Little is known about the complex immune mechanisms governing the response to LASV or the genetic determinants of susceptibility and resistance to infection. In the study presented here, we have used a whole-genome, microarray-based approach to determine the temporal host response in the peripheral blood mononuclear cells (PBMCs) of non-human primates (NHP) following aerosol exposure to LASV. Sequential sampling over the entire disease course showed that there are strong transcriptional changes of the immune response to LASV exposure, including the early induction of interferon-responsive genes and Toll-like receptor signaling pathways. However, this increase in early innate responses was coupled with a lack of pro-inflammatory cytokine response in LASV exposed NHPs. There was a distinct lack of cytokines such as IL1β and IL23α, while immunosuppressive cytokines such as IL27 and IL6 were upregulated. Comparison of IRF/STAT1-stimulated gene expression with the viral load in LASV exposed NHPs suggests that mRNA expression significantly precedes viremia, and thus might be used for early diagnostics of the disease. Our results provide a transcriptomic survey of the circulating immune response to hemorrhagic LASV exposure and provide a foundation for biomarker identification to allow clinical diagnosis of LASV infection through analysis of the host response.
Author Summary
Lassa virus (LASV), a member of the Arenaviridae family, is a viral hemorrhagic fever causing virus endemic to several countries in West Africa with a history of sporadic importation into the United States. It has been characterized as a Category A agent, and despite the significant public health issues posed by LASV and the potential biodefense risks, little is known about the immune response to the virus. In the study presented here, we have taken an unbiased genomics approach to map the temporal host response in the peripheral blood mononuclear cells (PBMCs) of non-human primates (NHP) exposed to LASV. Gene expression patterns over the entire disease course showed that there are strong transcriptional changes of the immune response to LASV exposure, including the upregulation of Toll-like receptor signaling pathways and innate antiviral transcription factors. However, there was a lack of pro-inflammatory cytokine response in LASV exposed NHPs similar to what is seen in human disease. Our data suggests that LASV induces negative regulation of immunological events, leading to an inefficient adaptive immune response as observed in LASV-infected human patients. Our results provide a picture of the host's circulating immune response to hemorrhagic LASV exposure and demonstrate that gene expression patterns correlate with specific stages of disease progression.
doi:10.1371/journal.pntd.0002171
PMCID: PMC3636129  PMID: 23638192
12.  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
13.  Factors Influencing the Emergence and Spread of HIV Drug Resistance Arising from Rollout of Antiretroviral Pre-Exposure Prophylaxis (PrEP) 
PLoS ONE  2011;6(4):e18165.
Background
The potential for emergence and spread of HIV drug resistance from rollout of antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is an important public health concern. We investigated determinants of HIV drug resistance prevalence after PrEP implementation through mathematical modeling.
Methodology
A model incorporating heterogeneity in age, gender, sexual activity, HIV infection status, stage of disease, PrEP coverage/discontinuation, and HIV drug susceptibility, was designed to simulate the impact of PrEP on HIV prevention and drug resistance in a sub-Saharan epidemic.
Principal Findings
Analyses suggest that the prevalence of HIV drug resistance is influenced most by the extent and duration of inadvertent PrEP use in individuals already infected with HIV. Other key factors affecting drug resistance prevalence include the persistence time of transmitted resistance and the duration of inadvertent PrEP use in individuals who become infected on PrEP. From uncertainty analysis, the median overall prevalence of drug resistance at 10 years was predicted to be 9.2% (interquartile range 6.9%–12.2%). An optimistic scenario of 75% PrEP efficacy, 60% coverage of the susceptible population, and 5% inadvertent PrEP use predicts a rise in HIV drug resistance prevalence to only 2.5% after 10 years. By contrast, in a pessimistic scenario of 25% PrEP efficacy, 15% population coverage, and 25% inadvertent PrEP use, resistance prevalence increased to over 40%.
Conclusions
Inadvertent PrEP use in previously-infected individuals is the major determinant of HIV drug resistance prevalence arising from PrEP. Both the rate and duration of inadvertent PrEP use are key factors. PrEP rollout programs should include routine monitoring of HIV infection status to limit the spread of drug resistance.
doi:10.1371/journal.pone.0018165
PMCID: PMC3078109  PMID: 21525976
14.  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
15.  Pedestrian Injury and Human Behaviour: Observing Road-Rule Violations at High-Incident Intersections 
PLoS ONE  2011;6(6):e21063.
Background
Human behaviour is an obvious, yet under-studied factor in pedestrian injury. Behavioural interventions that address rule violations by pedestrians and motorists could potentially reduce the frequency of pedestrian injury. In this study, a method was developed to examine road-rule non-compliance by pedestrians and motorists. The purpose of the study was to examine the potential association between violations made by pedestrians and motorists at signalized intersections, and collisions between pedestrians and motor-vehicles. The underlying hypothesis is that high-incident pedestrian intersections are likely to vary with respect to their aetiology, and thus are likely to require individualized interventions – based on the type and rate of pedestrian and motorist violation.
Methods
High-incident pedestrian injury intersections in Vancouver, Canada were identified using geographic information systems. Road-rule violations by pedestrians and motorists were documented at each incident hotspot by a team of observers at several different time periods during the day.
Results
Approximately 9,000 pedestrians and 18,000 vehicles were observed in total. In total for all observed intersections, over 2000 (21%) pedestrians committed one of the observed pedestrian road-crossing violations, while approximately 1000 (5.9%) drivers committed one of the observed motorist violations. Great variability in road-rule violations was observed between intersections, and also within intersections at different observation periods.
Conclusions
Both motorists and pedestrians were frequently observed committing road-rule violations at signalized intersections, suggesting a potential human behavioural contribution to pedestrian injury at the study sites. These results suggest that each intersection may have unique mechanisms that contribute to pedestrian injury, and may require targeted behavioural interventions. The method described in this study provides the basis for understanding the relationship between violations and pedestrian injury risk at urban intersections. Findings could be applied to targeted prevention campaigns designed to reduce the number of pedestrian injuries at signalized intersections.
doi:10.1371/journal.pone.0021063
PMCID: PMC3115980  PMID: 21698258
16.  What Can We Conclude from Death Registration? Improved Methods for Evaluating Completeness 
PLoS Medicine  2010;7(4):e1000262.
Julie Rajaratnam and colleagues evaluate the performance of a suite of demographic methods that estimate the fraction of deaths registered and counted by civil registration systems, and identify three variants that generally perform the best.
Background
One of the fundamental building blocks for determining the burden of disease in populations is to reliably measure the level and pattern of mortality by age and sex. Where well-functioning registration systems exist, this task is relatively straightforward. Results from many civil registration systems, however, remain uncertain because of a lack of confidence in the completeness of death registration. Incomplete registration systems mean not all deaths are counted, and resulting estimates of death rates for the population are then underestimated. Death distribution methods (DDMs) are a suite of demographic methods that attempt to estimate the fraction of deaths that are registered and counted by the civil registration system. Although widely applied and used, the methods have at least three types of limitations. First, a wide range of variants of these methods has been applied in practice with little scientific literature to guide their selection. Second, the methods have not been extensively validated in real population conditions where violations of the assumptions of the methods most certainly occur. Third, DDMs do not generate uncertainty intervals.
Methods and Findings
In this paper, we systematically evaluate the performance of 234 variants of DDM methods in three different validation environments where we know or have strong beliefs about the true level of completeness of death registration. Using these datasets, we identify three variants of the DDMs that generally perform the best. We also find that even these improved methods yield uncertainty intervals of roughly ± one-quarter of the estimate. Finally, we demonstrate the application of the optimal variants in eight countries.
Conclusions
There continues to be a role for partial vital registration data in measuring adult mortality levels and trends, but such results should only be interpreted alongside all other data sources on adult mortality and the uncertainty of the resulting levels, trends, and age-patterns of adult death considered.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Accurate worldwide information on the levels and patterns of mortality (deaths) is essential for planning and monitoring global public-health initiatives. The gold standard method for collecting such information is death registration. In high-income countries, death registration is effectively 100% complete, but the situation in many developing countries is very different. In most African countries, for example, less than one-quarter of deaths are officially recorded. Although other data sources such as household surveys can be used to estimate mortality levels in such countries, partial registration data could provide useful information about mortality levels in developing countries if its completeness could be evaluated. One way to do this is to use demographic methods called “death distribution methods” (DDMs). Demography is the study of the size, growth, and other characteristics of human populations; DDMs compare the age distribution of recorded deaths (the relative proportion of deaths in each age group) with the age distribution of the population in which they occurred to provide a correction factor that can be used to calculate corrected mortality levels from registered deaths. DDMs are used by the World Health Organization to monitor adult mortality in nearly 100 countries.
Why Was This Study Done?
Although widely used, few studies have compared the performance of the many available DDM variants, and DDMs have not been extensively validated by testing them in populations for which the completeness of death registration is known. In addition, because DDMs are mathematical in nature, they do not provide any indication of the uncertainty associated with the correction factors they yield. This means that public-health officials using estimates of mortality levels generated from partial registration data using DDMs have no idea of the limits between which the true mortality levels of their populations lie. In this study, the researchers systematically evaluate the performance of 234 DDM variants and use the optimal variants that they identify to analyze registration completeness over time in six developing countries.
What Did the Researchers Do and Find?
The researchers constructed 234 DDM variants by combining each of three general types of DDMs with 78 different “age trims”; demographers often age-trim—drop older and/or younger age groups—when using DDMs to estimate correction factors for observed death rates. The researchers then evaluated the performance of the variants in three “validation” datasets for which the completeness of death registration is known—a microsimulation of a population of 10 million people followed for 150 years, population data from US counties between 1990 and 2000, and population data from high-income OECD (Organisation for Economic Co-operation and Development) countries with populations of more than 5 million between 1950 and 2000. Detailed analyses of the performance of the DDM variants with all three datasets identified three optimal DDMs, one of each type. However, even with these optimal DDMs, the uncertainty intervals associated with estimates of relative completeness of registration were roughly +/− one-quarter of the estimate. Finally, the researchers applied their optimal DDMs to six developing countries over time. This analysis showed that death registration for adults has been relatively complete since 1970 in Mexico, for example, whereas in Tunisia, death registration has improved from nearly 50% in 1965 to complete by 1980. It also indicated that the three DDMs can give consistent results in some contexts.
What Do These Findings Mean?
By using multiple validation databases, these findings identify three optimal DDMs for the estimation of completeness of death registration. The researchers recommend that analysts apply all three methods when estimating the completeness of death registration data and look at the consistency of the results produced. They warn that the level of uncertainty associated with the estimation of completeness of registration means that results yielded by DDMs should be interpreted with considerable caution. In particular, they note that although correction factors provided by DDMs may be a good way of estimating mortality levels, the uncertainty in these factors may make them unsuitable for analyzing trends over time in mortality levels. Overall, the researchers conclude that partial death registration data have a role to play in measuring adult mortality levels, provided that they are analyzed alongside other data sources.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000262.
This study and two related PLoS Medicine Research Articles—by Obermeyer et al. and by Rajaratnam et al. —are further discussed in a PLoS Medicine Perspective by Mathers and Boerma
The Institute for Health Metrics and Evaluation makes available high-quality information on population health, its determinants, and the performance of health systems
Grand Challenges in Global Health provides information on research into better ways for developing countries to measure their health status
The World Health Organization Statistical Information System (WHOSIS) is an interactive database that brings together core health statistics for WHO member states, including information on vital registration of deaths; the WHO Health Metrics Network is a global collaboration focused on improving sources of vital statistics
doi:10.1371/journal.pmed.1000262
PMCID: PMC2854130  PMID: 20405002
17.  Perceived risk, anxiety, and behavioural responses of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands: results of three consecutive online surveys 
BMC Public Health  2011;11:2.
Background
Research into risk perception and behavioural responses in case of emerging infectious diseases is still relatively new. The aim of this study was to examine perceptions and behaviours of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands.
Methods
Two cross-sectional and one follow-up online survey (survey 1, 30 April-4 May; survey 2, 15-19 June; survey 3, 11-20 August 2009). Adults aged 18 years and above participating in a representative Internet panel were invited (survey 1, n = 456; survey 2, n = 478; follow-up survey 3, n = 934). Main outcome measures were 1) time trends in risk perception, feelings of anxiety, and behavioural responses (survey 1-3) and 2) factors associated with taking preventive measures and strong intention to comply with government-advised preventive measures in the future (survey 3).
Results
Between May and August 2009, the level of knowledge regarding Influenza A (H1N1) increased, while perceived severity of the new flu, perceived self-efficacy, and intention to comply with preventive measures decreased. The perceived reliability of information from the government decreased from May to August (62% versus 45%). Feelings of anxiety decreased from May to June, and remained stable afterwards. From June to August 2009, perceived vulnerability increased and more respondents took preventive measures (14% versus 38%). Taking preventive measures was associated with no children in the household, high anxiety, high self-efficacy, more agreement with statements on avoidance, and paying much attention to media information regarding Influenza A (H1N1). Having a strong intention to comply with government-advised preventive measures in the future was associated with higher age, high perceived severity, high anxiety, high perceived efficacy of measures, high self-efficacy, and finding governmental information to be reliable.
Conclusions
Decreasing trends over time in perceived severity and anxiety are consistent with the reality: the clinical picture of influenza turned out to be mild in course of time. Although (inter)national health authorities initially overestimated the case fatality rate, the public stayed calm and remained to have a relatively high intention to comply with preventive measures.
doi:10.1186/1471-2458-11-2
PMCID: PMC3091536  PMID: 21199571
18.  Cross-National Analysis of the Associations among Mental Disorders and Suicidal Behavior: Findings from the WHO World Mental Health Surveys 
PLoS Medicine  2009;6(8):e1000123.
Using data from over 100,000 individuals in 21 countries participating in the WHO World Mental Health Surveys, Matthew Nock and colleagues investigate which mental health disorders increase the odds of experiencing suicidal thoughts and actual suicide attempts, and how these relationships differ across developed and developing countries.
Background
Suicide is a leading cause of death worldwide. Mental disorders are among the strongest predictors of suicide; however, little is known about which disorders are uniquely predictive of suicidal behavior, the extent to which disorders predict suicide attempts beyond their association with suicidal thoughts, and whether these associations are similar across developed and developing countries. This study was designed to test each of these questions with a focus on nonfatal suicide attempts.
Methods and Findings
Data on the lifetime presence and age-of-onset of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) mental disorders and nonfatal suicidal behaviors were collected via structured face-to-face interviews with 108,664 respondents from 21 countries participating in the WHO World Mental Health Surveys. The results show that each lifetime disorder examined significantly predicts the subsequent first onset of suicide attempt (odds ratios [ORs] = 2.9–8.9). After controlling for comorbidity, these associations decreased substantially (ORs = 1.5–5.6) but remained significant in most cases. Overall, mental disorders were equally predictive in developed and developing countries, with a key difference being that the strongest predictors of suicide attempts in developed countries were mood disorders, whereas in developing countries impulse-control, substance use, and post-traumatic stress disorders were most predictive. Disaggregation of the associations between mental disorders and nonfatal suicide attempts showed that these associations are largely due to disorders predicting the onset of suicidal thoughts rather than predicting progression from thoughts to attempts. In the few instances where mental disorders predicted the transition from suicidal thoughts to attempts, the significant disorders are characterized by anxiety and poor impulse-control. The limitations of this study include the use of retrospective self-reports of lifetime occurrence and age-of-onset of mental disorders and suicidal behaviors, as well as the narrow focus on mental disorders as predictors of nonfatal suicidal behaviors, each of which must be addressed in future studies.
Conclusions
This study found that a wide range of mental disorders increased the odds of experiencing suicide ideation. However, after controlling for psychiatric comorbidity, only disorders characterized by anxiety and poor impulse-control predict which people with suicide ideation act on such thoughts. These findings provide a more fine-grained understanding of the associations between mental disorders and subsequent suicidal behavior than previously available and indicate that mental disorders predict suicidal behaviors similarly in both developed and developing countries. Future research is needed to delineate the mechanisms through which people come to think about suicide and subsequently progress from ideation to attempts.
Please see later in the article for Editors' Summary
Editors' Summary
Background
Suicide is a leading cause of death worldwide. Every 40 seconds, someone somewhere commits suicide. Over a year, this adds up to about 1 million self-inflicted deaths. In the USA, for example, where suicide is the 11th leading cause of death, more than 30,000 people commit suicide every year. The figures for nonfatal suicidal behavior (suicidal thoughts or ideation, suicide planning, and suicide attempts) are even more shocking. Globally, suicide attempts, for example, are estimated to be 20 times as frequent as completed suicides. Risk factors for nonfatal suicidal behaviors and for suicide include depression and other mental disorders, alcohol or drug abuse, stressful life events, a family history of suicide, and having a friend or relative commit suicide. Importantly, nonfatal suicidal behaviors are powerful predictors of subsequent suicide deaths so individuals who talk about killing themselves must always be taken seriously and given as much help as possible by friends, relatives, and mental-health professionals.
Why Was This Study Done?
Experts believe that it might be possible to find ways to decrease suicide rates by answering three questions. First, which individual mental disorders are predictive of nonfatal suicidal behaviors? Although previous studies have reported that virtually all mental disorders are associated with an increased risk of suicidal behaviors, people often have two or more mental disorders (“comorbidity”), so many of these associations may reflect the effects of only a few disorders. Second, do some mental disorders predict suicidal ideation whereas others predict who will act on these thoughts? Finally, are the associations between mental disorders and suicidal behavior similar in developed countries (where most studies have been done) and in developing countries? By answering these questions, it should be possible to improve the screening, clinical risk assessment, and treatment of suicide around the world. Thus, in this study, the researchers undertake a cross-national analysis of the associations among mental disorders (as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV]) and nonfatal suicidal behaviors.
What Did the Researchers Do and Find?
The researchers collected and analyzed data on the lifetime presence and age-of-onset of mental disorders and of nonfatal suicidal behaviors in structured interviews with nearly 110,000 participants from 21 countries (part of the World Health Organization's World Mental Health Survey Initiative). The lifetime presence of each of the 16 disorders considered (mood disorders such as depression; anxiety disorders such as post-traumatic stress disorder [PTSD]; impulse-control disorders such as attention deficit/hyperactivity disorder; and substance misuse) predicted first suicide attempts in both developed and developing countries. However, the increased risk of a suicide attempt associated with each disorder varied. So, for example, in developed countries, after controlling for comorbid mental disorders, major depression increased the risk of a suicide attempt 3-fold but drug abuse/dependency increased the risk only 2-fold. Similarly, although the strongest predictors of suicide attempts in developed countries were mood disorders, in developing countries the strongest predictors were impulse-control disorders, substance misuse disorders, and PTSD. Other analyses indicate that mental disorders were generally more predictive of the onset of suicidal thoughts than of suicide plans and attempts, but that anxiety and poor impulse-control disorders were the strongest predictors of suicide attempts in both developed and developing countries.
What Do These Findings Mean?
Although this study has several limitations—for example, it relies on retrospective self-reports by study participants—its findings nevertheless provide a more detailed understanding of the associations between mental disorders and subsequent suicidal behaviors than previously available. In particular, its findings reveal that a wide range of individual mental disorders increase the chances of an individual thinking about suicide in both developed and developing countries and provide new information about the mental disorders that predict which people with suicidal ideas will act on such thoughts. However, the findings also show that only half of people who have seriously considered killing themselves have a mental disorder. Thus although future suicide prevention efforts should include a focus on screening and treating mental disorders, ways must also be found to identify the many people without mental disorders who are at risk of suicidal behaviors.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000123.
The US National Institute of Mental Health provides information about suicide in the US: statistics and prevention
The UK National Health Service provides information about suicide, including statistics about suicide in the UK and links to other resources
The World Health Organization provides global statistics about suicide and information on suicide prevention
MedlinePlus provides links to further information and advice about suicide and about mental health (in English and Spanish)
Further details about the World Mental Health Survey Initiative and about DSM-IV are available
doi:10.1371/journal.pmed.1000123
PMCID: PMC2717212  PMID: 19668361
19.  Estimates of Outcomes Up to Ten Years after Stroke: Analysis from the Prospective South London Stroke Register 
PLoS Medicine  2011;8(5):e1001033.
Charles Wolfe and colleagues collected data from the South London Stroke Register on 3,373 first strokes registered between 1995 and 2006 and showed that between 20% and 30% of survivors have poor outcomes up to 10 years after stroke.
Background
Although stroke is acknowledged as a long-term condition, population estimates of outcomes longer term are lacking. Such estimates would be useful for planning health services and developing research that might ultimately improve outcomes. This burden of disease study provides population-based estimates of outcomes with a focus on disability, cognition, and psychological outcomes up to 10 y after initial stroke event in a multi-ethnic European population.
Methods and Findings
Data were collected from the population-based South London Stroke Register, a prospective population-based register documenting all first in a lifetime strokes since 1 January 1995 in a multi-ethnic inner city population. The outcomes assessed are reported as estimates of need and included disability (Barthel Index <15), inactivity (Frenchay Activities Index <15), cognitive impairment (Abbreviated Mental Test < 8 or Mini-Mental State Exam <24), anxiety and depression (Hospital Anxiety and Depression Scale >10), and mental and physical domain scores of the Medical Outcomes Study 12-item short form (SF-12) health survey. Estimates were stratified by age, gender, and ethnicity, and age-adjusted using the standard European population. Plots of outcome estimates over time were constructed to examine temporal trends and sociodemographic differences. Between 1995 and 2006, 3,373 first-ever strokes were registered: 20%–30% of survivors had a poor outcome over 10 y of follow-up. The highest rate of disability was observed 7 d after stroke and remained at around 110 per 1,000 stroke survivors from 3 mo to 10 y. Rates of inactivity and cognitive impairment both declined up to 1 y (280/1,000 and 180/1,000 survivors, respectively); thereafter rates of inactivity remained stable till year eight, then increased, whereas rates of cognitive impairment fluctuated till year eight, then increased. Anxiety and depression showed some fluctuation over time, with a rate of 350 and 310 per 1,000 stroke survivors, respectively. SF-12 scores showed little variation from 3 mo to 10 y after stroke. Inactivity was higher in males at all time points, and in white compared to black stroke survivors, although black survivors reported better outcomes in the SF-12 physical domain. No other major differences were observed by gender or ethnicity. Increased age was associated with higher rates of disability, inactivity, and cognitive impairment.
Conclusions
Between 20% and 30% of stroke survivors have a poor range of outcomes up to 10 y after stroke. Such epidemiological data demonstrate the sociodemographic groups that are most affected longer term and should be used to develop longer term management strategies that reduce the significant poor outcomes of this group, for whom effective interventions are currently elusive.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, 15 million people have a stroke. About 5 million of these people die within a few days, and another 5 million are left disabled. Stroke occurs when the brain's blood supply is suddenly interrupted by a blood clot blocking a blood vessel in the brain (ischemic stroke, the commonest type of stroke) or by a blood vessel in the brain bursting (hemorrhagic stroke). Deprived of the oxygen normally carried to them by the blood, the brain cells near the blockage die. The symptoms of stroke depend on which part of the brain is damaged but include sudden weakness or paralysis along one side of the body, vision loss in one or both eyes, and confusion or trouble speaking or understanding speech. Anyone experiencing these symptoms should seek immediate medical attention because prompt treatment can limit the damage to the brain. Risk factors for stroke include age (three-quarters of strokes occur in people over 65 years old), high blood pressure, and heart disease.
Why Was This Study Done?
Post-stroke rehabilitation can help individuals overcome the physical disabilities caused by stroke, and drugs and behavioral counseling can reduce the risk of a second stroke. However, people can also have problems with cognition (thinking, awareness, attention, learning, judgment, and memory) after a stroke, and they can become depressed or anxious. These “outcomes” can persist for many years, but although stroke is acknowledged as a long-term condition, most existing data on stroke outcomes are limited to a year after the stroke and often focus on disability alone. Longer term, more extensive information is needed to help plan services and to help develop research to improve outcomes. In this burden of disease analysis, the researchers use follow-up data collected by the prospective South London Stroke Register (SLSR) to provide long-term population-based estimates of disability, cognition, and psychological outcomes after a first stroke. The SLSR has recorded and followed all patients of all ages in an inner area of South London after their first-ever stroke since 1995.
What Did the Researchers Do and Find?
Between 1995 and 2006, the SLSR recorded 3,373 first-ever strokes. Patients were examined within 48 hours of referral to SLSR, their stroke diagnosis was verified, and their sociodemographic characteristics (including age, gender, and ethnic origin) were recorded. Study nurses and fieldworkers then assessed the patients at three months and annually after the stroke for disability (using the Barthel Index, which measures the ability to, for example, eat unaided), inactivity (using the Frenchay Activities Index, which measures participation in social activities), and cognitive impairment (using the Abbreviated Mental Test or the Mini-Mental State Exam). Anxiety and depression and the patients' perceptions of their mental and physical capabilities were also assessed. Using preset cut-offs for each outcome, 20%–30% of stroke survivors had a poor outcome over ten years of follow-up. So, for example, 110 individuals per 1,000 population were judged disabled from three months to ten years, rates of inactivity remained constant from year one to year eight, at 280 affected individuals per 1,000 survivors, and rates of anxiety and depression fluctuated over time but affected about a third of the population. Notably, levels of inactivity were higher among men than women at all time points and were higher in white than in black stroke survivors. Finally, increased age was associated with higher rates of disability, inactivity, and cognitive impairment.
What Do These Findings Mean?
Although the accuracy of these findings may be affected by the loss of some patients to follow-up, these population-based estimates of outcome measures for survivors of a first-ever stroke for up to ten years after the event provide concrete evidence that stroke is a lifelong condition with ongoing poor outcomes. They also identify the sociodemographic groups of patients that are most affected in the longer term. Importantly, most of the measured outcomes remain relatively constant (and worse than outcomes in an age-matched non-stroke-affected population) after 3–12 months, a result that needs to be considered when planning services for stroke survivors. In other words, these findings highlight the need for health and social services to provide long-term, ongoing assessment and rehabilitation for patients for many years after a stroke.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001033.
The US National Institute of Neurological Disorders and Stroke provides information about all aspects of stroke (in English and Spanish); the US National Institute of Health SeniorHealth Web site has additional information about stroke
The Internet Stroke Center provides detailed information about stroke for patients, families, and health professionals (in English and Spanish)
The UK National Health Service Choices Web site also provides information about stroke for patients and their families
MedlinePlus has links to additional resources about stroke (in English and Spanish)
More information about the South London Stroke Register is available
doi:10.1371/journal.pmed.1001033
PMCID: PMC3096613  PMID: 21610863
20.  Youth Anxiety and Parent Factors Over Time: Directionality of Change Among Youth Treated for Anxiety 
Objective
The relationship between improvements in child anxiety and changes in parent factors (e.g., parental anxiety, parenting behaviors) is poorly understood. The present study investigated the directionality of change for child anxiety and parent factors among youth treated for anxiety disorders.
Method
Structural equation modeling examined these relationships pre- to post-treatment and at 1-year follow-up for 111 youth aged 7–14 (57% male, 84% Caucasian). Child anxiety was measured using the Anxiety Disorders Interview Schedule for Children and the Child Behavior Checklist. The State-Trait Anxiety Inventory, Children’s Report of Parental Behavior Inventory, and Family Assessment Device were used to measure maternal anxiety, psychological control, behavior control, and family affective involvement.
Results
Findings suggest that decreases in mother-reported child anxiety led to decreases in maternal anxiety. Decreases in maternal psychological control and family affective involvement preceded decreases in clinician-rated child anxiety. Youth who showed the most reductions in anxiety over the course of treatment were those who tended to have lower family affective involvement, behavior control, and maternal anxiety at pretreatment. Stability of the parent factors and child anxiety over time suggest that stability was greater for behavior control and maternal anxiety relative to affective involvement and psychological control.
Conclusions
The findings are consistent with previous research indicating the importance of these parent factors as they relate to anxiety in youth. Furthermore, results indicate that changes in child anxiety may precede changes in parent factors and suggest that psychological control and affective involvement are important treatment targets for youth with anxiety disorders.
doi:10.1080/15374416.2012.719459
PMCID: PMC3534950  PMID: 23009743
anxiety disorders; children; parenting; cognitive-behavioral therapy; direction of change
21.  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
22.  The Invisible Suffering: Sexual Coercion, Interpersonal Violence, and Mental Health - A Cross-Sectional Study among University Students in South-Western Uganda 
PLoS ONE  2012;7(12):e51424.
Background
Despite a history of conflicts and widespread human rights violation in sub-Saharan Africa, little is known about the prevalence of interpersonal violence among the population in this region. Evidence from high-income countries suggests that exposure to violence has mental health consequences and violence also has associations with experiences of sexual coercion.
Aims
This study sought to investigate the prevalence of physical and perceived threats of violence among university students in Uganda and to assess the possible relationship between such violence, sexual coercion, and symptoms of anxiety, depression, and psychoticism, respectively.
Method
In 2005, 980 Ugandan university students responded to a self-administered questionnaire (response rate 80%) that assessed socio-demographic factors, social capital, importance of religion, mental health, experience of violence and sexual coercion, and sexual behaviour factors. Logistic regression analysis was applied as the main analytical tool.
Results
Of those who responded, 28% reported perceived threats/threats of violence and 10% exposure to actual physical violence over the previous 12 months, with no significant gender differences in exposure history. Exposure to violence was significantly associated with the experience of sexual coercion among both males and females. Sexual coercion and threats/threats of violence were both significantly associated with poor mental health in males and females, but only males showed a strong association between exposure to physical violence and poor mental health.
Conclusion
The current study suggests that in terms of general exposure, both males and females in the study population are equally exposed to sexual coercion and interpersonal violence, and both male and female students show generally similar mental health effects of exposure to such violence. The prevalence of interpersonal violence found in our study population may have long-term negative health implications. Our findings may serve as a baseline for interventions and continuing research aimed at preventing interpersonal violence.
doi:10.1371/journal.pone.0051424
PMCID: PMC3519892  PMID: 23240021
23.  Violations of the international code of marketing of breast milk substitutes: prevalence in four countries 
BMJ : British Medical Journal  1998;316(7138):1117-1122.
Objective: To estimate the prevalence of violations of the international code of marketing of substitutes for breast milk in one city in each of Bangladesh, Poland, South Africa, and Thailand.
Design: Multistage random sampling was used to select pregnant women and mothers of infants ⩽6 months old to interview at health facilities. Women were asked whether they had received free samples of substitutes for breast milk (including infant formula designed to meet the nutritional needs of infants from birth to 4 to 6 months of age, follow on formula designed to replace infant formula at the age of 4 to 6 months, and complementary foods for infants aged ⩽6 months), bottles, or teats. The source of the free sample and when it had been given to the women was also determined. 3 health workers were interviewed at each facility to assess whether the facility had received free samples, to determine how they had been used, and to determine whether gifts had been given to health workers by companies that manufactured or distributed breast milk substitutes. Compliance with the marketing code for information given to health workers was evaluated using a checklist.
Setting: Health facilities in Dhaka, Bangladesh; Warsaw, Poland; Durban, South Africa; and Bangkok, Thailand.
Subjects: 1468 pregnant women, 1582 mothers of infants aged ⩽6 months, and 466 health workers at 165 health facilities.
Main outcome measures: Number of free samples received by pregnant women, mothers, and health workers; number of gifts given to health workers; and availability of information that violated the code in health facilities.
Results: 97 out of 370 (26%) mothers in Bangkok reported receiving free samples of breast milk substitutes, infant formula, bottles, or teats compared with only 1 out of 385 mothers in Dhaka. Across the four cities from 3 out of 40 (8%) to 20 out of 40 (50%) health facilities had received free samples which were not being used for research or professional evaluation; from 2 out of 123 (2%) to 21 out of 119 (18%) health workers had received gifts from companies involved in the manufacturing or distribution of breast milk substitutes. From 6 out of 40 (15%) to 22 out of 39 (56%) health facilities information that violated the code had been provided by companies and was available to staff.
Conclusion: Violations of the code were detected with a simple survey instrument in all of the four countries studied. Governmental and non-governmental agencies should monitor the prevalence of code violations using the simple methodology developed for this study.
Key messages A simple multistage random sampling procedure can be used to interview women and health professionals to assess whether violations of the international code of marketing of substitutes for breast milk are occurring 3050 women and 466 health professionals were interviewed at 165 health facilities in Bangladesh, Poland, South Africa, and Thailand 97 out of 370 mothers in Bangkok reported receiving free samples of breast milk substitutes, infant formula, bottles, or teats compared with only 1 out of 385 mothers in Dhaka. In Bangkok health workers reported that 20 out of 40 health facilities had also received free samples. Most free samples were distributed by health facilities In Warsaw 56% of facilities surveyed were found to have information available for health workers that had been provided by manufacturers or distributors of breast milk substitutes in contravention of the code; 18% of health workers in Warsaw had received free gifts from manufacturers
PMCID: PMC28512  PMID: 9552947
24.  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
25.  Evaluation of Perceived Threat Differences Posed by Filovirus Variants 
In the United States, filoviruses (ebolaviruses and marburgviruses) are listed as National Institute of Allergy and Infectious Diseases (NIAID) Category A Priority Pathogens, Select Agents, and Centers for Disease Control and Prevention (CDC) Category A Bioterrorism Agents. In recent months, U.S. biodefense professionals and policy experts have initiated discussions on how to optimize filovirus research in regard to medical countermeasure (ie, diagnostics, antiviral, and vaccine) development. Standardized procedures and reagents could accelerate the independent verification of research results across government agencies and establish baselines for the development of animal models acceptable to regulatory entities, such as the Food and Drug Administration (FDA), while being fiscally responsible. At the root of standardization lies the question of which filovirus strains, variants, or isolates ought to be the prototypes for product development, evaluation, and validation. Here we discuss a rationale for their selection. We conclude that, based on currently available data, filovirus biodefense research ought to focus on the classical taxonomic filovirus prototypes: Marburg virus Musoke in the case of marburgviruses and Ebola virus Mayinga in the case of Zaire ebolaviruses. Arguments have been made in various committees in favor of other variants, such as Marburg virus Angola, Ci67 or Popp, or Ebola virus Kikwit, but these rationales seem to be largely based on anecdotal or unpublished and unverified data, or they may reflect a lack of awareness of important facts about the variants' isolation history and genomic properties.
Standardized procedures and reagents could accelerate the independent verification of research results across government agencies and establish baselines for the development of animal models acceptable to regulatory entities. At the root of standardization lies the question of which filovirus strains, variants, or isolates ought to be the prototypes for product development, evaluation, and validation. The authors discuss a rationale for selection and conclude that filovirus biodefense research ought to focus on the classical taxonomic filovirus prototypes.
doi:10.1089/bsp.2011.0051
PMCID: PMC3233913  PMID: 22070137

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