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BACKGROUND: In Africa, lactational amenorrhea is the major reason for birth spacing. OBJECTIVE: We studied whether the early introduction of complementary food to infants is associated with an increased risk of menstruation resumption in rural African women. DESIGN: Senegalese women (n = 855) were included at 2-3 mo postpartum and followed up at 4-5 and 6-7 mo in dispensaries. A subsample of 502 women were followed up at 9-10 mo and twice yearly at home thereafter. Risk factors for menstruation resumption were assessed with logistic regression, with control for maternal parity, occupation, education, postpartum body mass index, child sex and weight-for-age, and season. RESULTS: The risk of menstruation resumption was 4.2% (95% CI: 2.8%, 5.6%) at 6-7 mo and 6.5% (4.0%, 8.9%) at 9-10 mo. Compared with the introduction of complementary food after 6-7 mo, introduction at 2-3, 4-5, or 6-7 mo was associated with a greater odds of menstruation resumption at 6-7 mo [odds ratios (ORs): 5.08 (1.01, 25.5), 6.00 (1.29, 27.4), and 4.45 (0.96, 20.6; NS), respectively]. Introduction of food at 4-5 or 6-7 mo compared with that after 6-7 mo was associated with significantly greater odds of menstruation resumption at 6-7 mo (5.13; 1.16, 22.6) but not at 9-10 mo (3.07; 0.65, 14.4; NS) or year 2. CONCLUSION: Child age at introduction of complementary food was significantly associated with the odds of menstruation resumption at 6-7 mo postpartum. Copyright © 2003 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Introduction: This study aims to test a measure of loneliness and to document its determinants among rural men and women in Senegal., Methods: Data from the Niakhar Social Networks and Health Project were used. The analysis sample was composed of 1261 residents aged 16 years and older. Analyses were stratified by gender. Associations between loneliness and its determinants (socio-demographic characteristics and level of social integration) were examined with multivariate logistic regressions., Results: Loneliness affects almost one in three people. Its prevalence is more significant for women. Multivariate analyses indicate that for both men and women, older age intensifies loneliness and recent migration experience protects against loneliness. Other factors act differently according to gender. Widowhood or divorce for men, and residential isolation for women, worsen the experience of loneliness. Social integration protects men against loneliness, but this relationship is not found for women. Finally, the effect of the level of social integration on loneliness varies with age., Conclusions: This study, which documents a phenomenon which is often neglected by misconceptions about social solidarities in these societies, suggests that loneliness is not linked to the same issues for men and women. For men, being socially integrated and being in a union are protective, whereas for women, poor social integration does not appear to be a clear source of loneliness, unlike residential isolation.

The lagging fertility transition in West Africa has important repercussions for global population growth but remains poorly understood. Inspired by Caldwell and colleagues' fertility transition framework, as well as by subsequent research, we examine diversity in women's holistic childbearing trajectories in Niakhar, Senegal, between the early 1960s and 2018 using a sequence analysis approach. We evaluate the prevalence of different trajectories, their contribution to overall fertility levels, and their association with women's socioeconomic and cultural characteristics. Four trajectories were observed: "high fertility," "delayed entry," "truncated," and "short." While the high fertility trajectory was most prevalent across cohorts, delayed entry grew in importance. The high fertility trajectory was more common among women born between 1960 and 1969 and was followed less often by divorced women and those from polygynous households. Women with primary education and those from higher status groups were more likely to experience delayed entry. The truncated trajectory was associated with lack of economic wealth, polygynous households, and caste membership. A short trajectory was related to lack of agropastoral wealth, divorce, and possibly secondary sterility. Our study advances knowledge on fertility transitions in Niakhar-and Sahelian West African contexts more generally-by showing the diversity of childbearing trajectories within high fertility regional contexts., (Copyright © 2023 The Authors.)

Cell motility is critical for tumor malignancy. Metabolism being an obligatory step in shaping cell behavior, we looked for metabolic weaknesses shared by motile cells across the diverse genetic contexts of patients' glioblastoma. Computational analyses of single-cell transcriptomes from thirty patients' tumors isolated cells with high motile potential and highlighted their metabolic specificities. These cells were characterized by enhanced mitochondrial load and oxidative stress coupled with mobilization of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase (MPST). Functional assays with patients' tumor-derived cells and -tissue organoids, and genetic and pharmacological manipulations confirmed that the cells depend on enhanced ROS production and MPST activity for their motility. MPST action involved protection of protein cysteine residues from damaging hyperoxidation. Its knockdown translated in reduced tumor burden, and a robust increase in mice survival. Starting from cell-by-cell analyses of the patients' tumors, our work unravels metabolic dependencies of cell malignancy maintained across heterogeneous genomic landscapes., (© 2022. The Author(s).)

Social networks' influence on migration has long been explored largely through the lenses of cumulative causation and social capital theory. This article aims to reconceptualize elements of these theories for the case of rural-urban migration and test their utility in explaining first-migration timing. We use a uniquely extensive social network survey linked to prospectively collected migration data in rural Senegal. We decompose migrant networks into return migrants, current migrants, and nonmigrant residents of the destination to capture heterogeneity in migration-relevant social capital. As expected, the number of nonmigrant alters living in the capital, Dakar, has an outsized association with the migration hazard, the number of current migrants from the village living in Dakar has a smaller association, and the number of return migrants has little association. Drawing on social capital theory, we test the influence of (1) subjectively assessed tie strength between the ego and their network alters and (2) structurally weak ties measured through second-order ("friend of a friend") connections. Weak and strong subjective ties to current migrants and nonmigrant Dakar residents are positively associated with the first-migration hazard. Structurally weak ties to current migrants are too, but only for individuals with no direct ties to current migrants., (Copyright © 2022 The Authors.)

Sibling survival histories are a major source of adult mortality estimates in countries with incomplete death registration. We evaluate age and date reporting errors in sibling histories collected during a validation study in the Niakhar Health and Demographic Surveillance System (Senegal). Participants were randomly assigned to either the Demographic and Health Survey questionnaire or a questionnaire incorporating an event history calendar, recall cues, and increased probing strategies. We linked 60-62 per cent of survey reports of siblings to the reference database using manual and probabilistic approaches. Both questionnaires showed high sensitivity (>96 per cent) and specificity (>97 per cent) in recording siblings' vital status. Respondents underestimated the age of living siblings, and age at and time since death of deceased siblings. These reporting errors introduced downward biases in mortality estimates. The revised questionnaire improved reporting of age of living siblings but not of age at or timing of deaths.

Intimate partner violence (IPV) is a pressing international public health and human rights concern. Recent scholarship concerning causes of IPV has focused on the potentially critical influence of social learning and influence in interpersonal interaction through social norms. Using sociocentric network data from all individuals aged 16 years and above in a rural Senegalese village surveyed as part of the Niakhar Social Networks and Health Project ( n = 1,274), we estimate a series of nested linear probability models to test the association between characteristics of respondents' social networks and residential compounds (including educational attainment, health ideation, socioeconomic status, and religion) and whether respondents are classified as finding IPV acceptable, controlling for individual characteristics. We also test for direct social learning effects, estimating the association between IPV acceptability among network members and co-residents and respondents' own, net of these factors. We find individual, social network, and residential compound factors are all associated with IPV acceptability. On the individual level, these include gender, traditional health ideation, and household agricultural investment. Residential compound-level associations are largely explained in the presence of the individual and network characteristics, except for that concerning educational attainment. We find that network alters' IPV acceptability is strongly positively associated with respondents' own, net of individual and compound-level characteristics. A 10% point higher probability of IPV acceptability in respondents' networks is estimated to be associated with a 4.5% point higher likelihood of respondents being classified as finding IPV acceptable. This research provides compelling evidence that social interaction through networks exerts an important, potentially normative, influence on whether individuals in this population perceive IPV as acceptable or not. It also suggests that interventions targeting individuals most likely to perceive IPV as acceptable may have a multiplier effect, influencing the normative context of others they interact with through their social networks.

Background: Research concerning the causes and consequences of intimate partner violence (IPV), particularly in less developed areas of the world, has become prominent in the last two decades. Although a number of potential causal factors have been investigated the current consensus is that attitudes toward IPV on the individual level, likely representing perceptions of normative behavior, and the normative acceptability of IPV on the aggregate level likely play key roles. Measurement of both is generally approached through either binary indicators of acceptability of any type of IPV or additive composite indexes of multiple indicators. Both strategies imply untested assumptions which potentially have important implications for both research into the causes and consequences of IPV as well as interventions aimed to reduce its prevalence., Methods: Using survey data from rural Senegal collected in 2014, this analysis estimates latent class measurement models of attitudes concerning the acceptability of IPV. We investigate the dimensional structure of IPV ideation and test the parallel indicator assumption implicit in common measurement strategies, as well as structural and measurement invariance between men and women., Results: We find that a two-class model of the acceptability of IPV in which the conditional probability of class membership is allowed to vary between the sexes is preferred for both men and women. Though the assumption of structural invariance between men and women is supported, measurement invariance and the assumption of parallel indicators (or equivalence of indicators used) are not., Conclusions: Measurement strategies conventionally used to operationalize the acceptability of IPV, key to modeling perceptions of norms around IPV, are a poor fit to the data used here. Research concerning the measurement characteristics of IPV acceptability is a precondition for adequate investigation of its causes and consequences, as well as for intervention efforts aimed at reducing or eliminating IPV.

The adolescent birth rate (ABR) is an important indicator of maternal health, adolescent sexual health, and gender equity; it remains high in sub-Saharan Africa. While Demographic and Health Surveys (DHS) are the main source of ABR estimates, Health and Demographic Surveillance Systems (HDSS) also produce ABRs. Studies are lacking, however, to assess the ease of access and accuracy of HDSS ABR measures. In this paper, we use birth and exposure data from 10 HDSS in six African countries to compute local ABRs and compare these rates to DHS regional rates where the HDSS sites are located, standardizing by education and place of residence. In rural HDSS sites, the ABR measure is on average 44 percent lower than the DHS measure, after controlling for education and place of residence. Strong temporary migration of childless young women out of rural areas and different capacities in capturing temporarily absent women in the DHS and HDSS could explain this discrepancy. Further comparisons based on more strictly similar populations and measures seem warranted., (© 2020 The Population Council, Inc.)

Glioblastoma cell ability to adapt their functioning to microenvironment changes is a source of the extensive intra-tumor heterogeneity characteristic of this devastating malignant brain tumor. A systemic view of the metabolic pathways underlying glioblastoma cell functioning states is lacking. We analyzed public single cell RNA-sequencing data from glioblastoma surgical resections, which offer the closest available view of tumor cell heterogeneity as encountered at the time of patients' diagnosis. Unsupervised analyses revealed that information dispersed throughout the cell transcript repertoires encoded the identity of each tumor and masked information related to cell functioning states. Data reduction based on an experimentally-defined signature of transcription factors overcame this hurdle. It allowed cell grouping according to their tumorigenic potential, regardless of their tumor of origin. The approach relevance was validated using independent datasets of glioblastoma cell and tissue transcriptomes, patient-derived cell lines and orthotopic xenografts. Overexpression of genes coding for amino acid and lipid metabolism enzymes involved in anti-oxidative, energetic and cell membrane processes characterized cells with high tumorigenic potential. Modeling of their expression network highlighted the very long chain polyunsaturated fatty acid synthesis pathway at the core of the network. Expression of its most downstream enzymatic component, ELOVL2, was associated with worsened patient survival, and required for cell tumorigenic properties in vivo. Our results demonstrate the power of signature-driven analyses of single cell transcriptomes to obtain an integrated view of metabolic pathways at play within the heterogeneous cell landscape of patient tumors.

This paper presents details of the design and implementation of the Niakhar Social Networks and Health Project (NSNHP), a large, mixed-methods project funded by the U.S. National Institute of General Medical Sciences (NIGMS). By redressing fundamental problems in conventional survey network data collection methods, the project is aimed at improving inferences concerning the association between social network structures and processes and health behaviors and outcomes. Fielded in collaboration with an ongoing demographic and health surveillance system in rural Senegal, the NSNHP includes qualitative data concerning the dimensions of social association and health ideologies and behaviors in the study zone, two panels of a new social network survey, and several supplementary and affiliated data sets. •Longitudinal social network survey linked to pre-existing surveillance data•Addresses fundamental methodological constraints in previous social network data•Enables social network analyses of health beliefs, behaviors, and outcomes.

The preference in many parts of the world for ethnomedical therapy over biomedical alternatives has long confounded scholars of medicine and public health. In the anthropological literature cultural and interactional contexts have been identified as fundamental mechanisms shaping adherence to ethnomedical beliefs and health seeking behaviors. In this paper, we examine the association between individual, neighborhood, and social network characteristics and the likelihood of attachment to an ethnomedical cultural model encompassing beliefs about etiology of disease, appropriate therapeutic and preventative measures, and more general beliefs about metaphysics and the efficacy of health systems in a rural population in Eastern Senegal. Using data from a unique social network survey, and supplemented by extensive qualitative research, we model attachment to the ethnomedical model at each of these levels as a function of demographic, economic and ideational characteristics, as well as perceived effectiveness of both biomedical and ethnomedical therapy. Individuals' attachment to the ethnomedical cultural model is found to be strongly associated with characteristics of their neighborhoods, and network alters. Experiences with ethnomedical care among neighbors, and both ethnomedical and biomedical care among network alters, are independently associated with attachment to the ethnomedical model, suggesting an important mechanism for cultural change. At the same time, we identify an independent association between network alters' cultural models and those of respondents, indicative of a direct cultural learning or influence mechanism, modified by the degree of global transitivity, or 'connectedness' of individuals' networks. This evidence supports the long held theoretical position that symbolic systems concerning illness and disease are shared, reproduced, and changed through mechanisms associated with social interaction. This has potentially important implications not only for public health programming, but for the understanding of the reproduction and evolution of cultural systems more generally., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Although a growing body of evidence indicates that phenotypic plasticity exhibited by glioblastoma cells plays a central role in tumor development and post-therapy recurrence, the master drivers of their aggressiveness remain elusive. Here we mapped the changes in active (H3K4me3) and repressive (H3K27me3) histone modifications accompanying the repression of glioblastoma stem-like cells tumorigenicity. Genes with changing histone marks delineated a network of transcription factors related to cancerous behavior, stem state, and neural development, highlighting a previously unsuspected association between repression of ARNT2 and loss of cell tumorigenicity. Immunohistochemistry confirmed ARNT2 expression in cell sub-populations within proliferative zones of patients' glioblastoma. Decreased ARNT2 expression was consistently observed in non-tumorigenic glioblastoma cells, compared to tumorigenic cells. Moreover, ARNT2 expression correlated with a tumorigenic molecular signature at both the tissue level within the tumor core and at the single cell level in the patients' tumors. We found that ARNT2 knockdown decreased the expression of SOX9, POU3F2 and OLIG2, transcription factors implicated in glioblastoma cell tumorigenicity, and repressed glioblastoma stem-like cell tumorigenic properties in vivo. Our results reveal ARNT2 as a pivotal component of the glioblastoma cell tumorigenic signature, located at a node of a transcription factor network controlling glioblastoma cell aggressiveness.

Selective antagonists at serotonin 5-HT 6 receptors (5-HT 6 R) improve memory performance in rodents and are currently under clinical investigations. If blockade of 5-HT 6 R is known to increase glutamate release, only two studies have so far demonstrated an interaction between 5-HT 6 R and glutamate transmission, but both, using the non-competitive NMDA antagonist MK-801, insensitive to variations of glutamate concentrations. In a place recognition task, we investigated here in mice the role of glutamate transmission in the beneficial effects of 5-HT 6 R blockade (SB-271046). Through the use of increasing intervals (2, 4 and 6h) between acquisition and retrieval, we investigated the time-dependent impact of two different glutamatergic modulators. NMDAR-dependant glutamate transmission (NMDA Receptors) was either blocked by the competitive antagonist at NMDAR, CGS 19755, or potentiated by the glycine transporter type 1 (GlyT1) inhibitor, NFPS. Results showed that neither SB-271046, nor CGS 19755, nor NFPS, alter behavioural performances after short intervals, i.e. when control mice displayed significant memory performances (2h and 4h) (respectively 10, 3, and 0.625mg.kg -1 ). Conversely, with the 6h-interval, a situation in which spontaneous forgetting is observed in control mice, SB-271046 improved recognition memory performances. This beneficial effect was prevented when co-administered with either CGS 19755 or NFPS, which themselves had no effect. Interestingly, a dose-dependent effect was observed with NFPS, with promnesic effect observed at lower dose (0.156mg.kg -1 ) when administrated alone, whereas it did no modify promnesic effect of SB-271046. These results demonstrate that promnesiant effect induced by 5-HT 6 R blockade is sensitive to the competitive blockade of NMDAR and underline the need of a fine adjustment of the inhibition of GlyT1. Overall, our findings support the idea of a complex crosstalk between serotonergic and glutamatergic systems in the promnesic properties of 5-HT 6 R antagonists., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: In low- and middle-income countries (LMICs), siblings' survival histories (SSH) are often used to estimate maternal mortality, but SSH data on causes of death at reproductive ages have seldom been validated. We compared the accuracy of two SSH instruments: the standard questionnaire used during the demographic and health surveys (DHS) and the siblings' survival calendar (SSC), a new questionnaire designed to improve survey reports of deaths among women of reproductive ages., Methods: We recruited 1189 respondents in a SSH survey in Niakhar, Senegal. Mortality records from a health and demographic surveillance system (HDSS) constituted the reference data set. Respondents were randomly assigned to an interview with the DHS or SSC questionnaires. A total of 164 respondents had a sister who died at reproductive ages over the past 15 years before the survey according to the HDSS., Results: The DHS questionnaire led to selective omissions of deaths: DHS respondents were significantly more likely to report their sister's death if she had died of pregnancy-related causes than if she had died of other causes (96.4% vs. 70.9%, P < 0.007). Among reported deaths, both questionnaires had high sensitivity (>90%) in recording pregnancy-related deaths. But the DHS questionnaire had significantly lower specificity than the SSC (79.5% vs. 95.0%, P = 0.015). The DHS questionnaire overestimated the proportion of deaths due to pregnancy-related causes, whereas the SSC yielded unbiased estimates of this parameter., Conclusion: Statistical models informed by SSH data collected using the DHS questionnaire might exaggerate maternal mortality in Senegal and similar settings. A new questionnaire, the SSC, could permit better tracking progress towards the reduction in maternal mortality., (© 2015 John Wiley & Sons Ltd.)

Background: Women continue to die in unacceptably large numbers around the world as a result of pregnancy, particularly in sub-Saharan Africa and Asia. Part of the problem is a lack of accurate, population-based information characterising the issues and informing solutions. Population surveillance sites, such as those operated within the INDEPTH Network, have the potential to contribute to bridging the information gaps., Objective: To describe patterns of pregnancy-related mortality at INDEPTH Network Health and Demographic Surveillance System sites in sub-Saharan Africa and southeast Asia in terms of maternal mortality ratio (MMR) and cause-specific mortality rates., Design: Data on individual deaths among women of reproductive age (WRA) (15-49) resident in INDEPTH sites were collated into a standardised database using the INDEPTH 2013 population standard, the WHO 2012 verbal autopsy (VA) standard, and the InterVA model for assigning cause of death., Results: These analyses are based on reports from 14 INDEPTH sites, covering 14,198 deaths among WRA over 2,595,605 person-years observed. MMRs varied between 128 and 461 per 100,000 live births, while maternal mortality rates ranged from 0.11 to 0.74 per 1,000 person-years. Detailed rates per cause are tabulated, including analyses of direct maternal, indirect maternal, and incidental pregnancy-related deaths across the 14 sites., Conclusions: As expected, these findings confirmed unacceptably high continuing levels of maternal mortality. However, they also demonstrate the effectiveness of INDEPTH sites and of the VA methods applied to arrive at measurements of maternal mortality that are essential for planning effective solutions and monitoring programmatic impacts.

Background: As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data., Objective: To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia., Design: Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population., Results: The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates., Conclusions: Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.

Background: Mortality from non-communicable diseases (NCDs) is a major global issue, as other categories of mortality have diminished and life expectancy has increased. The World Health Organization's Member States have called for a 25% reduction in premature NCD mortality by 2025, which can only be achieved by substantial reductions in risk factors and improvements in the management of chronic conditions. A high burden of NCD mortality among much older people, who have survived other hazards, is inevitable. The INDEPTH Network collects detailed individual data within defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available., Objective: To describe patterns of adult NCD mortality from INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories, with separate consideration of premature (15-64 years) and older (65+ years) NCD mortality., Design: All adult deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates., Results: A total of 80,726 adult (over 15 years) deaths were documented over 7,423,497 person-years of observation. NCDs were attributed as the cause for 35.6% of these deaths. Slightly less than half of adult NCD deaths occurred in the 15-64 age group. Detailed results are presented by age and sex for leading causes of NCD mortality. Per-site rates of NCD mortality were significantly correlated with rates of HIV/AIDS-related mortality., Conclusions: These findings present important evidence on the distribution of NCD mortality across a wide range of African and Asian settings. This comes against a background of global concern about the burden of NCD mortality, especially among adults aged under 70, and provides an important baseline for future work.

Background: Childhood mortality, particularly in the first 5 years of life, is a major global concern and the target of Millennium Development Goal 4. Although the majority of childhood deaths occur in Africa and Asia, these are also the regions where such deaths are least likely to be registered. The INDEPTH Network works to alleviate this problem by collating detailed individual data from defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available., Objective: To present a description of cause-specific mortality rates and fractions over the first 15 years of life as documented by INDEPTH Network sites in sub-Saharan Africa and south-east Asia., Design: All childhood deaths at INDEPTH sites are routinely registered and followed up with verbal autopsy (VA) interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provided person-time denominators for mortality rates. Cause-specific mortality rates and cause-specific mortality fractions are presented according to WHO 2012 VA cause groups for neonatal, infant, 1-4 year and 5-14 year age groups., Results: A total of 28,751 childhood deaths were documented during 4,387,824 person-years over 18 sites. Infant mortality ranged from 11 to 78 per 1,000 live births, with under-5 mortality from 15 to 152 per 1,000 live births. Sites in Vietnam and Kenya accounted for the lowest and highest mortality rates reported., Conclusions: Many children continue to die from relatively preventable causes, particularly in areas with high rates of malaria and HIV/AIDS. Neonatal mortality persists at relatively high, and perhaps sometimes under-documented, rates. External causes of death are a significant childhood problem in some settings.

Background: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies., Objective: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions., Design: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality., Results: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level., Conclusions: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology.

Background: Because most deaths in Africa and Asia are not well documented, estimates of mortality are often made using scanty data. The INDEPTH Network works to alleviate this problem by collating detailed individual data from defined Health and Demographic Surveillance sites. By registering all deaths over time and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available., Objective: To build a large standardised mortality database from African and Asian sites, detailing the relevant methods, and use it to describe cause-specific mortality patterns., Design: Individual demographic and verbal autopsy (VA) data from 22 INDEPTH sites were collated into a standardised database. The INDEPTH 2013 population was used for standardisation. The WHO 2012 VA standard and the InterVA-4 model were used for assigning cause of death., Results: A total of 111,910 deaths occurring over 12,204,043 person-years (accumulated between 1992 and 2012) were registered across the 22 sites, and for 98,429 of these deaths (88.0%) verbal autopsies were successfully completed. There was considerable variation in all-cause mortality between sites, with most of the differences being accounted for by variations in infectious causes as a proportion of all deaths., Conclusions: This dataset documents individual deaths across Africa and Asia in a standardised way, and on an unprecedented scale. While INDEPTH sites are not constructed to constitute a representative sample, and VA may not be the ideal method of determining cause of death, nevertheless these findings represent detailed mortality patterns for parts of the world that are severely under-served in terms of measuring mortality. Further papers explore details of mortality patterns among children and specifically for NCDs, external causes, pregnancy-related mortality, malaria, and HIV/AIDS. Comparisons will also be made where possible with other findings on mortality in the same regions. Findings presented here and in accompanying papers support the need for continued work towards much wider implementation of universal civil registration of deaths by cause on a worldwide basis.

Background: In countries with limited vital registration, adult mortality is frequently estimated using siblings' survival histories (SSHs) collected during Demographic and Health Surveys (DHS). These data are affected by reporting errors. We developed a new SSH questionnaire, the siblings' survival calendar (SSC). It incorporates supplementary interviewing techniques to limit omissions of siblings and uses an event history calendar to improve reports of dates and ages. We hypothesized that the SSC would improve the quality of adult mortality data., Methods and Findings: We conducted a retrospective validation study among the population of the Niakhar Health and Demographic Surveillance System in Senegal. We randomly assigned men and women aged 15-59 y to an interview with either the DHS questionnaire or the SSC. We compared SSHs collected in each group to prospective data on adult mortality collected in Niakhar. The SSC reduced respondents' tendency to round reports of dates and ages to the nearest multiple of five or ten ("heaping"). The SSC also had higher sensitivity in recording adult female deaths: among respondents whose sister(s) had died at an adult age in the past 15 y, 89.6% reported an adult female death during SSC interviews versus 75.6% in DHS interviews (p = 0.027). The specificity of the SSC was similar to that of the DHS questionnaire, i.e., it did not increase the number of false reports of deaths. However, the SSC did not improve the reporting of adult deaths among the brothers of respondents. Study limitations include sample selectivity, limited external validity, and multiple testing., Conclusions: The SSC has the potential to collect more accurate SSHs than the questionnaire used in DHS. Further research is needed to assess the effects of the SSC on estimates of adult mortality rates. Additional validation studies should be conducted in different social and epidemiological settings., Trial Registration: Controlled-Trials.com ISRCTN06849961

Crude rates such as the crude death rate are functions of both the age-specific rates and the age composition of a population. However, differences in the age structure between two populations or two time periods can result in specious differences in the corresponding crude rates making direct comparisons between populations or across time inappropriate. Therefore, when comparing crude rates between populations, it is desirable to eliminate or minimize the influence of age composition. This task is accomplished by using a standard age structure yielding an age-standardized rate. This paper proposes an updated International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) standard for use in low- and middle-income countries (LMICs) based on newly available data from the health and demographic surveillance system site members of the INDEPTH network located throughout Africa and southern Asia. The updated INDEPTH standard should better reflect the age structure of LMICs and result in more accurate health indicators and demographic rates. We demonstrate use of the new INDEPTH standard along with several existing 'world' standards and show how resulting age-standardized crude deaths rates differ when using the various standard age compositions.

Background: Bariatric surgery underwent a dramatic change in the past decade in France. The objective of this study was to examine elective bariatric surgical procedures from 2005 to 2011 in France and to determine trends in the use of the procedure., Methods: Data were extracted from the National Hospital Database. All admissions involving a bariatric surgery procedure were included. Procedures authorized by the Public Health Authority for the treatment of morbid obesity, including the adjustable gastric banding (AGB), vertical banded gastroplasty (VBG), gastric bypass (GB), sleeve gastrectomy (SG), and biliopancreatic diversion (BPD), either by laparotomic or laparoscopic approach, were retrieved. Revisional procedures, such as band removal or repositioning, band changing, and access device revisions, were also evaluated., Results: We observed a 2.5-fold increase in bariatric procedures, from 12,800 in 2005 to 31,000 in 2011. Sleeve gastrectomy and gastric bypass became the most common bariatric procedures in France in 2011, whereas adjustable gastric banding has been decreasing since 2007. During the analysis period, about 50,000 revisional procedures were performed. The number of hospitals (private or public) providing bariatric surgery has considerably increased. However, most of the activity remains confined to a small number of centers, as 50% of all bariatric surgeries are carried out in 12% of hospitals. Bariatric procedures are predominantly performed in private hospitals., Conclusions: In France the number of bariatric procedures increased considerably between 2005 and 2011. The type of procedures changed, with a constant decrease of AGB and an important increase of SG and GB. Most bariatric procedures are still performed in low volume activity hospitals and in private hospitals., (© 2013 American Society for Bariatric Surgery Published by American Society for Metabolic and Bariatric Surgery All rights reserved.)

The Health and Demographic Surveillance System (HDSS) in Niakhar, a rural area of Senegal, is located 135 km east of Dakar. The HDSS was established in 1962 by the Institut de Recherche pour le Développement (IRD) of Senegal to face the shortcomings of the civil registration system and provide demographic indicators. Some 65 villages in the Niakhar area were followed annually by the HDSS from 1962-1969. The study zone was reduced to 8 villages from 1969-1983, and from then on the HDSS was extended to include 22 other villages, covering a total of 30 villages for a population estimated at 43 000 in January 2012. Thus, 8 villages in the Niakhar area have been under demographic surveillance for almost 50 years and 30 villages for 30 years. Vital events, migrations, marital changes, pregnancies, and immunizations are routinely recorded every 4 months. The HDSS data base also includes epidemiological, economic, and environmental information obtained from specific surveys. Data were collected through annual rounds from 1962 to 1987. The rounds became weekly from 1987-1997, followed by routine visits conducted every 3 months between 1997 and 2007 and every 4 months since then. The data collected in the HDSS are not open to access, but can be fairly shared under conditions of collaboration and endowment.

The engineered protein inhibitor of human neutrophil elastase, Epi-hNE4, is being developed for the treatment of cystic fibrosis. Like many recombinant proteins, Epi-hNE4 may induce antibodies in pre-clinical species and in humans. The aim of this report was to validate an ELISA to assess its immunogenicity in monkeys. We have designed and optimized a classical ELISA in which Epi-hNE4 was coated directly on microtitre plates and the antibodies were detected using a secondary antibody labelled with peroxidase. We report implementation of the recent recommendations proposed for the validation of immunogenicity assessment. The cut-off point was determined by means of statistical analysis of negative samples. Linearity, reproducibility, stability and specificity were estimated using quality control samples obtained from a pool of positive samples. The method was applied to monkeys given Epi-hNE4 by inhalation. A confirmation test and a neutralization assay were developed in order to further assess positive samples. In conclusion, we present here one of the first examples of validation in application of recent recommendations [A.R. Mire-Sluis, Y.C. Barrett, V. Devanarayan, E. Koren, H. Liu, M. Maia, T. Parish, G. Scott, G. Shankar, E. Shores, S.J. Swanson, G. Taniguchi, D. Wierda, L.A. Zuckerman, J. Immunol. Methods 289 (2004) 1-16].

Background: In African rural settings, medically certified information on causes of death is largely lacking. The authors applied the verbal autopsy to identify causes of death before 15 years old in a rural area of Senegal where a demographic surveillance system is operating., Methods: Between 1989 and 2000, a postmortem interview was conducted using a standardized questionnaire which was independently reviewed by two physicians who assigned the probable underlying cause of death. Discordant diagnoses were discussed by a panel of physicians. Causes of death were grouped into a few categories; cause-specific mortality rates and fractions were generated., Results: Between 1989 and 1997, all-cause mortality fluctuated. Diarrhoeal diseases, malaria and acute respiratory infections explained between 30% and 70% of the mortality before 10 years of age. In children 1-9 years old, malaria death rate increased between 1989 and 1994 and thereafter did not change. The 1998-2000 years were marked by a peak in mortality, attributed to a meningitis outbreak in children more than one year old paralleled by an increase in death rate from fever of unknown origin, diarrhoeal diseases, and acute respiratory infections in children under 5 years., Conclusions: Verbal autopsy provided useful information on the mortality structure responsible for the 1998-2000 peak in mortality. It underlined that, outside outbreak situations, malaria was a leading cause of death for 1-9 year old children and that diarrhoea, acute respiratory infections, or fever from unknown origin accounted for up to 50% of the deaths among the children under 5 years.