Community interventions to reduce child mortality in Dhanusha, Nepal: study protocol for a cluster randomized controlled trial

Background: Neonatal mortality remains high in rural Nepal. Previous work suggests that local women's groups can effect significant improvement through community mobilisation. The possibility of identification and management of newborn infections by community-based workers has also arisen.Methods/Design: The objective of this trial is to evaluate the effects on newborn health of two community-based interventions involving Female Community Health Volunteers.MIRA Dhanusha community groups: a participatory intervention with women's groups. MIRA Dhanusha sepsis management: training of community volunteers in the recognition and management of neonatal sepsis. The study design is a cluster randomized controlled trial involving 60 village development committee clusters allocated 1:1 to two interventions in a factorial design.MIRA Dhanusha community groups: Female Community Health Volunteers (FCHVs) are supported in convening monthly women's groups. Nine groups per cluster (270 in total) work through two action research cycles in which they (i) identify local issues around maternity, newborn health and nutrition, (ii) prioritise key problems, (iii) develop strategies to address them, (iv) implement the strategies, and (v) evaluate their success. Cycle 1 focuses on maternal and newborn health and cycle 2 on nutrition in pregnancy and infancy and associated postpartum care practices. MIRA Dhanusha sepsis management: FCHVs are trained to care for vulnerable newborn infants. They (i) identify local births, (ii) identify low birth weight infants, (iii) identify possible newborn infection, (iv) manage the process of treatment with oral antibiotics and referral to a health facility to receive parenteral gentamicin, and (v) follow up infants and support families.Primary outcome: neonatal mortality rates. Secondary outcomes: MIRA Dhanusha community group: stillbirth, infant and under-two mortality rates, care practices and health care seeking behaviour, maternal diet, breastfeeding and complementary feeding practices, maternal and under-2 anthropometric status. MIRA Dhanusha sepsis management: identification and treatment of neonatal sepsis by community health volunteers, infection-specific neonatal mortality

Effectiveness of female community health volunteers in the detection and management of low-birth-weight in Nepal

Introduction: Low birth weight (LBW) is a major risk factor for neonatal death. However, most neonates in low-income countries are not weighed at birth. This results in many LBW infants being overlooked. Female community health volunteers (FCHVs) in Nepal are non-health professionals who are living in local communities and have already worked in a field of reproductive and child health under the government of Nepal for more than 20 years. The effectiveness of involving FCHVs to detect LBW infants and to initiate prompt action for their care was studied in rural areas of Nepal. Methods: FCHVs were tasked with weighing all neonates born in selected areas using color-coded spring scales. Supervisors repeated each weighing using electronic scales as the gold standard comparator. Data on the relative birth sizes of the infants, as assessed by their mothers, were also collected and compared with the measured weights. Each of the 205 FCHVs involved in the study was asked about the steps that she would take when she came across a LBW infant, and knowledge of zeroing a spring scale was also assessed through individual interviews. The effect of the background social characteristics of the FCHVs on their performance was examined by logistic regression. This study was nested within a community-based neonatal sepsis-management intervention surveillance system, which facilitated an assessment of the performance of the FCHVs in weighing neonates, coverage of FCHVs’ visits, and weighing of babies through maternal interviews. Results: A total of 462 babies were weighed, using both spring scales and electronic scales, within 72 hours of birth. The prevalence of LBW, as assessed by the gold standard method, was 28%. The sensitivity of detection of LBW by FCHVs was 89%, whereas the sensitivity of the mothers’ perception of size at birth was only 40%. Of the 205 FCHVs participating in the study, 70% of FCHVs understood what they should do when they identified LBW and very low birth weight (VLBW) infants. Ninety-six per cent could describe how to zero a scale and approximately 50% could do it correctly. Seventy-seven per cent of FCHVs weighed infants at least once during the study period, and 19 of them (12%) miscategorized infant weights. Differences were not detected between the background social characteristics of FCHVs who miscategorized infants and those who did not. On the basis of maternal reporting, 67% of FCHVs who visited infants had weighed them. Conclusions: FCHVs are able to correctly identify LBW and VLBW infants using spring scales and describe the correct steps to take after identification of these infants. Use of FCHVs as newborn care providers allows for utilization of their logistical, geographical, and cultural strengths, particularly a high level of access to neonates, that can complement the Nepalese healthcare system. Providing additional training to and increasing supervision of local FCHVs regarding birth weight measurement will increase the identification of high-risk neonates in resource-limited settings

Smartphone tool to collect repeated 24 h dietary recall data in Nepal

Objective To outline the development of a smartphone-based tool to collect thrice-repeated 24 h dietary recall data in rural Nepal, and to describe energy intakes, common errors and researchers' experiences using the tool. Design We designed a novel tool to collect multi-pass 24 h dietary recalls in rural Nepal by combining the use of a CommCare questionnaire on smartphones, a paper form, a QR (quick response)-coded list of foods and a photographic atlas of portion sizes. Twenty interviewers collected dietary data on three non-consecutive days per respondent, with three respondents per household. Intakes were converted into nutrients using databases on nutritional composition of foods, recipes and portion sizes. Setting Dhanusha and Mahottari districts, Nepal. Subjects Pregnant women, their mothers-in-law and male household heads. Energy intakes assessed in 150 households; data corrections and our experiences reported from 805 households and 6765 individual recalls. Results Dietary intake estimates gave plausible values, with male household heads appearing to have higher energy intakes (median (25th-75th centile): 12 079 (9293-14 108) kJ/d) than female members (8979 (7234-11 042) kJ/d for pregnant women). Manual editing of data was required when interviewers mistook portions for food codes and for coding items not on the food list. Smartphones enabled quick monitoring of data and interviewer performance, but we initially faced technical challenges with CommCare forms crashing. Conclusions With sufficient time dedicated to development and pre-testing, this novel smartphone-based tool provides a useful method to collect data. Future work is needed to further validate this tool and adapt it for other contexts

Participatory Women's Groups with Cash Transfers Can Increase Dietary Diversity and Micronutrient Adequacy during Pregnancy, whereas Women's Groups with Food Transfers Can Increase Equity in Intrahousehold Energy Allocation

Background: There is scarce evidence on the impacts of food transfers, cash transfers, or women's groups on food sharing, dietary intakes, or nutrition during pregnancy, when nutritional needs are elevated. // Objective: This study measured the effects of 3 pregnancy-focused nutrition interventions on intrahousehold food allocation, dietary adequacy, and maternal nutritional status in Nepal. // Methods: Interventions tested in a cluster-randomized controlled trial (ISRCTN 75964374) were “Participatory Learning and Action” (PLA) monthly women's groups, PLA with transfers of 10 kg fortified flour (“Super Cereal”), and PLA plus transfers of 750 Nepalese rupees (∼US$7.5) to pregnant women. Control clusters received usual government services. Primary outcomes were Relative Dietary Energy Adequacy Ratios (RDEARs) between pregnant women and male household heads and pregnant women and their mothers-in-law. Diets were measured by repeated 24-h dietary recalls. // Results: Relative to control, RDEARs between pregnant women and their mothers-in-law were 12% higher in the PLA plus food arm (log-RDEAR coefficient = 0.12; 95% CI: 0.02, 0.21; P = 0.014), but 10% lower in the PLA-only arm between pregnant women and male household heads (−0.11; 95% CI: −0.19, −0.02; P = 0.020). In all interventions, pregnant women's energy intakes did not improve, but odds of pregnant women consuming iron-folate supplements were 2.5–4.6 times higher, odds of pregnant women consuming more animal-source foods than the household head were 1.7–2.4 times higher, and midupper arm circumference was higher relative to control. Dietary diversity was 0.4 food groups higher in the PLA plus cash arm than in the control arm. // Conclusions: All interventions improved maternal diets and nutritional status in pregnancy. PLA women's groups with food transfers increased equity in energy allocation, whereas PLA with cash improved dietary diversity. PLA alone improved diets, but effects were mixed. Scale-up of these interventions in marginalized populations is a policy option, but researchers should find ways to increase adherence to interventions. This trial was registered at www.controlled-trials.com as ISRCTN 75964374

TL1A Selectively Enhances IL-12/IL-18-Induced NK Cell Cytotoxicity against NK-Resistant Tumor Targets

# The Author(s) 2010. This article is published with open access at Springerlink.com Introduction TL1A (TNFSF15) augments IFN-γ production by IL-12/IL-18 responsive human T cells. Its ligand, death domain receptor 3 (DR3), is induced by activation on T and NK cells. Although IL-12/IL-18 induces DR3 expression on most NK cells, addition of TL1A minimally increases IFN-

Quantifying the Spatial Ecology of Wide-Ranging Marine Species in the Gulf of California: Implications for Marine Conservation Planning

There is growing interest in systematic establishment of marine protected area (MPA) networks and representative conservation sites. This movement toward networks of no-take zones requires that reserves are deliberately and adequately spaced for connectivity. Here, we test the network functionality of an ecoregional assessment configuration of marine conservation areas by evaluating the habitat protection and connectivity offered to wide-ranging fauna in the Gulf of California (GOC, Mexico). We first use expert opinion to identify representative species of wide-ranging fauna of the GOC. These include leopard grouper, hammerhead sharks, California brown pelicans and green sea turtles. Analyzing habitat models with both structural and functional connectivity indexes, our results indicate that the configuration includes large proportions of biologically important habitat for the four species considered (25–40%), particularly, the best quality habitats (46–57%). Our results also show that connectivity levels offered by the conservation area design for these four species may be similar to connectivity levels offered by the entire Gulf of California, thus indicating that connectivity offered by the areas may resemble natural connectivity. The selected focal species comprise different life histories among marine or marine-related vertebrates and are associated with those habitats holding the most biodiversity values (i.e. coastal habitats); our results thus suggest that the proposed configuration may function as a network for connectivity and may adequately represent the marine megafauna in the GOC, including the potential connectivity among habitat patches. This work highlights the range of approaches that can be used to quantify habitat protection and connectivity for wide-ranging marine species in marine reserve networks

Differential Effects of Antibiotic Therapy on the Structure and Function of Human Gut Microbiota

The human intestinal microbiota performs many essential functions for the host. Antimicrobial agents, such as antibiotics (AB), are also known to disturb microbial community equilibrium, thereby having an impact on human physiology. While an increasing number of studies investigate the effects of AB usage on changes in human gut microbiota biodiversity, its functional effects are still poorly understood. We performed a follow-up study to explore the effect of ABs with different modes of action on human gut microbiota composition and function. Four individuals were treated with different antibiotics and samples were taken before, during and after the AB course for all of them. Changes in the total and in the active (growing) microbiota as well as the functional changes were addressed by 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. We have found that the class of antibiotic, particularly its antimicrobial effect and mode of action, played an important role in modulating the gut microbiota composition and function. Furthermore, analysis of the resistome suggested that oscillatory dynamics are not only due to antibiotic-target resistance, but also to fluctuations in the surviving bacterial community. Our results indicated that the effect of AB on the human gut microbiota relates to the interaction of several factors, principally the properties of the antimicrobial agent, and the structure, functions and resistance genes of the microbial community

Genome-Wide Maps of Circulating miRNA Biomarkers for Ulcerative Colitis

Inflammatory Bowel Disease – comprised of Crohn's Disease and Ulcerative Colitis (UC) - is a complex, multi-factorial inflammatory disorder of the gastrointestinal tract. In this study we have explored the utility of naturally occurring circulating miRNAs as potential blood-based biomarkers for non-invasive prediction of UC incidences. Whole genome maps of circulating miRNAs in micro-vesicles, Peripheral Blood Mononuclear Cells and platelets have been constructed from a cohort of 20 UC patients and 20 normal individuals. Through Significance Analysis of Microarrays, a signature of 31 differentially expressed platelet-derived miRNAs has been identified and biomarker performance estimated through a non-probabilistic binary linear classification using Support Vector Machines. Through this approach, classifier measurements reveal a predictive score of 92.8% accuracy, 96.2% specificity and 89.5% sensitivity in distinguishing UC patients from normal individuals. Additionally, the platelet-derived biomarker signature can be validated at 88% accuracy through qPCR assays, and a majority of the miRNAs in this panel can be demonstrated to sub-stratify into 4 highly correlated intensity based clusters. Analysis of predicted targets of these biomarkers reveal an enrichment of pathways associated with cytoskeleton assembly, transport, membrane permeability and regulation of transcription factors engaged in a variety of regulatory cascades that are consistent with a cell-mediated immune response model of intestinal inflammation. Interestingly, comparison of the miRNA biomarker panel and genetic loci implicated in IBD through genome-wide association studies identifies a physical linkage between hsa-miR-941 and a UC susceptibility loci located on Chr 20. Taken together, analysis of these expression maps outlines a promising catalog of novel platelet-derived miRNA biomarkers of clinical utility and provides insight into the potential biological function of these candidates in disease pathogenesis

Human Occupancy as a Source of Indoor Airborne Bacteria

Exposure to specific airborne bacteria indoors is linked to infectious and noninfectious adverse health outcomes. However, the sources and origins of bacteria suspended in indoor air are not well understood. This study presents evidence for elevated concentrations of indoor airborne bacteria due to human occupancy, and investigates the sources of these bacteria. Samples were collected in a university classroom while occupied and when vacant. The total particle mass concentration, bacterial genome concentration, and bacterial phylogenetic populations were characterized in indoor, outdoor, and ventilation duct supply air, as well as in the dust of ventilation system filters and in floor dust. Occupancy increased the total aerosol mass and bacterial genome concentration in indoor air PM10 and PM2.5 size fractions, with an increase of nearly two orders of magnitude in airborne bacterial genome concentration in PM10. On a per mass basis, floor dust was enriched in bacterial genomes compared to airborne particles. Quantitative comparisons between bacterial populations in indoor air and potential sources suggest that resuspended floor dust is an important contributor to bacterial aerosol populations during occupancy. Experiments that controlled for resuspension from the floor implies that direct human shedding may also significantly impact the concentration of indoor airborne particles. The high content of bacteria specific to the skin, nostrils, and hair of humans found in indoor air and in floor dust indicates that floors are an important reservoir of human-associated bacteria, and that the direct particle shedding of desquamated skin cells and their subsequent resuspension strongly influenced the airborne bacteria population structure in this human-occupied environment. Inhalation exposure to microbes shed by other current or previous human occupants may occur in communal indoor environments