Increasing acceptance of chlorination for household water treatment: observations from Bangladesh

Point-of-use water treatment, especially chlorination, is an effective intervention to reduce diarrhoea, a leading cause of death for children under five. Yet success in chlorination uptake has been limited. One obstacle is objection to treated water's taste/odour. Protective chlorine residuals that are not offensive to users require accurate dosing - a challenge in practice. Further, taste sensitivity may be different for populations never exposed to chlorinated water. Here, household chlorination trials in Bangladesh similarly revealed dissatisfaction with treated water due to taste and odour, although attempts to quantify chlorine sensitivity disputed the dissatisfaction at lower residuals. A granular activated carbon (GAC) filter fitted to the spigot of a covered tank removed the remaining chlorine residual prior to drinking and increased user satisfaction. Such a filter removes taste as a barrier and allows over-dosing contaminated water to ensure disinfection, with implications for areas with high source water variability and for emergency situations

Influences on domestic well water testing behavior in a Central Maine area with frequent groundwater arsenic occurrence

In 2001 the Environmental Protection Agency (EPA) adopted a new standard for arsenic (As) in drinking water of 10 μg/L, replacing the old standard of 50 μg/L. However, for the 12% of the U.S. population relying on unregulated domestic well water, including half of the population of Maine, it is solely the well owner's responsibility to test and treat the water. A mailed household survey was implemented in January 2013 in 13 towns of Central Maine with the goal of understanding the population's testing and treatment practices and the key behavior influencing factors in an area with high well-water dependency and frequent natural groundwater As. The response rate was 58.3%; 525 of 900 likely-delivered surveys to randomly selected addresses were completed. Although 78% of the households reported that their well has been tested, half of it was more than 5 years ago. Among the 58.7% who believe they have tested for As, most do not remember the results. Better educated, higher income homeowners who more recently purchased their homes are most likely to have included As when last testing. While households agree that water and As-related health risks can be severe, they feel low personal vulnerability and there are low testing norms overall. Significant predictors of including As when last testing include: having knowledge that years of exposure increases As-related health risks (risk knowledge), knowing who to contact to test well water (action knowledge), believing that regular testing does not take too much time (instrumental attitude), and having neighbors who regularly test their water (descriptive norm). Homeowners in As-affected communities have the tendency to underestimate their As risks compared to their neighbors. The reasons for this optimistic bias require further study, but low testing behaviors in this area may be due to the influence of a combination of norm, ability, and attitude factors and barriers

Sanitation coverage in Bangladesh since the millennium: consistency matters

Household surveys in Bangladesh between 1994 and 2009 assessed sanitation access using questions that differed significantly over time, resulting in apparently inconsistent findings. Applying the WHO and UNICEF Joint Monitoring Programme's 2008 definition for open defecation and improved sanitation facilities excluding shared facilities to the compiled data set, sensible sanitation coverage trends emerge. The percentage of households openly defecating declined at a rate of about 1.8% per year from 30% in 1994 to 6.8% in 2009, primarily due to changes in rural areas. Access to individual improved sanitation facilities nearly doubled from about 30% in 2006 to 57% in 2009, with both rural and urban areas showing impressive progress. Access to shared improved latrines also nearly doubled from about 13% in 2006 to 24% in 2009, with the urban slums recording the greatest gain from 17% in 2006 to 65% in 2009. Shared improved latrines are only slightly less clean than individual ones. Dependence on shared improved latrines increases with population density. In 2007, 20% of the poorest households still openly defecated, although more of them (38%) shared a latrine of any type. A poverty reduction program is recommended to address this equity issue, although applying consistent definitions is crucial to documenting progress

Arsenic in tube well water in Bangladesh: health and economic impacts and implications for arsenic mitigation

A national drinking water quality survey conducted in 2009 furnished data that were used to make an updated estimate of chronic arsenic exposure in Bangladesh. About 20 million and 45 million people were found to be exposed to concentrations above the national standard of 50 μg/L and the World Health Organization’s guideline value of 10 μg/L, respectively. From the updated exposure data and all-cause mortality hazard ratios based on local epidemiological studies, it was estimated that arsenic exposures to concentrations > 50 μg/L and 10–50 μg/L account for an annual 24 000 and perhaps as many as 19 000 adult deaths in the country, respectively. Exposure varies widely in the 64 districts; among adults, arsenic-related deaths account for 0–15% of all deaths. An arsenic-related mortality rate of 1 in every 18 adult deaths could represent an economic burden of 13 billion United States dollars (US$) in lost productivity alone over the next 20 years. Arsenic mitigation should follow a two-tiered approach: (i) prioritizing provision of safe water to an estimated 5 million people exposed to > 200 μg/L arsenic, and (ii) building local arsenic testing capacity. The effectiveness of such an approach was demonstrated during the United Nations Children’s Fund 2006–2011 country programme, which provided safe water to arsenic-contaminated areas at a cost of US$ 11 per capita. National scale-up of such an approach would cost a few hundred million US dollars but would improve the health and productivity of the population, especially in future generations

Melanocortin-1 Receptor, Skin Cancer and Phenotypic Characteristics (M-SKIP) Project: Study Design and Methods for Pooling Results of Genetic Epidemiological Studies

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields

Quantifying sources of variability in infancy research using the infant-directed-speech preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure. (This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 798658.

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors