Effect of household-based drinking water chlorination on diarrhoea among children under five in Orissa, India: a double-blind randomised placebo-controlled trial.

BACKGROUND: Boiling, disinfecting, and filtering water within the home can improve the microbiological quality of drinking water among the hundreds of millions of people who rely on unsafe water supplies. However, the impact of these interventions on diarrhoea is unclear. Most studies using open trial designs have reported a protective effect on diarrhoea while blinded studies of household water treatment in low-income settings have found no such effect. However, none of those studies were powered to detect an impact among children under five and participants were followed-up over short periods of time. The aim of this study was to measure the effect of in-home water disinfection on diarrhoea among children under five. METHODS AND FINDINGS: We conducted a double-blind randomised controlled trial between November 2010 and December 2011. The study included 2,163 households and 2,986 children under five in rural and urban communities of Orissa, India. The intervention consisted of an intensive promotion campaign and free distribution of sodium dichloroisocyanurate (NaDCC) tablets during bi-monthly households visits. An independent evaluation team visited households monthly for one year to collect health data and water samples. The primary outcome was the longitudinal prevalence of diarrhoea (3-day point prevalence) among children aged under five. Weight-for-age was also measured at each visit to assess its potential as a proxy marker for diarrhoea. Adherence was monitored each month through caregiver's reports and the presence of residual free chlorine in the child's drinking water at the time of visit. On 20% of the total household visits, children's drinking water was assayed for thermotolerant coliforms (TTC), an indicator of faecal contamination. The primary analysis was on an intention-to-treat basis. Binomial regression with a log link function and robust standard errors was used to compare prevalence of diarrhoea between arms. We used generalised estimating equations to account for clustering at the household level. The impact of the intervention on weight-for-age z scores (WAZ) was analysed using random effect linear regression. Over the follow-up period, 84,391 child-days of observations were recorded, representing 88% of total possible child-days of observation. The longitudinal prevalence of diarrhoea among intervention children was 1.69% compared to 1.74% among controls. After adjusting for clustering within household, the prevalence ratio of the intervention to control was 0.95 (95% CI 0.79-1.13). The mean WAZ was similar among children of the intervention and control groups (-1.586 versus -1.589, respectively). Among intervention households, 51% reported their child's drinking water to be treated with the tablets at the time of visit, though only 32% of water samples tested positive for residual chlorine. Faecal contamination of drinking water was lower among intervention households than controls (geometric mean TTC count of 50 [95% CI 44-57] per 100 ml compared to 122 [95% CI 107-139] per 100 ml among controls [p<0.001] [n = 4,546]). CONCLUSIONS: Our study was designed to overcome the shortcomings of previous double-blinded trials of household water treatment in low-income settings. The sample size was larger, the follow-up period longer, both urban and rural populations were included, and adherence and water quality were monitored extensively over time. These results provide no evidence that the intervention was protective against diarrhoea. Low compliance and modest reduction in water contamination may have contributed to the lack of effect. However, our findings are consistent with other blinded studies of similar interventions and raise additional questions about the actual health impact of household water treatment under these conditions. TRIAL REGISTRATION: ClinicalTrials.govNCT01202383 Please see later in the article for the Editors' Summary

Variation in Tropical Reef Symbiont Metagenomes Defined by Secondary Metabolism

The complex evolution of secondary metabolism is important in biology, drug development, and synthetic biology. To examine this problem at a fine scale, we compared the genomes and chemistry of 24 strains of uncultivated cyanobacteria, Prochloron didemni, that live symbiotically with tropical ascidians and that produce natural products isolated from the animals. Although several animal species were obtained along a >5500 km transect of the Pacific Ocean, P. didemni strains are >97% identical across much of their genomes, with only a few exceptions concentrated in secondary metabolism. Secondary metabolic gene clusters were sporadically present or absent in identical genomic locations with no consistent pattern of co-occurrence. Discrete mutations were observed, leading to new chemicals that we isolated from animals. Functional cassettes encoding diverse chemicals are exchanged among a single population of symbiotic P. didemni that spans the tropical Pacific, providing the host animals with a varying arsenal of secondary metabolites

Annotation extensions

The specificity of knowledge that Gene Ontology (GO) annotations currently can represent is still restricted by the legacy format of the GO annotation file, a format intentionally designed for simplicity to keep the barriers to entry low and thus encourage initial adoption. Historically, the information that could be captured in a GO annotation was simply the role or location of a gene product, although genetically interacting or binding partners could be specified. While there was no mechanism within the original GO annotation format for capturing additional information about the context of a GO term, such as the target gene of an activity or the location of a molecular function, the long-term vision for the GO Consortium was to provide greater expressivity in its annotations to capture physiologically relevant information. Thus, as a step forwards, the GO Consortium has introduced a new field into the annotation format, annotation extensions, which can be used to capture valuable contextual detail. This provides experimentally verified links between gene products and other physiological information that is crucial for accurate analysis of pathway and network data. This chapter will provide a simple overview of annotation extensions, illustrated with examples of their usage, and explain why they are useful for scientists and bioinformaticians alike

The impact of avoiding cardiopulmonary by-pass during coronary artery bypass surgery in elderly patients: the Danish On-pump Off-pump Randomisation Study (DOORS)

<p>Abstract</p> <p>Background</p> <p>Coronary Artery Bypass Graft operation for ischemic heart disease provides improved quality of life and, in some patients, prolonged survival. Concern has, however, been raised about complications that may be related to the use of cardiopulmonary by-pass (CPB) and aortic cross-clamping. It has been hypothesized that when coronary artery by-pass grafting is performed without the use of CPB, the rate of serious complications is reduced.</p> <p>Methods/Design</p> <p>The trial is designed as an open, randomized, controlled, clinical trial with blinded assessment of end-points. Patients at or above 70 years of age, referred for surgical myocardial revascularisation, are included and randomised to receive coronary artery by-pass grafting either with or without the use of CPB and aortic cross-clamping. Follow-up is performed by clinical, biochemical, electrocardiographic, and angiographic data that are evaluated by independent committees that are blinded with respect to the result of the randomisation. End points include mortality, stroke, myocardial infarction, graft patency, quality of life, and cost-effectiveness. The trial is performed in four different Danish, cardiac surgery centres.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00123981</p

Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure

CBESW: Sequence Alignment on the Playstation 3

<p>Abstract</p> <p>Background</p> <p>The exponential growth of available biological data has caused bioinformatics to be rapidly moving towards a data-intensive, computational science. As a result, the computational power needed by bioinformatics applications is growing exponentially as well. The recent emergence of accelerator technologies has made it possible to achieve an excellent improvement in execution time for many bioinformatics applications, compared to current general-purpose platforms. In this paper, we demonstrate how the PlayStation^®3, powered by the Cell Broadband Engine, can be used as a computational platform to accelerate the Smith-Waterman algorithm.</p> <p>Results</p> <p>For large datasets, our implementation on the PlayStation^®3 provides a significant improvement in running time compared to other implementations such as SSEARCH, Striped Smith-Waterman and CUDA. Our implementation achieves a peak performance of up to 3,646 MCUPS.</p> <p>Conclusion</p> <p>The results from our experiments demonstrate that the PlayStation^®3 console can be used as an efficient low cost computational platform for high performance sequence alignment applications.</p

The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis

Tofisopam is a member of the 2,3-benzodiazepine compound family which is marketed for the treatment of anxiety in some European countries. In contrast to classical 1,4-benzodiazepines, the compound does not bind to the benzodiazepine binding site of the γ-aminobutyric acid receptor and its psychopharmacological profile differs from such compounds. In addition to anxiolytic properties, antipsychotic effects are reported. We now show that tofisopam, 50 mg/kg intraperitoneally (i.p.), administered in parallel to repeated doses of dizocilpine 0.2 mg/kg i.p. can ameliorate dizocilpine-induced prolongation of immobility, which is considered to be a model of negative symptoms of psychosis. We further show that tofisopam acts as an isoenzyme-selective inhibitor of phosphodiesterases (PDEs) with highest affinity to PDE-4A1 (0.42 μM) followed by PDE-10A1 (0.92 μM), PDE-3 (1.98 μM) and PDE-2A3 (2.11 μM). The data indicate that tofisopam is an interesting candidate for the adjuvant treatment of psychosis with focus on negative symptoms. Combined partial inhibition of PDE-4 and PDE-10 as well as PDE-2 may be the underlying mechanism to this activity. Due to the good safety profile of tofisopam as evident from long-term use of this agent in patients, it may be concluded that dual or triple inhibition of PDE isoenzymes with additive or synergistic effects may be an interesting approach to pharmacological activity, resulting in active compounds with beneficial safety profile. Dose-limiting side effects such as emesis induced by selective inhibition of PDE-4 may be prevented by such strategies

High Adherence Is Necessary to Realize Health Gains from Water Quality Interventions

BACKGROUND: Safe drinking water is critical for health. Household water treatment (HWT) has been recommended for improving access to potable water where existing sources are unsafe. Reports of low adherence to HWT may limit the usefulness of this approach, however. METHODS AND FINDINGS: We constructed a quantitative microbial risk model to predict gains in health attributable to water quality interventions based on a range of assumptions about pre-treatment water quality; treatment effectiveness in reducing bacteria, viruses, and protozoan parasites; adherence to treatment interventions; volume of water consumed per person per day; and other variables. According to mean estimates, greater than 500 DALYs may be averted per 100,000 person-years with increased access to safe water, assuming moderately poor pre-treatment water quality that is a source of risk and high treatment adherence (>90% of water consumed is treated). A decline in adherence from 100% to 90% reduces predicted health gains by up to 96%, with sharpest declines when pre-treatment water quality is of higher risk. CONCLUSIONS: Results suggest that high adherence is essential in order to realize potential health gains from HWT

CRISPR Recognition Tool (CRT): a tool for automatic detection of clustered regularly interspaced palindromic repeats

<p>Abstract</p> <p>Background</p> <p>Clustered Regularly Interspaced Palindromic Repeats (CRISPRs) are a novel type of direct repeat found in a wide range of bacteria and archaea. CRISPRs are beginning to attract attention because of their proposed mechanism; that is, defending their hosts against invading extrachromosomal elements such as viruses. Existing repeat detection tools do a poor job of identifying CRISPRs due to the presence of unique spacer sequences separating the repeats. In this study, a new tool, CRT, is introduced that rapidly and accurately identifies CRISPRs in large DNA strings, such as genomes and metagenomes.</p> <p>Results</p> <p>CRT was compared to CRISPR detection tools, Patscan and Pilercr. In terms of correctness, CRT was shown to be very reliable, demonstrating significant improvements over Patscan for measures precision, recall and quality. When compared to Pilercr, CRT showed improved performance for recall and quality. In terms of speed, CRT proved to be a huge improvement over Patscan. Both CRT and Pilercr were comparable in speed, however CRT was faster for genomes containing large numbers of repeats.</p> <p>Conclusion</p> <p>In this paper a new tool was introduced for the automatic detection of CRISPR elements. This tool, CRT, showed some important improvements over current techniques for CRISPR identification. CRT's approach to detecting repetitive sequences is straightforward. It uses a simple sequential scan of a DNA sequence and detects repeats directly without any major conversion or preprocessing of the input. This leads to a program that is easy to describe and understand; yet it is very accurate, fast and memory efficient, being O(<it>n</it>) in space and O(<it>nm</it>/<it>l</it>) in time.</p

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012