Cholera Outbreak Linked with Lack of Safe Water Supply Following a Tropical Cyclone in Pondicherry, India, 2012

In the aftermath of a severe cyclonic storm on 7 January 2012, a cluster of acute diarrhoea cases was reported from two localities in Pondicherry, Southern India. We investigated the outbreak to identify causes and recommend control measures. We defined a case as occurrence of diarrhoea of more than three loose stools per day with or without vomiting in a resident of affected areas during 6-18 January 2012. We used active (door-to-door survey) and stimulated passive (healthy facility-based) surveillance to identify cases. We described the outbreak by time, place, and person. We compared the case-patients with up to three controls without any apparent signs and symptoms of diarrhoea and matched for age, gender, and neighbourhood. We calculated matched odds ratio (MOR), 95% confidence intervals (CI), and population attributable fractions (PAF). We collected rectal swabs and water samples for laboratory diagnosis and tested water samples for microbiological quality. We identified 921 cases and one death among 8,367 residents (attack rate: 11%, case-fatality: 0.1%). The attack rate was the highest among persons of 50 years and above (14%) and females (12%). The outbreak started on 6 January and peaked on the 9th and lasted till 14 January. Cases were clustered around two major leakages in water supply system. Nine of the 16 stool samples yielded V. cholerae O1 Ogawa. We identified that consumption of water from the public distribution system (MOR=37, 95% CI 4.9-285, PAF: 97%), drinking unboiled water (MOR=35, 95% CI 4.5-269, PAF: 97%), and a common latrine used by two or more households (MOR=2.7, 95% CI 1.3-5.6) were independently associated with cholera. Epidemiological evidence suggested that this outbreak was due to ingestion of water contaminated by drainage following rains during cyclone. We recommended repair of the water supply lines, cleaning-up of the drains, handwashing, and drinking of boiled water

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Environmental Literacy for All Students: Evaluation of Environmental Science Courses Developed for a New Core Curriculum

Describes a course developed for undergraduate students that includes an environmental science lecture and laboratory section. Focuses on the laboratory section as the critical component with activities that are real-world related, hands-on, problem solving-based, and use cooperative learning approaches

Skeletal Muscle Protein Breakdown Remains Elevated in Pediatric Burn Survivors up to One-Year Post-Injury

Acute alterations in skeletal muscle protein metabolism are a well-established event associated with the stress response to burns. Nevertheless, the long-lasting effects of burn injury on skeletal muscle protein turnover are incompletely understood. This study was undertaken to investigate fractional synthesis (FSR) and breakdown (FBR) rates in skeletal muscle of pediatric burn patients (N=42, >30% total body surface area burns) for up to 1 year after injury. Skeletal muscle protein kinetics were measured in the postprandial state following bolus injections of (13)C(6) and (15)N phenylalanine stable isotopes. Plasma and muscle phenylalanine enrichments were quantified using gas chromatography-mass spectrometry. We found that the FSR in burn patients was 2- to 3-fold higher than values from healthy men previously reported in the literature (p≤0.05). The FBR was 4- to 6-fold higher than healthy values (p<0.01). Therefore, net protein balance was lower in burn patients compared to healthy men from 2 weeks to 12 months post injury (p<0.05). These findings show that skeletal muscle protein turnover stays elevated for up to 1 year after burn, an effect attributable to simultaneous increases in FBR and FSR. Muscle FBR exceeds FSR during this time, producing a persistent net negative protein balance, even in the postprandial state, which likely contributes to the prolonged cachexia seen in burned victims

Skeletal Muscle Protein Breakdown Remains Elevated in Pediatric Burn Survivors up to One-Year Post-Injury

Acute alterations in skeletal muscle protein metabolism are a well-established event associated with the stress response to burns. Nevertheless, the long-lasting effects of burn injury on skeletal muscle protein turnover are incompletely understood. This study was undertaken to investigate fractional synthesis (FSR) and breakdown (FBR) rates of protein in skeletal muscle of pediatric burn patients (n  =  42, &gt;30% total body surface area burns) for up to 1 year after injury. Skeletal muscle protein kinetics were measured in the post-prandial state following bolus injections of C6 and N phenylalanine stable isotopes. Plasma and muscle phenylalanine enrichments were quantified using gas chromatography-mass spectrometry. We found that the FSR in burn patients was 2- to 3-fold higher than values from healthy men previously reported in the literature (P ≤ 0.05). The FBR was 4- to 6-fold higher than healthy values (P  &lt;  0.01). Therefore, net protein balance was lower in burn patients compared with healthy men from 2 weeks to 12 months post-injury (P  &lt;  0.05). These findings show that skeletal muscle protein turnover stays elevated for up to 1 year after burn, an effect attributable to simultaneous increases in FBR and FSR. Muscle FBR exceeds FSR during this time, producing a persistent negative net protein balance, even in the post-prandial state, which likely contributes to the prolonged cachexia seen in burned victims