Seasonal prediction skill of winter temperature over North India

This document is the Accepted Manuscript version of the following article: Tiwari, P.R., Kar, S.C., Mohanty, U.C. et al. Theor Appl Climatol (2016) 124: 15. The final publication is available at Springer via https://doi.org/10.1007/s00704-015-1397-y. © Springer-Verlag Wien 2015.The climatology, amplitude error, phase error, and mean square skill score (MSSS) of temperature predictions from five different state-of-the-art general circulation models (GCMs) have been examined for the winter (December–January– February) seasons over North India. In this region, temperature variability affects the phenological development processes of wheat crops and the grain yield. The GCM forecasts of temperature for a whole season issued in November from various organizations are compared with observed gridded temperature data obtained from the India Meteorological Department (IMD) for the period 1982–2009. The MSSS indicates that the models have skills of varying degrees. Predictions of maximum and minimum temperature obtained from the National Centers for Environmental Prediction (NCEP) climate forecast system model (NCEP_CFSv2) are compared with station level observations from the Snow and Avalanche Study Establishment (SASE). It has been found that when the model temperatures are corrected to account the bias in the model and actual orography, the predictions are able to delineate the observed trend compared to the trend without orography correction.Peer reviewedFinal Accepted Versio

The prevalence of triggers in paediatric migraine: a questionnaire study in 102 children and adolescents

The prevalence and characterization of migraine triggers have not been rigorously studied in children and adolescents. Using a questionnaire, we retrospectively studied the prevalence of 15 predefined trigger factors in a clinic-based population. In 102 children and adolescents fulfilling the Second Edition of The International Headache Classification criteria for paediatric migraine, at least one migraine trigger was reported by the patient and/or was the parents’ interpretation in 100% of patients. The mean number of migraine triggers reported per subject was 7. Mean time elapsed between exposure to a trigger factor and attack onset was comprised between 0 and 3 h in 88 patients (86%). The most common individual trigger was stress (75.5% of patients), followed by lack of sleep (69.6%), warm climate (68.6%) and video games (64.7%). Stress was also the most frequently reported migraine trigger always associated with attacks (24.5%). In conclusion, trigger factors were frequently reported by children and adolescents with migraine and stress was the most frequent

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

The effects of probiotic bacteria on glycaemic control in overweight men and women: a randomised controlled trial

Background/Objectives: Evidence from animal and in vitro models suggest a role of probiotic bacteria in improving glycaemic control and delaying the onset of type 2 diabetes. However, the evidence from controlled trials in humans is limited. The objective was to determine if the probiotic bacteria L. acidophilus La5 and B. animalis subsp lactis Bb12, supplemented in a whole food (yoghurt) or isolated (capsules) form, can improve biomarkers of glycaemic control. Subjects/methods: Following a 3-week washout period, 156 overweight men and women over 55 years (mean age: 67±8 years; mean body mass index (31±4 kg/m2) were randomized to a 6-week double-blinded parallel study. The four intervention groups were: (A) probiotic yoghurt plus probiotic capsules; (B) probiotic yoghurt plus placebo capsules; (C) control milk plus probiotic capsules; and (D) control milk plus placebo capsules. Outcome measurements, including fasting glucose, insulin, glycated haemoglobin and Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR), were performed at baseline and week 6. Results: Relative to the milk-control group, probiotic yoghurt resulted in a significantly higher HOMA-IR (0.32±0.15, P=0.038), but did not have a significant effect on the other three measures of glycaemic control (P>0.05). Relative to placebo capsules, probiotic capsules resulted in a significantly higher fasting glucose (0.15±0.07 mmol/l, P=0.037), with no significant effect on the other three measures of glycaemic control (P>0.05). Further analyses did not identify other variables as contributing to these adverse findings. Conclusions: Data from this study does not support the hypothesis that L. acidophilus La5 and B. animalis subsp lactis Bb12, either in isolated form or as part of a whole food, benefit short-term glycaemic control. Indeed, there is weak data for an adverse effect of these strains on glucose homoeostasis

Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines : a case report

Abstract Background Cancer vaccines can effectively establish clinically relevant tumor immunity. Novel sequencing approaches rapidly identify the mutational fingerprint of tumors, thus allowing to generate personalized tumor vaccines within a few weeks from diagnosis. Here, we report the case of a 62-year-old patient receiving a four-peptide-vaccine targeting the two sole mutations of his pancreatic tumor, identified via exome sequencing. Methods Vaccination started during chemotherapy in second complete remission and continued monthly thereafter. We tracked IFN-γ+ T cell responses against vaccine peptides in peripheral blood after 12, 17 and 34 vaccinations by analyzing T-cell receptor (TCR) repertoire diversity and epitope-binding regions of peptide-reactive T-cell lines and clones. By restricting analysis to sorted IFN-γ-producing T cells we could assure epitope-specificity, functionality, and TH1 polarization. Results A peptide-specific T-cell response against three of the four vaccine peptides could be detected sequentially. Molecular TCR analysis revealed a broad vaccine-reactive TCR repertoire with clones of discernible specificity. Four identical or convergent TCR sequences could be identified at more than one time-point, indicating timely persistence of vaccine-reactive T cells. One dominant TCR expressing a dual TCRVα chain could be found in three T-cell clones. The observed T-cell responses possibly contributed to clinical outcome: The patient is alive 6 years after initial diagnosis and in complete remission for 4 years now. Conclusions Therapeutic vaccination with a neoantigen-derived four-peptide vaccine resulted in a diverse and long-lasting immune response against these targets which was associated with prolonged clinical remission. These data warrant confirmation in a larger proof-of concept clinical trial

A Multi-Center Randomized Trial to Assess the Efficacy of Gatifloxacin versus Ciprofloxacin for the Treatment of Shigellosis in Vietnamese Children

The bacterial genus Shigella is the most common cause of dysentery (diarrhea containing blood and/or mucus) and the disease is common in developing countries with limitations in sanitation. Children are most at risk of infection and frequently require hospitalization and antimicrobial therapy. The WHO currently recommends the fluoroquinolone, ciprofloxacin, for the treatment of childhood Shigella infections. In recent years there has been a sharp increase in the number of organisms that exhibit resistance to nalidixic acid (an antimicrobial related to ciprofloxacin), corresponding with reduced susceptibility to ciprofloxacin. We hypothesized that infections with Shigella strains that demonstrate resistance to nalidixic acid may prevent effective treatment with ciprofloxacin. We performed a randomized controlled trial to compare 3 day ciprofloxacin therapy with 3 days of gatifloxacin, a newer generation fluoroquinolone with greater activity than ciprofloxacin. We measured treatment failure and time to the cessation of individual disease symptoms in 249 children with dysentery treated with gatifloxacin and 245 treated with ciprofloxacin. We could identify no significant differences in treatment failure between the two groups or in time to the cessation of individual symptoms. We conclude that, in Vietnam, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute dysentery

The Natural Product Domain Seeker NaPDoS: A Phylogeny Based Bioinformatic Tool to Classify Secondary Metabolite Gene Diversity

New bioinformatic tools are needed to analyze the growing volume of DNA sequence data. This is especially true in the case of secondary metabolite biosynthesis, where the highly repetitive nature of the associated genes creates major challenges for accurate sequence assembly and analysis. Here we introduce the web tool Natural Product Domain Seeker (NaPDoS), which provides an automated method to assess the secondary metabolite biosynthetic gene diversity and novelty of strains or environments. NaPDoS analyses are based on the phylogenetic relationships of sequence tags derived from polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, respectively. The sequence tags correspond to PKS-derived ketosynthase domains and NRPS-derived condensation domains and are compared to an internal database of experimentally characterized biosynthetic genes. NaPDoS provides a rapid mechanism to extract and classify ketosynthase and condensation domains from PCR products, genomes, and metagenomic datasets. Close database matches provide a mechanism to infer the generalized structures of secondary metabolites while new phylogenetic lineages provide targets for the discovery of new enzyme architectures or mechanisms of secondary metabolite assembly. Here we outline the main features of NaPDoS and test it on four draft genome sequences and two metagenomic datasets. The results provide a rapid method to assess secondary metabolite biosynthetic gene diversity and richness in organisms or environments and a mechanism to identify genes that may be associated with uncharacterized biochemistry