Introduction of Routine Zinc Therapy for Children with Diarrhoea: Evaluation of Safety

On 8 May 2004, the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) recommended routine administration of zinc in the management of children, aged less than five years, with acute diarrhoea. In making the recommendation, WHO and UNICEF also suggested careful monitoring for adverse events associated with routine administration of zinc, particularly unusual or excess vomiting. The study assessed, in a phase IV trial, i.e. post-marketing surveillance of zinc, the occurrence of adverse events during the first hour after the administration of the first dose of zinc in children with acute or persistent diarrhoea. The study was conducted at the Dhaka Hospital of ICDDR,B and at an outpatient clinic operated by a local health NGO—Progoti Samaj Kallyan Protisthan (PSKP), Dhaka, Bangladesh. Eligible children, aged 3-59 months, were treated with 20 mg of zinc sulphate provided in a dispersible tablet formulation. The children were observed for 60 minutes following the initial treatment with zinc for adverse events, with particular attention given to vomiting or regurgitation. During the one-year observation period, 42,440 children (male 57% and female 43%) received zinc, and 20,246 (47.8%) of them were observed. Regurgitation and/or vomiting occurred in 4,392 (21.8%) of the children; 90.8% of these children had vomiting only once, 8.7% twice, and 0.5% more than twice. No children revisited the hospital for recurrent vomiting following their discharge. A significant proportion of infants and children may experience vomiting or regurgitation, usually once, following the administration of the first dose of zinc. This is a transient phenomenon that did not impact on continuation of treatment with zinc

Universality in D-brane Inflation

We study the six-field dynamics of D3-brane inflation for a general scalar potential on the conifold, finding simple, universal behavior. We numerically evolve the equations of motion for an ensemble of more than 7 \times 10^7 realizations, drawing the coefficients in the scalar potential from statistical distributions whose detailed properties have demonstrably small effects on our results. When prolonged inflation occurs, it has a characteristic form: the D3-brane initially moves rapidly in the angular directions, spirals down to an inflection point in the potential, and settles into single-field inflation. The probability of N_{e} e-folds of inflation is a power law, P(N_{e}) \propto N_{e}^{-3}, and we derive the same exponent from a simple analytical model. The success of inflation is relatively insensitive to the initial conditions: we find attractor behavior in the angular directions, and the D3-brane can begin far above the inflection point without overshooting. In favorable regions of the parameter space, models yielding 60 e-folds of expansion arise approximately once in 10^3 trials. Realizations that are effectively single-field and give rise to a primordial spectrum of fluctuations consistent with WMAP, for which at least 120 e-folds are required, arise approximately once in 10^5 trials. The emergence of robust predictions from a six-field potential with hundreds of terms invites an analytic approach to multifield inflation.Comment: 28 pages, 9 figure

Kahler moduli double inflation

We show that double inflation is naturally realized in K\"ahler moduli inflation, which is caused by moduli associated with string compactification. We find that there is a small coupling between the two inflatons which leads to amplification of perturbations through parametric resonance in the intermediate stage of double inflation. This results in the appearance of a peak in the power spectrum of the primordial curvature perturbation. We numerically calculate the power spectrum and show that the power spectrum can have a peak on observationally interesing scales. We also compute the TT-spectrum of CMB based on the power spectrum with a peak and see that it better fits WMAP 7-years data.Comment: 21 pages, 8 figure

Semiclassical relations and IR effects in de Sitter and slow-roll space-times

We calculate IR divergent graviton one-loop corrections to scalar correlators in de Sitter space, and show that the leading IR contribution may be reproduced via simple semiclassical consistency relations. One can likewise use such semiclassical relations to calculate leading IR corrections to correlators in slow-roll inflation. The regulated corrections shift the tensor/scalar ratio and consistency relation of single field inflation, and non-gaussianity parameters averaged over very large distances. For inflation of sufficient duration, for example arising from a chaotic inflationary scenario, these corrections become of order unity. First-order corrections of this size indicate a breakdown of the perturbative expansion, and suggest the need for a non-perturbative description of the corresponding regime. This is analogous to a situation argued to arise in black hole evolution, and to interfere with a sharp perturbative calculation of "missing information" in Hawking radiation.Comment: 32 pages, 2 figures; v2: running of spectral index included and other minor changes; v3: minor changes to agree with published versio

Features of heavy physics in the CMB power spectrum

The computation of the primordial power spectrum in multi-field inflation models requires us to correctly account for all relevant interactions between adiabatic and non-adiabatic modes around and after horizon crossing. One specific complication arises from derivative interactions induced by the curvilinear trajectory of the inflaton in a multi-dimensional field space. In this work we compute the power spectrum in general multi-field models and show that certain inflaton trajectories may lead to observationally significant imprints of `heavy' physics in the primordial power spectrum if the inflaton trajectory turns, that is, traverses a bend, sufficiently fast (without interrupting slow roll), even in cases where the normal modes have masses approaching the cutoff of our theory. We emphasise that turning is defined with respect to the geodesics of the sigma model metric, irrespective of whether this is canonical or non-trivial. The imprints generically take the form of damped superimposed oscillations on the power spectrum. In the particular case of two-field models, if one of the fields is sufficiently massive compared to the scale of inflation, we are able to compute an effective low energy theory for the adiabatic mode encapsulating certain relevant operators of the full multi-field dynamics. As expected, a particular characteristic of this effective theory is a modified speed of sound for the adiabatic mode which is a functional of the background inflaton trajectory and the turns traversed during inflation. Hence in addition, we expect non-Gaussian signatures directly related to the features imprinted in the power spectrum.Comment: 41 pages, 6 figures, references updated, minor modifications. Version to appear in JCAP. v4: Equations (4.28) and (4.30) and Figures 5 and 6 correcte

Pairing in two-dimensional boson-fermion mixtures

The possibilities of pairing in two-dimensional boson-fermion mixtures are carefully analyzed. It is shown that the boson-induced attraction between two identical fermions dominates the p-wave pairing at low density. For a given fermion density, the pairing gap becomes maximal at a certain optimal boson concentration. The conditions for observing pairing in current experiments are discussedComment: 10 pages, 5 figs, revtex

Large slow-roll corrections to the bispectrum of noncanonical inflation

Nongaussian statistics are a powerful discriminant between inflationary models, particularly those with noncanonical kinetic terms. Focusing on theories where the Lagrangian is an arbitrary Lorentz-invariant function of a scalar field and its first derivatives, we review and extend the calculation of the observable three-point function. We compute the "next-order" slow-roll corrections to the bispectrum in closed form, and obtain quantitative estimates of their magnitude in DBI and power-law k-inflation. In the DBI case our results enable us to estimate corrections from the shape of the potential and the warp factor: these can be of order several tens of percent. We track the possible sources of large logarithms which can spoil ordinary perturbation theory, and use them to obtain a general formula for the scale dependence of the bispectrum. Our result satisfies the next-order version of Maldacena's consistency condition and an equivalent consistency condition for the scale dependence. We identify a new bispectrum shape available at next-order, which is similar to a shape encountered in Galileon models. If fNL is sufficiently large this shape may be independently detectable.Comment: v1: 37 pages, plus tables, figures and appendices. v2: supersedes version published in JCAP; some clarifications and more detailed comparison with earlier literature. All results unchanged. v3:improvements to some plots; text unchange

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

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

Background: 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