203 research outputs found
The inflationary trispectrum
We calculate the trispectrum of the primordial curvature perturbation
generated by an epoch of slow-roll inflation in the early universe, and
demonstrate that the non-gaussian signature imprinted at horizon crossing is
unobservably small, of order tau_NL < r/50, where r < 1 is the tensor-to-scalar
ratio. Therefore any primordial non-gaussianity observed in future microwave
background experiments is likely to have been synthesized by gravitational
effects on superhorizon scales. We discuss the application of Maldacena's
consistency condition to the trispectrum.Comment: 23 pages, 2 diagrams drawn with feynmp.sty, uses iopart.cls. v2,
replaced with version accepted by JCAP. Estimate of maximal tau_NL refined in
Section 5, resulting in smaller numerical value. Sign errors in Eq. (44) and
Eq. (48) corrected. Some minor notational change
Climate-sensitive health priorities in Nunatsiavut, Canada
Background: This exploratory study used participatory methods to identify, characterize, and rank climate-sensitive health priorities in Nunatsiavut, Labrador, Canada. Methods: A mixed method study design was used and involved collecting both qualitative and quantitative data at regional, community, and individual levels. In-depth interviews with regional health representatives were conducted throughout Nunatsiavut (n = 11). In addition, three PhotoVoice workshops were held with Rigolet community members (n = 11), where participants took photos of areas, items, or concepts that expressed how climate change is impacting their health. The workshop groups shared their photographs, discussed the stories and messages behind them, and then grouped photos into re-occurring themes. Two community surveys were administered in Rigolet to capture data on observed climatic and environmental changes in the area, and perceived impacts on health, wellbeing, and lifestyles (n = 187). Results: Climate-sensitive health pathways were described in terms of inter-relationships between environmental and social determinants of Inuit health. The climate-sensitive health priorities for the region included food security, water security, mental health and wellbeing, new hazards and safety concerns, and health services and delivery. Conclusions: The results highlight several climate-sensitive health priorities that are specific to the Nunatsiavut region, and suggest approaching health research and adaptation planning from an EcoHealth perspective
Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel
A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved
Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium
BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.
METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide.
RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.
CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia
Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis
Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18) and one strain of Paracoccidioides lutzii (Pb01). These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic species of Onygenales to transfer from soil to animal hosts.National Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health. Department of Health and Human Services (contract HHSN266200400001C)National Institutes of Health. Department of Health and Human Services(contract HHSN2722009000018C)Brazil. National Council for Scientific and Technological Developmen
The influence of active coping and perceived stress on health disparities in a multi-ethnic low income sample
<p>Abstract</p> <p>Background</p> <p>Extensive research has shown that ethnic health disparities are prevalent and many psychological and social factors influence health disparities. Understanding what factors influence health disparities and how to eliminate health disparities has become a major research objective. The purpose of this study was to examine the impact of coping style, stress, socioeconomic status (SES), and discrimination on health disparities in a large urban multi-ethnic sample.</p> <p>Methods</p> <p>Data from 894 participants were collected via telephone interviews. Independent variables included: coping style, SES, sex, perceived stress, and perceived discrimination. Dependent variables included self-rated general and oral health status. Data analysis included multiple linear regression modeling.</p> <p>Results</p> <p>Coping style was related to oral health for Blacks (B = .23, p < .05) and for Whites there was a significant interaction (B = -.59, p < .05) between coping style and SES for oral health. For Blacks, active coping was associated with better self-reported health. For Whites, low active coping coupled with low SES was significantly associated with worse oral health. Coping style was not significantly related to general health. Higher perceived stress was a significant correlate of poorer general health for all ethnoracial groups and poorer oral health for Hispanics and Blacks. SES was directly related to general health for Hispanics (.B = .27, p < .05) and Whites (B = .23, p < .05) but this relationship was mediated by perceived stress.</p> <p>Conclusion</p> <p>Our results indicate that perceived stress is a critical component in understanding health outcomes for all ethnoracial groups. While SES related significantly to general health for Whites and Hispanics, this relationship was mediated by perceived stress. Active coping was associated only with oral health.</p
A framework for human microbiome research
A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies
Morphology and Composition of the Surface of Mars: Mars Odyssey THEMIS Results
The Thermal Emission Imaging System (THEMIS) on Mars Odyssey has produced infrared to visible wavelength images of the martian surface that show lithologically distinct layers with variable thickness, implying temporal changes in the processes or environments during or after their formation. Kilometer-scale exposures of bedrock are observed; elsewhere airfall dust completely mantles the surface over thousands of square kilometers. Mars has compositional variations at 100-meter scales, for example, an exposure of olivine-rich basalt in the walls of Ganges Chasma. Thermally distinct ejecta facies occur around some craters with variations associated with crater age. Polar observations have identified temporal patches of water frost in the north polar cap. No thermal signatures associated with endogenic heat sources have been identified
Robust Reproducible Resting State Networks in the Awake Rodent Brain
Resting state networks (RSNs) have been studied extensively with functional MRI in humans in health and disease to reflect brain function in the un-stimulated state as well as reveal how the brain is altered with disease. Rodent models of disease have been used comprehensively to understand the biology of the disease as well as in the development of new therapies. RSN reported studies in rodents, however, are few, and most studies are performed with anesthetized rodents that might alter networks and differ from their non-anesthetized state. Acquiring RSN data in the awake rodent avoids the issues of anesthesia effects on brain function. Using high field fMRI we determined RSNs in awake rats using an independent component analysis (ICA) approach, however, ICA analysis can produce a large number of components, some with biological relevance (networks). We further have applied a novel method to determine networks that are robust and reproducible among all the components found with ICA. This analysis indicates that 7 networks are robust and reproducible in the rat and their putative role is discussed
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