Showing papers by "University of Connecticut published in 2015"

Integrative analysis of 111 reference human epigenomes

Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Accelerating extinction risk from climate change

Abstract: Current predictions of extinction risks from climate change vary widely depending on the specific assumptions and geographic and taxonomic focus of each study. I synthesized published studies in order to estimate a global mean extinction rate and determine which factors contribute the greatest uncertainty to climate change–induced extinction risks. Results suggest that extinction risks will accelerate with future global temperatures, threatening up to one in six species under current policies. Extinction risks were highest in South America, Australia, and New Zealand, and risks did not vary by taxonomic group. Realistic assumptions about extinction debt and dispersal capacity substantially increased extinction risks. We urgently need to adopt strategies that limit further climate change if we are to avoid an acceleration of global extinctions.

The Performance of RMSEA in Models With Small Degrees of Freedom

Abstract: Given that the root mean square error of approximation (RMSEA) is currently one of the most popular measures of goodness-of-model fit within structural equation modeling (SEM), it is important to know how well the RMSEA performs in models with small degrees of freedom (df). Unfortunately, most previous work on the RMSEA and its confidence interval has focused on models with a large df. Building on the work of Chen et al. to examine the impact of small df on the RMSEA, we conducted a theoretical analysis and a Monte Carlo simulation using correctly specified models with varying df and sample size. The results of our investigation indicate that when the cutoff values are used to assess the fit of the properly specified models with small df and small sample size, the RMSEA too often falsely indicates a poor fitting model. We recommend not computing the RMSEA for small df models, especially those with small sample sizes, but rather estimating parameters that were not originally specified in the model.

spThin: an R package for spatial thinning of species occurrence records for use in ecological niche models

Abstract: Spatial thinning of species occurrence records can help address problems associated with spatial sampling biases. Ideally, thinning removes the fewest records necessary to substantially reduce the effects of sampling bias, while simultaneously retaining the greatest amount of useful information. Spatial thinning can be done manually; however, this is prohibitively time consuming for large datasets. Using a randomization approach, the ‘thin’ function in the spThin R package returns a dataset with the maximum number of records for a given thinning distance, when run for sufficient iterations. We here provide a worked example for the Caribbean spiny pocket mouse, where the results obtained match those of manual thinning.

Horizontal gene transfer: building the web of life.

Abstract: Horizontal gene transfer (HGT) is the sharing of genetic material between organisms that are not in a parent-offspring relationship. HGT is a widely recognized mechanism for adaptation in bacteria and archaea. Microbial antibiotic resistance and pathogenicity are often associated with HGT, but the scope of HGT extends far beyond disease-causing organisms. In this Review, we describe how HGT has shaped the web of life using examples of HGT among prokaryotes, between prokaryotes and eukaryotes, and even between multicellular eukaryotes. We discuss replacement and additive HGT, the proposed mechanisms of HGT, selective forces that influence HGT, and the evolutionary impact of HGT on ancestral populations and existing populations such as the human microbiome.

Fluorescence based explosive detection: from mechanisms to sensory materials.

Abstract: The detection of explosives is one of the current pressing concerns in global security. In the past few decades, a large number of emissive sensing materials have been developed for the detection of explosives in vapor, solution, and solid states through fluorescence methods. In recent years, great efforts have been devoted to develop new fluorescent materials with various sensing mechanisms for detecting explosives in order to achieve super-sensitivity, ultra-selectivity, as well as fast response time. This review article starts with a brief introduction on various sensing mechanisms for fluorescence based explosive detection, and then summarizes in an exhaustive and systematic way the state-of-the-art of fluorescent materials for explosive detection with a focus on the research in the recent 5 years. A wide range of fluorescent materials, such as conjugated polymers, small fluorophores, supramolecular systems, bio-inspired materials and aggregation induced emission-active materials, and their sensing performance and sensing mechanism are the centerpiece of this review. Finally, conclusions and future outlook are presented and discussed.

National Athletic Trainers' Association Position Statement: Exertional Heat Illnesses

Abstract: Objective: To present best-practice recommendations for the prevention, recognition, and treatment of exertional heat illnesses (EHIs) and to describe the relevant physiology of thermoregulation. ...

Minimum Information about a Biosynthetic Gene cluster.

Abstract: A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.

Pediatric Acute Respiratory Distress Syndrome: Consensus Recommendations From the Pediatric Acute Lung Injury Consensus Conference

Abstract: Objective: To describe the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. Design: Consensus conference of experts in pediatric acute lung injury. Setting: Not applicable. Subjects: PICU patients with evidence of acute lung injury or acute respiratory distress syndrome. Interventions: None. Methods: A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published, data were lacking a modified Delphi approach emphasizing strong professional agreement was used. Measurements and Main Results: A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published data were lacking a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the following topics related to pediatric acute respiratory distress syndrome: 1) Definition, prevalence, and epidemiology; 2) Pathophysiology, comorbidities, and severity; 3) Ventilatory support; 4) Pulmonary-specific ancillary treatment; 5) Nonpulmonary treatment; 6) Monitoring; 7) Noninvasive support and ventilation; 8) Extracorporeal support; and 9) Morbidity and long-term outcomes. There were 132 recommendations with strong agreement and 19 recommendations with weak agreement. Once restated, the final iteration of the recommendations had none with equipoise or disagreement. Conclusions: The Consensus Conference developed pediatric-specific definitions for acute respiratory distress syndrome and recommendations regarding treatment and future research priorities. These are intended to promote optimization and consistency of care for children with pediatric acute respiratory distress syndrome and identify areas of uncertainty requiring further investigation.

The nature of social dominance orientation: Theorizing and measuring preferences for intergroup inequality using the new SDO₇ scale.

Abstract: A new conceptualization and measurement of social dominance orientation-individual differences in the preference for group based hierarchy and inequality-is introduced. In contrast to previous measures of social dominance orientation that were designed to be unidimensional, the new measure (SDO7) embeds theoretically grounded subdimensions of SDO-SDO-Dominance (SDO-D) and SDO-Egalitarianism (SDO-E). SDO-D constitutes a preference for systems of group-based dominance in which high status groups forcefully oppress lower status groups. SDO-E constitutes a preference for systems of group-based inequality that are maintained by an interrelated network of subtle hierarchy-enhancing ideologies and social policies. Confirmatory factor and criterion validity analyses confirmed that SDO-D and SDO-E are theoretically distinct and dissociate in terms of the intergroup outcomes they best predict. For the first time, distinct personality and individual difference bases of SDO-D and SDO-E are outlined. We clarify the construct validity of SDO by strictly assessing a preference for dominance hierarchies in general, removing a possible confound relating to support for hierarchy benefitting the ingroup. Consistent with this, results show that among members of a disadvantaged ethnic minority group (African Americans), endorsement of SDO7 is inversely related to ingroup identity. We further demonstrate these effects using nationally representative samples of U.S. Blacks and Whites, documenting the generalizability of these findings. Finally, we introduce and validate a brief 4-item measure of each dimension. This article importantly extends our theoretical understanding of one of the most generative constructs in social psychology, and introduces powerful new tools for its measurement.

Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis

Abstract: BackgroundEarly clinical studies suggested that the anti–interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis. MethodsIn two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician’s global assessment ...

Climate change impacts on bumblebees converge across continents

Abstract: For many species, geographical ranges are expanding toward the poles in response to climate change, while remaining stable along range edges nearest the equator. Using long-term observations across Europe and North America over 110 years, we tested for climate change–related range shifts in bumblebee species across the full extents of their latitudinal and thermal limits and movements along elevation gradients. We found cross-continentally consistent trends in failures to track warming through time at species’ northern range limits, range losses from southern range limits, and shifts to higher elevations among southern species. These effects are independent of changing land uses or pesticide applications and underscore the need to test for climate impacts at both leading and trailing latitudinal and thermal limits for species.

Early Intervention for Children With Autism Spectrum Disorder Under 3 Years of Age: Recommendations for Practice and Research

Abstract: This article reviews current evidence for autism spectrum disorder (ASD) interventions for children aged <3 years, based on peer-reviewed articles published up to December 2013. Several groups have adapted treatments initially designed for older, preschool-aged children with ASD, integrating best practice in behavioral teaching methods into a developmental framework based on current scientific understanding of how infants and toddlers learn. The central role of parents has been emphasized, and interventions are designed to incorporate learning opportunities into everyday activities, capitalize on "teachable moments," and facilitate the generalization of skills beyond the familiar home setting. Our review identified several comprehensive and targeted treatment models with evidence of clear benefits. Although some trials were limited to 8- to 12-week outcome data, enhanced outcomes associated with some interventions were evaluated over periods as long as 2 years. Based on this review, recommendations are proposed for clinical practice and future research.

The global distribution of diet breadth in insect herbivores

Abstract: Understanding variation in resource specialization is important for progress on issues that include coevolution, community assembly, ecosystem processes, and the latitudinal gradient of species richness. Herbivorous insects are useful models for studying resource specialization, and the interaction between plants and herbivorous insects is one of the most common and consequential ecological associations on the planet. However, uncertainty persists regarding fundamental features of herbivore diet breadth, including its relationship to latitude and plant species richness. Here, we use a global dataset to investigate host range for over 7,500 insect herbivore species covering a wide taxonomic breadth and interacting with more than 2,000 species of plants in 165 families. We ask whether relatively specialized and generalized herbivores represent a dichotomy rather than a continuum from few to many host families and species attacked and whether diet breadth changes with increasing plant species richness toward the tropics. Across geographic regions and taxonomic subsets of the data, we find that the distribution of diet breadth is fit well by a discrete, truncated Pareto power law characterized by the predominance of specialized herbivores and a long, thin tail of more generalized species. Both the taxonomic and phylogenetic distributions of diet breadth shift globally with latitude, consistent with a higher frequency of specialized insects in tropical regions. We also find that more diverse lineages of plants support assemblages of relatively more specialized herbivores and that the global distribution of plant diversity contributes to but does not fully explain the latitudinal gradient in insect herbivore specialization.

Updating ACSM's Recommendations for Exercise Preparticipation Health Screening

Abstract: The purpose of the American College of Sports Medicine's (ACSM) exercise preparticipation health screening process is to identify individuals who may be at elevated risk for exercise-related sudden cardiac death and/or acute myocardial infarction. Recent studies have suggested that using the current ACSM exercise preparticipation health screening guidelines can result in excessive physician referrals, possibly creating a barrier to exercise participation. In addition, there is considerable evidence that exercise is safe for most people and has many associated health and fitness benefits; exercise-related cardiovascular events are often preceded by warning signs/symptoms; and the cardiovascular risks associated with exercise lessen as individuals become more physically active/fit. Consequently, a scientific roundtable was convened by the ACSM in June 2014 to evaluate the current exercise preparticipation health screening recommendations. The roundtable proposed a new evidence-informed model for exercise preparticipation health screening on the basis of three factors: 1) the individual's current level of physical activity, 2) presence of signs or symptoms and/or known cardiovascular, metabolic, or renal disease, and 3) desired exercise intensity, as these variables have been identified as risk modulators of exercise-related cardiovascular events. Identifying cardiovascular disease risk factors remains an important objective of overall disease prevention and management, but risk factor profiling is no longer included in the exercise preparticipation health screening process. The new ACSM exercise preparticipation health screening recommendations reduce possible unnecessary barriers to adopting and maintaining a regular exercise program, a lifestyle of habitual physical activity, or both, and thereby emphasize the important public health message that regular physical activity is important for all individuals.

Constraints on the evolution of phenotypic plasticity: limits and costs of phenotype and plasticity

Abstract: Phenotypic plasticity is ubiquitous and generally regarded as a key mechanism for enabling organisms to survive in the face of environmental change Because no organism is infinitely or ideally plastic, theory suggests that there must be limits (for example, the lack of ability to produce an optimal trait) to the evolution of phenotypic plasticity, or that plasticity may have inherent significant costs Yet numerous experimental studies have not detected widespread costs Explicitly differentiating plasticity costs from phenotype costs, we re-evaluate fundamental questions of the limits to the evolution of plasticity and of generalists vs specialists We advocate for the view that relaxed selection and variable selection intensities are likely more important constraints to the evolution of plasticity than the costs of plasticity Some forms of plasticity, such as learning, may be inherently costly In addition, we examine opportunities to offset costs of phenotypes through ontogeny, amelioration of phenotypic costs across environments, and the condition-dependent hypothesis We propose avenues of further inquiry in the limits of plasticity using new and classic methods of ecological parameterization, phylogenetics and omics in the context of answering questions on the constraints of plasticity Given plasticity's key role in coping with environmental change, approaches spanning the spectrum from applied to basic will greatly enrich our understanding of the evolution of plasticity and resolve our understanding of limits

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.

Abstract: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Prevalence of Internet gaming disorder in German adolescents: diagnostic contribution of the nine DSM-5 criteria in a state-wide representative sample.

Abstract: Background and aims Internet gaming disorder (IGD) is included as a condition for further study in Section 3 of the DSM-5. Nine criteria were proposed with a threshold of five or more criteria recommended for diagnosis. The aims of this study were to assess how the specific criteria contribute to diagnosis and to estimate prevalence rates of IGD based on DSM-5 recommendations. Design Large-scale, state-representative school survey using a standardized questionnaire. Setting Germany (Lower Saxony). Participants A total of 11 003 ninth-graders aged 13–18 years (mean = 14.88, 51.09% male). Measurements IGD was assessed with a DSM-5 adapted version of the Video Game Dependency Scale that covered all nine criteria of IGD. Findings In total, 1.16% [95% confidence interval (CI) = 0.96, 1.36] of respondents were classified with IGD according to DSM-5 recommendations. IGD students played games for longer periods, skipped school more often, had lower grades in school, reported more sleep problems and more often endorsed feeling ‘addicted to gaming’ than their non-IGD counterparts. The most frequently reported DSM-5 criteria overall were ‘escape adverse moods’ (5.30%) and ‘preoccupation’ (3.91%), but endorsement of these criteria rarely related to IGD diagnosis. Conditional inference trees showed that the criteria ‘give up other activities’, ‘tolerance’ and ‘withdrawal’ were of key importance for identifying IGD as defined by DSM-5. Conclusions Based on a state-wide representative school survey in Germany, endorsement of five or more criteria of DSM-5 internet gaming disorder (IGD) occurred in 1.16% of the students, and these students evidence greater impairment compared with non-IGD students. Symptoms related to ‘give up other activities’, ‘tolerance’ and ‘withdrawal’ are most relevant for IGD diagnosis in this age group.

Spatial patterns of solar photovoltaic system adoption: The influence of neighbors and the built environment

Abstract: The diffusion of new technologies is often mediated by spatial and socioeconomic factors. This article empirically examines the diffusion of an important renewable energy technology: residential solar photovoltaic (PV) systems. Using detailed data on PV installations in Connecticut, we identify the spatial patterns of diffusion, which indicate considerable clustering of adoptions. This clustering does not simply follow the spatial distribution of income or population. We find that smaller centers contribute to adoption more than larger urban areas, in a wave-like centrifugal pattern. Our empirical estimation demonstrates a strong relationship between adoption and the number of nearby previously installed systems as well as built environment and policy variables. The effect of nearby systems diminishes with distance and time, suggesting a spatial neighbor effect conveyed through social interaction and visibility. These results disentangle the process of diffusion of PV systems and provide guidance to stakeholders in the solar market.

The Symbiodinium kawagutii genome illuminates dinoflagellate gene expression and coral symbiosis

Abstract: Dinoflagellates are important components of marine ecosystems and essential coral symbionts, yet little is known about their genomes. We report here on the analysis of a high-quality assembly from the 1180-megabase genome of Symbiodinium kawagutii. We annotated protein-coding genes and identified Symbiodinium-specific gene families. No whole-genome duplication was observed, but instead we found active (retro)transposition and gene family expansion, especially in processes important for successful symbiosis with corals. We also documented genes potentially governing sexual reproduction and cyst formation, novel promoter elements, and a microRNA system potentially regulating gene expression in both symbiont and coral. We found biochemical complementarity between genomes of S. kawagutii and the anthozoan Acropora, indicative of host-symbiont coevolution, providing a resource for studying the molecular basis and evolution of coral symbiosis.

Autumn, the neglected season in climate change research

Abstract: Autumn remains a relatively neglected season in climate change research in temperate and arctic ecosystems. This neglect occurs despite the importance of autumn events, including leaf senescence, fruit ripening, bird and insect migration, and induction of hibernation and diapause. Changes in autumn phenology alter the reproductive capacity of individuals, exacerbate invasions, allow pathogen amplification and higher disease-transmission rates, reshuffle natural enemy‐prey dynamics, shift the ecological dynamics among interacting species, and affect the net productivity of ecosystems. We synthesize some of our existing understanding of autumn phenology and identify five areas ripe for future climate change research. We provide recommendations to address common pitfalls in autumnal research as well as to support the conservation and management of vulnerable ecosystems and taxa.

Health Consequences of Weight Stigma: Implications for Obesity Prevention and Treatment

Abstract: Despite decades of research documenting consistent stigma and discrimination against individuals with obesity, weight stigma is rarely considered in obesity prevention and treatment efforts. In recent years, evidence has examined weight stigmatization as a unique contributor to negative health outcomes and behaviors that can promote and exacerbate obesity. This review summarizes findings from published studies within the past 4 years examining the relationship between weight stigma and maladaptive eating behaviors (binge eating and increased food consumption), physical activity, weight status (weight gain and loss and development of obesity), and physiological stress responses. Research evaluating the effects of weight stigma present in obesity-related public health campaigns is also highlighted. Evidence collectively demonstrates negative implications of stigmatization for weight-related health correlates and behaviors and suggests that addressing weight stigma in obesity prevention and treatment is warranted. Key questions for future research to further delineate the health effects of weight stigmatization are summarized.

Muscle Strength: Clinical and Prognostic Value of Hand-grip Dynamometry

Abstract: Purpose of reviewGrip strength measured by dynamometry is well established as an indicator of muscle status, particularly among older adults. This review was undertaken to provide a synopsis of recent literature addressing the clinical and prognostic value of hand-grip dynamometry.Recent findingsNum

Diversity enhances carbon storage in tropical forests

Abstract: Aim Tropical forests store 25% of global carbon and harbour 96% of the world's tree species, but it is not clear whether this high biodiversity matters for carbon storage. Few studies have teased apart the relative importance of forest attributes and environmental drivers for ecosystem functioning, and no such study exists for the tropics. Location Neotropics. Methods We relate aboveground biomass (AGB) to forest attributes (diversity and structure) and environmental drivers (annual rainfall and soil fertility) using data from 144,000 trees, 2050 forest plots and 59 forest sites. The sites span the complete latitudinal and climatic gradients in the lowland Neotropics, with rainfall ranging from 750 to 4350 mm year−1. Relationships were analysed within forest sites at scales of 0.1 and 1 ha and across forest sites along large-scale environmental gradients. We used a structural equation model to test the hypothesis that species richness, forest structural attributes and environmental drivers have independent, positive effects on AGB. Results Across sites, AGB was most strongly driven by rainfall, followed by average tree stem diameter and rarefied species richness, which all had positive effects on AGB. Our indicator of soil fertility (cation exchange capacity) had a negligible effect on AGB, perhaps because we used a global soil database. Taxonomic forest attributes (i.e. species richness, rarefied richness and Shannon diversity) had the strongest relationships with AGB at small spatial scales, where an additional species can still make a difference in terms of niche complementarity, while structural forest attributes (i.e. tree density and tree size) had strong relationships with AGB at all spatial scales. Main conclusions Biodiversity has an independent, positive effect on AGB and ecosystem functioning, not only in relatively simple temperate systems but also in structurally complex hyperdiverse tropical forests. Biodiversity conservation should therefore be a key component of the UN Reducing Emissions from Deforestation and Degradation strategy.