10 research outputs found

    Validation of Skeletal Muscle cis-Regulatory Module Predictions Reveals Nucleotide Composition Bias in Functional Enhancers

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    We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions

    ADHD and sleep quality: Longitudinal analyses from childhood to early adulthood in a twin cohort

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    Attention-deficit/hyperactivity disorder (ADHD) is associated with poor sleep quality, but there is more to learn about the longitudinal association and aetiology of this association. We investigated the following: (a) Is there an association between childhood ADHD and poor sleep quality in young adulthood? (b) Is this driven by the long-term effects of childhood ADHD or concurrent associations with ADHD in young adulthood? (c) To what extent do genetic and environmental influences explain the overlap between symptoms of ADHD and poor sleep quality? Participants were from the Environmental Risk Longitudinal Twin Study of 2,232 twin children born in the United Kingdom in 1994–1995. We ascertained ADHD diagnoses at ages 5, 7, 10, 12, and 18. We assessed sleep quality using the Pittsburgh Sleep Quality Index at age 18. We used regression models to examine longitudinal associations and bivariate twin modelling to test genetic and environmental influences. Children with ADHD had poorer sleep quality in young adulthood, but only if their ADHD persisted. Adults with ADHD had more sleep problems than those without ADHD, over and above psychiatric comorbidity and maternal insomnia. ADHD and sleep problems in young adulthood were associated because of genetic (55%) and nonshared environmental influences (45%). Should ADHD remit, children with ADHD do not appear to have an increased risk of later sleep problems. Good quality sleep is important for multiple areas of functioning, and a better understanding of why adults with ADHD have poorer sleep quality will further the goal of improving treatments

    An Exploration of Correct Voting in Recent U.S. Presidential Elections

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    Lau and Redlawsk (1997) proposed that the quality of voter decision making can be evaluated by measuring what they called correct voting—the extent to which people vote in accordance with their own values and priorities—but in so doing provided little guidance about what actually determines whether voters can make such high-quality decisions. This article develops a framework for analyzing the vote decision that views the quality of decision making as a joint function of individual characteristics and various higher-level campaign factors. We hypothesize that differences in cognitive capacity, political motivation, the availability of political heuristics, and macrolevel factors that affect the difficulty of the choice confronting citizens, including the nature of the political information environment, should all affect the probability of a correct vote. We find significant support for seven proposed hypotheses across three levels of analysis, which places responsibility for incorrect votes on both the individual and our electoral system. Democracy works best when citizens are interestedin politics, able to place current events in properhistorical context, attentive to the actions of rep-resentatives in government, aware of institutional rules and requirements so that responsibility for government actions can be properly attributed, and engaged in the governing process to the extent they vote for the candi-dates they believe best represent their interests. This is

    2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement

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    Canada

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    Canada

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    Canada

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