570 research outputs found

    Ovarian and cervical cancer awareness: development of two validated measurement tools.

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    The aim of the study was to develop and validate measures of awareness of symptoms and risk factors for ovarian and cervical cancer (Ovarian and Cervical Cancer Awareness Measures)

    A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis.

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    Background: Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. Objective: The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. Methods: This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1-4 hours on day 1 and 450-600 mg over 1-3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. Results: In all cohorts (N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1-2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions (p = 0.003) and a 10.6% decrease in T2 lesion volume (p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). Conclusion: Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses

    Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

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    Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

    'Let's make lots of money': the determinants of performance in the recorded music sector

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    This research analyzes the performance of 467 record labels in eight European countries over a period of 13 years (2003-2015). The main goal is to explain a relative measure of profitability in terms of observed variables, although the nature of the dataset also allows us to include non-observed firm and country effects. To this end alternative models are estimated and three main research questions are tested, namely: (1) the effect of the dual structure of the recorded music market, in which a competitive segment and an oligopoly coexist; (2) the extent and source of the volatility of profits in record labels; and (3) the nonlinear impact of size on performance

    Socioeconomic position and overweight among adolescents: data from birth cohort studies in Brazil and the UK

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    <p>Abstract</p> <p>Background</p> <p>Developed and developing countries are facing rapid increases in overweight and obesity among children and adolescents. The patterns of overweight/obesity differ by age, sex, rural or urban residence and socioeconomic position (SEP) and vary between and within countries.</p> <p>Methods</p> <p>We investigated patterns of SEP – overweight status association among adolescents from the UK (ALSPAC) and Brazil (the 1982 and 1993 Pelotas birth cohort studies).</p> <p>All analyses were performed separately for males and females. Logistic regression analysis was used to examine the relationships between overweight status and two SEP indicators – family income and maternal education.</p> <p>Results</p> <p>A strong positive association was observed in 11-year-old boys from the 1993 Pelotas cohort, with higher prevalence of overweight among the least poor and among those whose mothers had more years of schooling (<it>x</it><sup>2 </sup>for linear trend p < 0.001). In ALSPAC study higher prevalence of overweight was seen among boys whose mothers had lower educational achievement (<it>x</it><sup>2 </sup>for linear trend p = 0.006). Among 11 year-old girls from 1993 Pelotas cohort study there was a positive association (higher prevalence of overweight in the higher socioeconomic and educational strata, <it>x</it><sup>2 </sup>for linear trend p < 0.001 and p = 0.01, respectively) while an inverse association was found in the ALSPAC study (<it>x</it><sup>2 </sup>for linear trend p < 0.001). Among males from the 1982 cohort study, overweight at 18 years of age showed a positive association with both SEP indicators while among females, the reverse association was found.</p> <p>Conclusion</p> <p>The results of this study demonstrate that the social patterning of overweight varies between and within populations over time. Specific approaches should be developed within populations in order to contain the obesity epidemic and reduce disparities.</p

    Sub-Telomeric core X and Y' Elements in S.cerevisiae Suppress Extreme Variations in Gene Silencing

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    Telomere Position Effect (TPE) is governed by strong repression signals emitted by telomeres via the Sir2/3/4 Histone Deacetylase complex. These signals are then relayed by weak proto-silencers residing in the subtelomeric core X and Y' elements. Subtelomeres also contain Sub-Telomeric Anti-silencing Regions (STARs). In this study we have prepared telomeres built of different combinations of core X, Y' and STARs and have analyzed them in strains lacking Histone-Acetyltransferase genes as well as in cdc6-1 and Δrif1 strains. We show that core X and Y' dramatically reduce both positive and negative variations in TPE, that are caused by these mutations. We also show that the deletion of Histone-Acetyltransferase genes reduce the silencing activity of an ACS proto-silencer, but also reduce the anti-silencing activity of a STAR. We postulate that core X and Y' act as epigenetic “cushioning” cis-elements

    Dynamical Boson Stars

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    The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called {\em geons}, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name {\em boson stars}. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in Relativity; major revision in 201
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