316 research outputs found

    An Observational Diagnostic for Ultraluminous X-Ray Sources

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    We consider observational tests for the nature of Ultraluminous X-ray sources (ULXs). These must distinguish between thermal-timescale mass transfer on to stellar-mass black holes leading to anisotropic X-ray emission, and accretion on to intermediate-mass black holes. We suggest that long-term transient behavior via the thermal-viscous disk instability could discriminate between these two possibilities for ULXs in regions of young stellar populations. Thermal-timescale mass transfer generally produces stable disks and persistent X-ray emission. In contrast, mass transfer from massive stars to black holes produces unstable disks and thus transient behavior, provided that the black hole mass exceeds some minimum value. This minimum mass depends primarily on the donor mass and evolutionary state. We show that it exceeds 50 solar masses for a large fraction (greater than 90%) of the mass-transfer lifetime for the most likely donors in young clusters. Thus if long-term monitoring reveals a large transient fraction among ULXs in a young stellar population, these systems would be good candidates for intermediate-mass black holes in a statistical sense; information about the donor star is needed to make this identification secure in any individual case. A transient ULX population would imply a much larger population of quiescent systems of the same type.Comment: 4 pages, 2 figure, ApJ Letters, in press (correct figure 2 included in this version

    The incidence of arthropathy adverse events in efalizumab-treated patients is low and similar to placebo and does not increase with long-term treatment: pooled analysis of data from Phase III clinical trials of efalizumab

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    A large-scale, pooled analysis of safety data from five Phase III clinical trials (including open-label extensions of two of these studies) and two Phase III open-label clinical trials of efalizumab was conducted to explore whether arthropathy adverse events (AEs) were associated with efalizumab treatment in patients with moderate-to-severe chronic plaque psoriasis. Data from patients who received subcutaneous injections of efalizumab or placebo were stratified for analysis into phases according to the nature and duration of treatment. These included: the ‘first treatment’ phase (0–12-week data from patients who received either efalizumab, 1 mg/kg once weekly, or placebo in the five placebo-controlled studies); the ‘extended treatment’ phase (13–24-week data from seven trials for all efalizumab-treated patients); and the ‘long-term treatment’ phase (data from efalizumab-treated patients who received treatment for up to 36 months in two long-term trials). Descriptive statistics were performed and the incidence of arthropathy AEs per patient-year was calculated using 95% confidence intervals (CIs). During the first treatment phase, a similar proportion of patients had an arthropathy AE in the efalizumab group (3.3%; 58/1740 patients) compared with the placebo group (3.5%; 34/979 patients); the incidence of arthropathy AEs per patient-year was 0.15 in the efalizumab group (95% CI 0.11–0.19) and 0.16 in the placebo group (95% CI 0.11–0.22). Analysis of first treatment phase data from one study (n = 793) showed that the incidence of psoriatic arthropathy per patient-year was lower in efalizumab-treated patients (0.10; 95% CI 0.05–0.18) than in those given placebo (0.17; 95% CI 0.08–0.30). During the extended treatment phase, the incidence of arthropathy remained low (0.17; 95% CI 0.14–0.22). Data from two long-term studies showed that there was no increase in the incidence of arthropathy AEs over time in patients treated with efalizumab for up to 36 months. Patients who had an arthropathy AE during treatment with efalizumab appeared to be more likely to have a history of arthropathy prior to treatment. Efalizumab does not appear to increase the risk of arthropathy AEs compared with placebo

    Stakeholder engagement in the city branding process

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    This paper explores perceptions of stakeholder engagement in the city branding process from the perspective of two post-industrial cities: Sheffield, UK and Essen, Germany. This qualitative research utilises a multi case study approach, which allowed for semi-structure interviews and semiotics to be used. Preliminary findings highlight that there are four stakeholder ‘levels’. Each of these stakeholder groupings is involved in the city branding process to some extend. Findings suggest that the degree of involvement strongly depends on the primary stakeholders, who are seen as key decision-makers in the branding process. These primary stakeholders select other stakeholders that ‘can’ be involved in the branding process. Although this may be beneficial it is vital to provide more opportunities and incorporate stakeholders that are willing to participate in the branding process. Alienating stakeholders may also lead to losing parts of an identity that is based on heritage. The focus is on two cities with a highly industrialised background, thus findings may not be applicable to cities without this heritage. The paper looks at both stakeholder engagement and city branding, thereby proposing four layers of stakeholder involvement in the city branding process

    To be understood: Transitioning to adult life for people with Autism Spectrum Disorder

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    Introduction: The purpose of this study was to explore the viewpoints of parents of young people with Autism Spectrum Disorder (ASD) in relation to their child's transition to adulthood. Methods: Data were collected during four structured focus groups with 19 parents of young people with ASD with average to high intellectual capacities. Condensed meaning units were identified and checked during focus groups, and were subsequently linked to the International Classification of Functioning, Disability and Health (ICF). Results: Three major themes emerged: to be understood, to understand the world and to succeed. The ICF domains of activity and participation and environmental factors emerged as having the greatest potential to influence transition outcomes. Conclusions: Policies and services should focus on strengths to maximise participation in higher education, employment and independent living amongst young people with ASD. Interventions targeting environmental factors could be effective in improving participation in adult life. Person-centred and individualised approaches could further complement this approach supporting the transition to adulthood for people with ASD, ultimately improving outcomes in adulthood

    Fibroblast growth factor-1 (FGF-1) promotes adipogenesis by downregulation of carboxypeptidase A4 (CPA4) – a negative regulator of adipogenesis implicated in the modulation of local and systemic insulin sensitivity

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    Fibroblast growth factor-1 (FGF-1) promotes differentiation of human preadipocytes into mature adipocytes via modulation of a BMP and Activin Membrane-Bound Inhibitor (BAMBI)/Peroxisome proliferator-activated receptor (PPAR?)-dependent network. Here, we combined transcriptomic and functional investigations to identify novel downstream effectors aligned with complementary analyses of gene expression in human adipose tissue to explore relationships with insulin sensitivity. RNA-Seq and qRT-PCR analysis revealed significant down-regulation of carboxypeptidase A4 (CPA4) following FGF-1 treatment or induction of differentiation of human preadipocytes in a BAMBI/PPAR?-independent manner. siRNA-mediated knockdown of CPA4 resulted in enhanced differentiation of human preadipocytes. Furthermore, expression of CPA4 in subcutaneous adipose tissue correlated negatively with indices of local and systemic (liver and muscle) insulin sensitivity. These results identify CPA4 as a negative regulator of adipogenesis that is down-regulated by FGF-1 and a putative deleterious modulator of local and systemic insulin sensitivity. Further investigations are required to define the molecular mechanism(s) involved and potential therapeutic opportunities

    The Pioneer Anomaly

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    Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit
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