27 research outputs found

    Efficacy and safety of ciclosporin versus methotrexate in the treatment of severe atopic dermatitis in children and young people (TREAT): a multicentre parallel group assessor-blinded clinical trial

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    Background Conventional systemic drugs are used to treat children and young people (CYP) with severe atopic dermatitis (AD) worldwide, but no robust randomized controlled trial (RCT) evidence exists regarding their efficacy and safety in this population. While novel therapies have expanded therapeutic options, their high cost means traditional agents remain important, especially in lower-resource settings. Objectives To compare the safety and efficacy of ciclosporin (CyA) with methotrexate (MTX) in CYP with severe AD in the TREatment of severe Atopic Eczema Trial (TREAT) trial. Methods We conducted a parallel group assessor-blinded RCT in 13 UK and Irish centres. Eligible participants aged 2–16 years and unresponsive to potent topical treatment were randomized to either oral CyA (4 mg kg–1 daily) or MTX (0.4 mg kg–1 weekly) for 36 weeks and followed-up for 24 weeks. Co-primary outcomes were change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare (relapse) after treatment cessation. Secondary outcomes included change in quality of life (QoL) from baseline to 60 weeks; number of participant-reported flares following treatment cessation; proportion of participants achieving ≥ 50% improvement in Eczema Area and Severity Index (EASI 50) and ≥ 75% improvement in EASI (EASI 75); and stratification of outcomes by filaggrin status. Results In total, 103 participants were randomized (May 2016–February 2019): 52 to CyA and 51 to MTX. CyA showed greater improvement in disease severity by 12 weeks [mean difference in o-SCORAD –5.69, 97.5% confidence interval (CI) –10.81 to –0.57 (P = 0.01)]. More participants achieved ≥ 50% improvement in o-SCORAD (o-SCORAD 50) at 12 weeks in the CyA arm vs. the MTX arm [odds ratio (OR) 2.60, 95% CI 1.23–5.49; P = 0.01]. By 60 weeks MTX was superior (OR 0.33, 95% CI 0.13–0.85; P = 0.02), a trend also seen for ≥ 75% improvement in o-SCORAD (o-SCORAD 75), EASI 50 and EASI 75. Participant-reported flares post-treatment were higher in the CyA arm (OR 3.22, 95% CI 0.42–6.01; P = 0.02). QoL improved with both treatments and was sustained after treatment cessation. Filaggrin status did not affect outcomes. The frequency of adverse events (AEs) was comparable between both treatments. Five (10%) participants on CyA and seven (14%) on MTX experienced a serious AE. Conclusions Both CyA and MTX proved effective in CYP with severe AD over 36 weeks. Participants who received CyA showed a more rapid response to treatment, while MTX induced more sustained disease control after discontinuation

    The STAR experiment at the relativistic heavy ion collider

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    Upper Confidence Trees with Short Term Partial Information

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    International audienceWe show some mathematical links between partially observable (PO) games in which information is regu larly revealed, and simultaneous actions games. Using this, we study the extension of Monte-Carlo Tr ee Search algorithms to PO games and to games with simultaneous actions. We apply the results to Urb an Rivals, a free PO internet card game with more than 10 millions of registered users

    Fine-scale habitat preference of green sturgeon (Acipenser medirostris) within three spawning locations in the Sacramento River, California

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    Vast sections of the Sacramento River have been listed as critical habitat by the National Marine Fisheries Service for green sturgeon spawning (Acipenser medirostris), yet spawning is known to occur at only a few specific locations. This study reveals the range of physical habitat variables selected by adult green sturgeon during their spawning period. We integrated fine-scale fish positions, physical habitat characteristics, discharge, bathymetry, and simulated velocity and depth using a 2-dimensional hydraulic model (FaSTMECH). The objective was to create habitat suitability curves for depth, velocity, and substrate type within three known spawning locations over two years. An overall cumulative habitat suitability score was calculated that averaged the depth, velocity, and substrate scores over all fish, sites, and years. A weighted usable area (WUA) index was calculated throughout the sampling periods for each of the three sites. Cumulative results indicate that the microhabitat characteristics most preferred by green sturgeon in these three spawning locations were velocities between 1.0-1.1 m/s, depths of 8-9 m, and gravel and sand substrate. This study provides guidance for those who may in the future want to increase spawning habitat for green sturgeon within the Sacramento River.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
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