289 research outputs found

    A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR)

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    Background: Granulocyte–macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19. Methods: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18–79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. Results: In Part 1 (n=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI −0.8–11.4%, p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2–33.1%, p=0.009) was observed in the predefined 70–79 years subgroup, but this was not confirmed in Part 2 (n=350 randomised) where the model-adjusted difference was 0.9% (95% CI −9.3–11.2%, p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CC chemokine ligand 17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. Conclusions: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile

    Identifying acne treatment uncertainties via a James Lind Alliance Priority Setting Partnership

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    Objectives: The Acne Priority Setting Partnership (PSP) was set up to identify and rank treatment uncertainties by bringing together people with acne, and professionals providing care within and beyond the National Health Service (NHS). Setting: The UK with international participation. Participants: Teenagers and adults with acne, parents, partners, nurses, clinicians, pharmacists, private practitioners. Methods: Treatment uncertainties were collected via separate online harvesting surveys, embedded within the PSP website, for patients and professionals. A wide variety of approaches were used to promote the surveys to stakeholder groups with a particular emphasis on teenagers and young adults. Survey submissions were collated using keywords and verified as uncertainties by appraising existing evidence. The 30 most popular themes were ranked via weighted scores from an online vote. At a priority setting workshop, patients and professionals discussed the 18 highest-scoring questions from the vote, and reached consensus on the top 10. Results: In the harvesting survey, 2310 people, including 652 professionals and 1456 patients (58% aged 24 y or younger), made submissions containing at least one research question. After checking for relevance and rephrasing, a total of 6255 questions were collated into themes. Valid votes ranking the 30 most common themes were obtained from 2807 participants. The top 10 uncertainties prioritised at the workshop were largely focused on management strategies, optimum use of common prescription medications and the role of nondrug based interventions. More female than male patients took part in the harvesting surveys and vote. A wider range of uncertainties were provided by patients compared to professionals. Conclusions: Engaging teenagers and young adults in priority setting is achievable using a variety of promotional methods. The top 10 uncertainties reveal an extensive knowledge gap about widely used interventions and the relative merits of drug versus non-drug based treatments in acne management

    The role of implicit affective responses and trait self-control in ego resource management

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    Exertion of self-control requires reliance on ego resources. Impaired performance typically results once those resources have been depleted by previous use. Yet the mechanism behind the depletion processes is little understood. Beliefs, motivation, and physiological changes have been implicated, yet the source behind these remains unknown. We propose that implicit may form the fundamental building blocks that these processes rely upon to operate. Implicit affective responses to energy may trigger management of ego resources after depletion. Findings suggest that inhibitory trait self-control may interact with the depletion effect, indicating the importance of taking individual differences in chronic availability of ego-resources into account. After depletion, individuals high in trait self-control may be less motivated to conserve remaining resources than those low in self-control. This mechanism may also help explain the conservation of resources observed when expecting multiple tasks requiring self-control

    Salford postgraduate annual research conference (SPARC) 2012 proceedings

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    These proceedings bring together a selection of papers from the 2012 Salford Postgraduate Annual Research Conference (SPARC). They reflect the breadth and diversity of research interests showcased at the conference, at which over 130 researchers from Salford, the North West and other UK universities presented their work. 21 papers are collated here from the humanities, arts, social sciences, health, engineering, environment and life sciences, built environment and business

    Removal of steroid estrogens in carbonaceous and nitrifying activated sludge processes

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    This is the post-print version of the final paper published in Chemosphere. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2010 Elsevier B.V.A carbonaceous (heterotrophic) activated sludge process (ASP), nitrifying ASP and a nitrifying/denitrifying ASP have been studied to examine the role of process type in steroid estrogen removal. Biodegradation efficiencies for total steroid estrogens (ΣEST) of 80 and 91% were recorded for the nitrifying/denitrifying ASP and nitrifying ASP respectively. Total estrogen biodegradation (ΣEST) was only 51% at the carbonaceous ASP, however, the extent of biodegradation in the absence of nitrification clearly indicates the important role of heterotrophs in steroid estrogen removal. The low removal efficiency did not correlate with biomass activity for which the ASPcarbonaceous recorded 80 μg kg−1 biomass d−1 compared to 61 and 15 μg kg−1 biomass d−1 at the ASPnitrifying and ASPnitrifying/denitrifying respectively. This finding was explained by a moderate correlation (r2 = 0.55) between total estrogen loading (ΣEST mg m−3 d−1) and biomass activity (μg ΣEST degraded kg−1 d−1) and has established the impact of loading on steroid estrogen removal at full-scale. At higher solids retention time (SRT), steroid estrogen biodegradation of >80% was observed, as has previously been reported. It is postulated that hydraulic retention time (HRT) is as important as SRT as this governs both reaction time and loading. This observation is based on the high specific estrogen activity determined at the ASPcarbonaceous plant, the significance of estrogen loading and the positive linear correlation between SRT and HRT.Public Utilities Board of Singapore, Anglian Water Ltd., Severn Trent Water Ltd., Thames Water Utilities Ltd., United Utilities Plc., and Yorkshire Water Services Ltd

    Monocarboxylate transporter expression remains unchanged during the development of diabetic retinal neuropathy in the rat

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    PURPOSE. To determine the effect of diabetes on monocarboxylate transporter (MCT) expression in the rat retina
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