224 research outputs found

    A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19:Accord-2

    Get PDF
    BACKGROUND: Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95).METHODS: ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay.RESULTS: Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels.CONCLUSIONS: Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.</p

    Abundance, predation, and habitat associations of lemming winter nests in northern Sweden

    Get PDF
    Spatially synchronous fluctuations of animal populations have profound ecological consequences, especially in northern latitudes. Spatially coupled fluctuations are often seen in small rodent populations, albeit with local and regional variations. While both resource limitation and predation influence rodent dynamics, their relative importance for generating spatial variation is less clear, particularly during winter. In this study, we quantify spatial variation in winter abundance of the Norwegian lemming (Lemmus lemmus) across three ecologically connected mountain areas in northern Sweden and evaluate whether the relative strength of bottom-up and top-down regulation influences such variation. Our data included observations of predated and nonpredated winter nests as well as environmental characteristics of nest locations and nest predation. While the direction of annual changes in lemming nest abundance was perfectly synchronized among the three areas, there were differences in nest abundance, potentially caused by contrasting amplitudes of temporal fluctuations in lemming winter populations. Mustelid predation was positively associated with decreasing lemming populations but did not differ in occurrence among the three areas. Lemming nests were predominantly observed in meadows, whereas areas prone to flooding and close to the tree line were underrepresented. Mustelid predation was most common close to the tree line, but not associated with geomorphological characteristics related to snow depth. We suggest that the observed differences in lemming winter abundances were caused by variations in the relative strength of bottom-up and top-down regulation in the three mountain areas. We encourage further studies evaluating how the relative strength of different processes influence local population regulation, and how such processes influence spatial variation in animal population dynamics at different spatial scales.This study was funded by the Oscar and Lili Lamm Memorial Foundation (FO2018-0022), the Wildlife Management Fund (802-0199-18) by the Swedish Environmental Protection Agency, WWF Sweden, Fjällräven International AB, and EU Interreg Felles Nord II (20203530)

    Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

    No full text
    Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata 35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.gov; Unique identifier: NCT01663402.URL: https://www

    A study of mobile app use for teaching and research in higher education

    Get PDF
    The exponential growth in the use of digital technologies and the availability of mobile software applications (apps) has been well documented over the past decade. Literature on the integration of mobile technology into higher education reveals an increasing focus on how mobile devices are used within the classroom environment, both physical and online, rather than on how mobile applications may be used for either teaching or the research process. Our study surveyed staff and higher degree research students at a New Zealand university using an online questionnaire to gain insight into the use of mobile apps for tertiary teaching and research, seeking information, particularly on which apps were used for which tasks and what obstacles hindered their use. The online survey used 29 questions and ran in 2016/2017. 269 participants completed the survey, nearly 20% of the potential sample. We found that mobile apps were used by academics and students for both teaching and research, primarily in the form of document and data storage and exchange, and communication. Very little app use was recorded for in-class activities (teaching) or in-field activities (research). Apps use resulted from personal motivation rather than institutional planning. Both students and academics reported that institutional support and flexibility would likely provide motivation and lead to increased app use for both research and teaching

    Neutralisation of SARS-CoV-2 by anatomical embalming solutions

    No full text
    Teaching and learning anatomy by using human cadaveric specimens has been a foundation of medical and biomedical teaching for hundreds of years. Therefore, the majority of institutions that teach topographical anatomy rely on body donation programmes to provide specimens for both undergraduate and postgraduate teaching of gross anatomy. The COVID-19 pandemic has posed an unprecedented challenge to anatomy teaching because of the suspension of donor acceptance at most institutions. This was largely due to concerns about the potential transmissibility of the SARS-CoV-2 virus and the absence of data about the ability of embalming solutions to neutralise the virus. Twenty embalming solutions commonly used in institutions in the United Kingdom and Ireland were tested for their ability to neutralise SARS-CoV-2, using an established cytotoxicity assay. All embalming solutions tested neutralised SARS-CoV-2, with the majority of solutions being effective at high-working dilutions. These results suggest that successful embalming with the tested solutions can neutralise the SARS-CoV-2 virus, thereby facilitating the safe resumption of body donation programmes and cadaveric anatomy teaching. </p

    Meteorological data rescue: citizen science lessons learned from Southern Weather Discovery

    Get PDF
    Daily weather reconstructions (called "reanalyses") can help improve our understanding of meteorology and long-term climate changes. Adding undigitized historical weather observations to the datasets that underpin reanalyses is desirable; however, time requirements to capture those data from a range of archives is usually limited. Southern Weather Discovery is a citizen science data rescue project that recovered tabulated handwritten meteorological observations from ship log books and land-based stations spanning New Zealand, the Southern Ocean, and Antarctica. We describe the Zooniverse-hosted Southern Weather Discovery campaign, highlight promotion tactics, and replicate keying levels needed to obtain 100% complete transcribed datasets with minimal type 1 and type 2 transcription errors. Rescued weather observations can augment optical character recognition (OCR) text recognition libraries. Closer links between citizen science data rescue and OCR-based scientific data capture will accelerate weather reconstruction improvements, which can be harnessed to mitigate impacts on communities and infrastructure from weather extremes

    Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

    Get PDF
    Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

    Developing a programme theory for a transdisciplinary research collaboration: Complex Urban Systems for Sustainability and Health

    Get PDF
    Background: Environmental improvement is a priority for urban sustainability and health and achieving it requires transformative change in cities. An approach to achieving such change is to bring together researchers, decision-makers, and public groups in the creation of research and use of scientific evidence. Methods: This article describes the development of a programme theory for Complex Urban Systems for Sustainability and Health (CUSSH), a four-year Wellcome-funded research collaboration which aims to improve capacity to guide transformational health and environmental changes in cities. Results: Drawing on ideas about complex systems, programme evaluation, and transdisciplinary learning, we describe how the programme is understood to “work” in terms of its anticipated processes and resulting changes. The programme theory describes a chain of outputs that ultimately leads to improvement in city sustainability and health (described in an ‘action model’), and the kinds of changes that we expect CUSSH should lead to in people, processes, policies, practices, and research (described in a ‘change model’). Conclusions: Our paper adds to a growing body of research on the process of developing a comprehensive understanding of a transdisciplinary, multiagency, multi-context programme. The programme theory was developed collaboratively over two years. It involved a participatory process to ensure that a broad range of perspectives were included, to contribute to shared understanding across a multidisciplinary team. Examining our approach allowed an appreciation of the benefits and challenges of developing a programme theory for a complex, transdisciplinary research collaboration. Benefits included the development of teamworking and shared understanding and the use of programme theory in guiding evaluation. Challenges included changing membership within a large group, reaching agreement on what the theory would be ‘about’, and the inherent unpredictability of complex initiatives
    corecore