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 <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<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<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.
he Pierre Auger Observatory, located on a vast, high plain in western\ud Argentina, is the world's largest cosmic ray observatory. The objectives\ud of the Observatory are to probe the origin and characteristics of cosmic\ud rays above 10(17) eV and to study the interactions of these, the most\ud energetic particles observed in nature. The Auger design features an\ud array of 1660 water Cherenkov particle detector stations spread over\ud 3000 km(2) overlooked by 24 air fluorescence telescopes. In addition,\ud three high elevation fluorescence telescopes overlook a 23.5 km(2),\ud 61-detector infilled array with 750 in spacing. The Observatory has been\ud in successful operation since completion in 2008 and has recorded data\ud from an exposure exceeding 40,000 km(2) sr yr. This paper describes the\ud design and performance of the detectors, related subsystems and\ud infrastructure that make up the Observatory
Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrated a correlation between the arrival directions of cosmic rays with energy above 6 x 10(19) electron volts and the positions of active galactic nuclei (AGN) lying within approximately 75 megaparsecs. We rejected the hypothesis of an isotropic distribution of these cosmic rays with at least a 99% confidence level from a prescribed a priori test. The correlation we observed is compatible with the hypothesis that the highest-energy particles originate from nearby extragalactic sources whose flux has not been substantially reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.
20 pages, 3 figures Submitted to Phys.Rev.Lett.International audienceThe surface detector array of the Pierre Auger Observatory is sensitive to Earth-skimming tau neutrinos that interact in Earth's crust. Tau leptons from ντ charged-current interactions can emerge and decay in the atmosphere to produce a nearly horizontal shower with a significant electromagnetic component. The data collected between 1 January 2004 and 31 August 2007 are used to place an upper limit on the diffuse flux of ντ at EeV energies. Assuming an Eν-2 differential energy spectrum the limit set at 90% C.L. is Eν2dNντ/dEν<1.3×10-7GeVcm-2s-1sr-1 in the energy range 2×1017e
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