A New Neutrino Cross Section Database

We describe a new web based data resource being developed to provide access to accurate and validated cross sections of low energy neutrino and antineutrino interactions. The proposed content of this database are outlined which cover total and differential cross from inclusive, quasi-elastic and exclusive pion production processes from charged and neutral current interactions. Efforts to obtain these data, which come mainly from old bubble chamber experiments, are described as well as the implementation of an embryonic web site to make the resource generally accessible.Comment: 6 pages, 3 figures, To appear in the proceedings of the 3rd International Workshop on Neutrino Nucleus Interactions in the few GeV region (NuInt04), Gran Sasso, Assergi, Italy, 17-21 Mar 200

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

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

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

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. 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. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Hydrothermal plume - particle fluxes at 13N on the East Pacific Rise

We have investigated the geochemical flux to sediment traps deployed close to the Totem vent site, 13°N EPR. An important emphasis has been to investigate what proportion of this settling flux derives from direct co-precipitation of vent-fluid material as polymetallic sulphides and what proportion is in the form of Fe oxyhydroxide material which not only co-precipitates vent-fluid metals but can also scavenge dissolved material from seawater. Mass fluxes and major element compositions (Fe, S, Al, Mn, CaCO3 and Corg) for our near vent samples compare well with results from previously reported Pacific hydrothermal sediment trap studies, both at this site and on the Endeavour Ridge. Our samples record large fluxes of Cu, Zn and Pb, as well as V and P, all of which are in excess over typical open-ocean trap values. If P and V are transported to the traps as sinking Fe-oxyhydroxide material from the neutrally buoyant plume, we calculate that 10–20% of the Fe entering the near vent traps occurs as oxidised material with the remaining 80–90% being supplied by polymetallic sulphides. Shale-normalised REE distribution patterns for near-vent trap samples are similar to those for local vent fluids and sulphidic sediments. Detailed mass balance calculations, however, reveal evidence for additional input from hydrothermal Fe-oxyhydroxide material with a scavenged REE composition that is less "evolved" than that reported for local neutrally buoyant plume particles. U fluxes into the near vent traps are high and consistent with uptake by sulphides. 210Pb fluxes are also high and appear dominated by co-precipitation direct from vent-fluids as Pb-sulphides. In contrast, Fe-oxyhydroxide scavenging from seawater can account for the entire 230Th and 232Th fluxes reported. If the scavenging processes identified here were similarly active in neutrally buoyant plumes, we would predict hydrothermal scavenging to impact ocean biogeochemical cycles significantly, e.g. causing removal of ca. 10% of the dissolved 230Th production from the deep water column, out to a distance of ca. 10–100 km off-axis, along the entire 60,000 km global ridge-crest

Exploring the emergence of participatory plant breeding in countries of the Global North - A review

Participatory plant breeding (PPB), commonly applied in the Global South to address the needs of underserved farmers, refers to the active collaboration between researchers, farmers and other actors throughout the breeding process. In spite of significant public and private investments in crop variety improvement in the Global North, PPB is increasingly utilized as an approach to address cropping system needs. The current study conducted a state-of-the-art review, including a comprehensive inventory of projects and five case studies, to explore the emergence of PPB in the Global North and inform future PPB efforts. Case studies included maize (Zea mays), tomato (Solanum lycopersicum), Brassica crops (Brassica oleracea), wheat (Triticum aestivum) and potato (Solanum tuberosum). The review identified 47 projects across the United States, Canada and Europe including 22 crop species representing diverse crop biology. Improved adaptation to organic farming systems and addressing principles and values of organic agriculture emerged as consistent themes. While projects presented evidence that PPB has expanded crop diversity and farmer's access to improved varieties, obstacles to PPB also emerged including challenges in sustained funding as well as addressing regulatory barriers to the commercial distribution of PPB varieties. Agronomic improvements were only one lens motivating PPB, with many projects identifying goals of conservation of crop genetic diversity, farmers' seed sovereignty and avoidance of certain breeding techniques. The authors conclude that a multidisciplinary approach is needed to fully understand the social, political and agroecological influences driving the emergence of projects in the Global North and factors impacting success