Discriminating between the origins of remotely sensed circular structures:carbonate mounds, diapirs or periclinal folds? Purbeck Limestone Group, Weymouth Bay, UK

Many sedimentary rock successions contain plan-view circular structures, such as impacts, diapirs and carbonate build-ups. When remotely sensed, it can be difficult to discriminate between their formation mechanisms. Here we examine this problem by assessing the origins of circular structures imaged in high-resolution multibeam bathymetric data from Weymouth Bay, UK. The imagery shows 30–150 m across, concave-down structures within the upper Purbeck Limestone Group on the southern limb of the Purbeck Anticline. Similar structures have not been identified in the extensive outcrops around the bay. The morphology and geological setting of the structures are consistent with three different interpretations: carbonate mounds, periclinal folds and evaporite diapirs. However, none of these structures has been previously recorded in the upper Purbeck Limestone Group outcrops of this internationally renowned geological region. We apply a scoring system to 25 features of the circular structures to discriminate between these three alternative interpretations. This analysis indicates that evaporite diapirs are the least likely and carbonate mounds the most likely origin of the structures. The presence of carbonate mounds revises the upper Purbeck palaeofacies distribution in its type area and provides an analogue for the exploration for hydrocarbon reservoirs in lacustrine mounds

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

Water futures: The evolution of water scenarios

Until recently water resources management was done by extrapolating trends of individual indicators. Forty years ago studies showed social and economic factors interact, affecting global resources. Shell used scenarios to better understand the future of oil resources. Shiklomanov in 1998 completed a global study of future water resources use and availability. On the basis of his work and a scenario development process similar to Shell's, in 2000 the World Water Council published water resource management scenarios. In 2006 the UN World Water Development Report showed these scenarios were optimistic about the adoption of policies to improve water resources management. Decision-makers other than water managers were responsible for making and implementing such policies. Accelerating change and discontinuity in driving forces increase the uncertainty facing decision-makers. The Water Futures and Solutions Initiative now underway will advance this rapidly moving field using applied integrated systems analysis

Making Water Everyone's Business

Vision Statement and Key Messages Vision statement Actions needed Responsibility for implementation The Use of Water Today The world's water resources Main uses of water for human purposes Threats to nature-and to people Key water management issues Water Futures Turning points in water futures Scenarios and models Projected water use and water stress in 2025 Expanding irrigated agriculture Increasing water productivity Developing biotechnology for agriculture Increasing storage Reforming water resource management institutions Valuing ecosystem functions Increasing cooperation in international basins Supporting innovation World Water Vision Our Vision of Water and Life in 2025 People come first... but we cannot live without the rest of nature How we achieved our Vision Investing for the Water Future Closing the resource gap Mobilising new financial resources Launching a movementKWP-collectio

World Water Vision: Making Water Everybody's Business

Vision of the World Water Council on the use of water in the next centrury.KWP-collectio

Water and the Future of Humanity: Revisiting Water Security

This unique, engaging, and highly authoritative volume enlightens readers on changes needed in the way society accesses, provides, and uses water. It further shines a light on changes needed in the way we use food, energy, and other goods and services in relation to water, and offers projections and recommendations, up to 2050, that apply to water access challenges facing the poor and the common misuse of water in industry, agriculture, and municipalities. Written by an unparalleled slate of experts convened by the Calouste Gulbenkian Foundation, the book takes on one of the most critical issues on the planet today. In a frank yet optimistic assessment of major developmental challenges, but also opportunities, facing future generations, the author elucidates linkages between water and a range of other drivers from various disciplinary and stakeholder perspectives. Ultimately portraying the belief that Humanity can harness its visionary abilities, technologies, and economic resources for increased wellbeing and sound stewardship of resources, the book presents an optimistic statement stressing actions scientists, policy makers, and consumers can and must take to meet the water management challenges of a warming planet anticipating nine billion inhabitants by 2050