Twenty-three unsolved problems in hydrology (UPH) – a community perspective

This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through on-line media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focussed on process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come

If the Worst Comes to the Worst. Dictator Giving When Recipient's Endowments are Risky

Donors may often not be sure whether a recipient really deserves their help. Does this uncertainty deter generosity? In an experiment we find that, to the contrary, under most specifications of uncertainty, dictators give more, compared with the donation the same dictator makes to a recipient they know to have the expected value of the endowment with certainty. They are particularly concerned about the possibility that a recipient leaves the lab with no payoff from the game

Dictator Games: A Meta Study

Over the last 25 years, more than a hundred dictator game experiments have been published. This meta study summarizes the evidence. Exploiting the fact that most experiments had to fix parameters they did not intend to test, the meta study explores a rich set of control variables for multivariate analysis. It shows that Tobit models (assuming that dictators would even want to take money) and hurdle models (assuming that the decision to give a positive amount is separate from the choice of amount, conditional on giving) outperform mere meta-regression and OLS

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

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

Epidemiology of respiratory syncytial virus in children younger than 5 years in England during the COVID-19 pandemic, measured by laboratory, clinical, and syndromic surveillance: a retrospective observational study

BackgroundSeasonal epidemics of respiratory syncytial virus (RSV) cause a clinically significant burden of disease among young children. Non-pharmaceutical interventions targeted at SARS-CoV-2 have affected the activity of other respiratory pathogens. We describe changes in the epidemiology of RSV among children younger than 5 years in England since 2020.MethodsSurveillance data on RSV infections, comprising laboratory-confirmed cases, proportion of positive tests, hospital admissions for RSV-attributable illness, and syndromic indicators for RSV-associated disease (emergency department attendances for acute bronchitis or bronchiolitis, non-emergency health advice telephone service [NHS 111] calls for cough, general practitioner [GP] in-hours consultations for respiratory tract infections, and GP out-of-hours contacts for acute bronchitis or bronchiolitis) were analysed from Dec 29, 2014 to March 13, 2022, for children younger than 5 years. Data were extracted from national laboratory, clinical, and syndromic surveillance systems. Time-series analyses using generalised linear models were used to estimate the effect of non-pharmaceutical interventions targeting SARS-CoV-2 on RSV indicators, with absolute and relative changes calculated by comparing observed and predicted values.FindingsRSV-associated activity was reduced for all RSV indicators during winter 2020-21 in England, with 10 280 (relative change -99·5% [95% prediction interval -100·0 to -99·1]) fewer laboratory-confirmed cases, 22·2 (-99·6%) percentage points lower test positivity, 92 530 (-80·8% [-80·9 to -80·8]) fewer hospital admissions, 96 672 (-73·7% [-73·7 to -73·7]) fewer NHS 111 calls, 2924 (-88·8% [-90·4 to -87·2]) fewer out-of-hours GP contacts, 91 304 (-89·9% [-90·0 to -89·9]) in-hours GP consultations, and 27 486 (-85·3% [-85·4 to -85·2]) fewer emergency department attendances for children younger than 5 years compared with predicted values based on winter seasons before the COVID-19 pandemic. An unprecedented summer surge of RSV activity occurred in 2021, including 11 255 (1258·3% [1178·3 to 1345·8]) extra laboratory-confirmed cases, 11·6 percentage points (527·3%) higher test positivity, 7604 (10·7% [10·7 to 10·8]) additional hospital admissions, 84 425 (124·8% [124·7 to 124·9]) more calls to NHS 111, 409 (39·0% [36·6 to 41·8]) more out-of-hours GP contacts, and 9789 (84·9% [84·5 to 85·4]) more emergency department attendances compared with the predicted values, although there were 21 805 (-34·1% [-34·1 to -34·0]) fewer in-hours GP consultations than expected. Most indicators were also lower than expected in winter 2021-22, although to a lesser extent than in winter 2020-21.InterpretationThe extraordinary absence of RSV during winter 2020-21 probably resulted in a cohort of young children without natural immunity to RSV, thereby raising the potential for increased RSV incidence, out-of-season activity, and health-service pressures when measures to restrict SARS-CoV-2 transmission were relaxed.FundingNone