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.

Despite increasing attention to the human dimension of conservation projects, a rigorous, systematic methodology for planning for ecosystem services has not been developed. This is in part because flows of ecosystem services remain poorly characterized at local-to-regional scales, and their protection has not generally been made a priority. We used a spatially explicit conservation planning framework to explore the trade-offs and opportunities for aligning conservation goals for biodiversity with six ecosystem services (carbon storage, flood control, forage production, outdoor recreation, crop pollination, and water provision) in the Central Coast ecoregion of California, United States. We found weak positive and some weak negative associations between the priority areas for biodiversity conservation and the flows of the six ecosystem services across the ecoregion. Excluding the two agriculture-focused services—crop pollination and forage production—eliminates all negative correlations. We compared the degree to which four contrasting conservation network designs protect biodiversity and the flow of the six services. We found that biodiversity conservation protects substantial collateral flows of services. Targeting ecosystem services directly can meet the multiple ecosystem services and biodiversity goals more efficiently but cannot substitute for targeted biodiversity protection (biodiversity losses of 44% relative to targeting biodiversity alone). Strategically targeting only biodiversity plus the four positively associated services offers much promise (relative biodiversity losses of 7%). Here we present an initial analytical framework for integrating biodiversity and ecosystem services in conservation planning and illustrate its application. We found that although there are important potential trade-offs between conservation for biodiversity and for ecosystem services, a systematic planning framework offers scope for identifying valuable synergies.

Simulations are run until the year 3000 A.D. and extend substantially farther into the future than conceptually similar simulations with atmosphere-ocean general circulation models (AOGCMs) coupled to carbon cycle models. In this paper the following are investigated: 1) the climate change commitment in response to stabilized greenhouse gases and stabilized total radiative forcing, 2) the climate change commitment in response to earlier CO 2 emissions, and 3) emission trajectories for profiles leading to the stabilization of atmospheric CO 2 and their uncertainties due to carbon cycle processes. Results over the twenty-first century compare reasonably well with results from AOGCMs, and the suite of EMICs proves well suited to complement more complex models. Substantial climate change commitments for sea level rise and global mean surface temperature increase after a stabilization of atmospheric greenhouse gases and radiative forcing in the year 2100 are identified. The additional warming by the year 3000 is 0.6-1.6 K for the low-CO 2 IPCC Special Report on Emissions Scenarios (SRES) B1 scenario and 1.3-2.2 K for the high-CO 2 SRES A2 scenario. Correspondingly, the post-2100 thermal expansion commitment is 0.3-1.1 m for SRES B1 and 0.5-2.2 m for SRES A2. Sea level continues to rise due to thermal expansion for several centuries after CO 2 stabilization. In contrast, surface temperature changes slow down after a century. The meridional overturning circulation is weakened in all EMICs, but recovers to nearly initial values in all but one of the models after centuries for the scenarios considered. Emissions during the twenty-first century continue to impact atmospheric CO 2 and climate even at year 3000. All models find that most of the anthropogenic carbon emissions are eventually taken up by the ocean (49%-62%) in year 3000, and that a substantial fraction (15%-28%) is still airborne even 900 yr after carbon emissions have ceased. Future stabilization of atmospheric CO 2 and climate change requires a substantial reduction of CO 2 emissions below present levels in all EMICs. This reduction needs to be substantially larger if carbon cycle-climate feedbacks are accounted for or if terrestrial CO 2 fertilization is not operating. Large differences among EMICs are identified in both the response to increasing atmospheric CO 2 and the response to climate change. This highlights the need for improved representations of carbon cycle processes in these models apart from the sensitivity to climate change. Sensitivity simulations with one single EMIC indicate that both carbon cycle and climate sensitivity related uncertainties on projected allowable emissions are substantial.n Current affiliation: IBP, ETH Zürich, Zürich, Switzerland.

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