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.

Campylobacter is a common cause of gastroenteritis in the United States. We conducted a population-based case-control study to determine risk factors for sporadic Campylobacter infection. During a 12-month study, we enrolled 1316 patients with culture-confirmed Campylobacter infections from 7 states, collecting demographic, clinical, and exposure data using a standardized questionnaire. We interviewed 1 matched control subject for each case patient. Thirteen percent of patients had traveled abroad. In multivariate analysis of persons who had not traveled, the largest population attributable fraction (PAF) of 24% was related to consumption of chicken prepared at a restaurant. The PAF for consumption of nonpoultry meat that was prepared at a restaurant was also large (21%); smaller proportions of illness were associated with other food and nonfood exposures. Efforts to reduce contamination of poultry with Campylobacter should benefit public health. Restaurants should improve food-handling practices, ensure adequate cooking of meat and poultry, and consider purchasing poultry that has been treated to reduce Campylobacter contamination.

While stigma associated with HIV infection is well recognised, there is limited information on the impact of HIV-related stigma between men who have sex with men and within communities of gay men. The consequences of HIV-related stigma can be personal and community-wide, including impacts on mood and emotional well-being, prevention, testing behaviour, and mental and general health. This review of the literature reports a growing division between HIV-positive and HIV-negative gay men, and a fragmentation of gay communities based along lines of perceived or actual HIV status. The literature includes multiple references to HIV stigma and discrimination between gay men, men who have sex with men, and among and between many gay communities. This HIV stigma takes diverse forms and can incorporate aspects of social exclusion, ageism, discrimination based on physical appearance and health status, rejection and violence. By compiling the available information on this understudied form of HIV-related discrimination, we hope to better understand and target research and countermeasures aimed at reducing its impact at multiple levels.

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Astrovirus infection in a variety of species results in an age-dependent diarrhea; however, the means by which astroviruses cause diarrhea remain unknown. Studies of astrovirus-infected humans and turkeys have demonstrated few histological changes and little inflammation during infection, suggesting that intestinal damage or an overzealous immune response is not the primary mediator of astrovirus diarrhea. An alternative contributor to diarrhea is increased intestinal barrier permeability. Here, we demonstrate that astrovirus increases barrier permeability in a Caco-2 cell culture model system following apical infection. Increased permeability correlated with disruption of the tight-junction protein occludin and decreased the number of actin stress fibers in the absence of cell death. Additionally, permeability was increased when monolayers were treated with UV-inactivated virus or purified recombinant human astrovirus serotype 1 capsid in the form of virus-like particles. Together, these results demonstrate that astrovirus-induced permeability occurs independently of viral replication and is modulated by the capsid protein, a property apparently unique to astroviruses. Based on these data, we propose that the capsid contributes to diarrhea in vivo.

Despite an increase in secondary intraventricular bleeding, DRIFT reduced severe cognitive disability in survivors and overall death or severe disability.

The approach of this study was to determine, theoretically, what impact current and future urban land use in the coastal city of Houston, Texas has on the space and time evolution of precipitation on a ‘typical’ summer day. Regional model simulations of a case study for 25 July 2001 were applied to investigate possible effects of urban land cover on precipitation development. Simulations in which Houston urban land cover was included resolved rain cells associated with the sea breeze front and a possible urban circulation on the northwest fringe of the city. Simulations without urban land cover did not capture the initiation and full intensity of the ‘hypothesized’ urban-induced rain cell. The response is given the terminology the ‘urban rainfall effect’ or URE. An urban growth model (UrbanSim) was used to project the urban land-cover growth of Houston, Texas from 1992 to 2025. A regional atmospheric-land surface model was then run with the 2025 urban land-cover scenario. Though we used a somewhat theoretical treatment, our results show the sensitivity of the atmosphere to urban land cover and illustrate how atmosphere — land interactions can affect cloud and precipitation processes. Two urban-induced features, convergence zones along the inner fringe of the city and an urban low-pressure perturbation, appear to be important factors that lead to enhanced rain clouds independently or in conjunction with the sea breeze. Simulations without the city (NOURBAN) produced less cumulative rainfall in the west-northwest Houston area than simulations with the city represented (URBAN). Future urban land-cover growth projected by UrbanSim (URBAN2025) led to a more expansive area of rainfall, owing to the extended urban boundary and increased secondary outflow activity. This suggests that the future urban land cover might lead to temporal and spatial precipitation variability in coastal urban microclimates. It was beyond the scope of the analysis to conduct an extensive sensitivity analysis of cause — effect relationships, though the experiments provide some clues as to why the rainfall evolution differs. This research demonstrates a novel application of urban planning and weather — climate models. It also raises viable questions concerning future planning strategies in urban environments in consideration of hydroclimate changes.