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

Visual deficits in amblyopia constrain normal models of second-order motion processing

AbstractIt is well established that amblyopes exhibit deficits in processing first-order (luminance-defined) patterns. This is readily manifest by measuring spatiotemporal sensitivity (i.e. the “window of visibility”) to moving luminance gratings. However the window of visibility to moving second-order (texture-defined) patterns has not been systematically studied in amblyopia. To address this issue monocular modulation sensitivity (1/threshold) to first-order motion and four different varieties of second-order motion (modulations of either the contrast, flicker, size or orientation of visual noise) was measured over a five-octave range of spatial and temporal frequencies. Compared to normals amblyopes are not only impaired in the processing of first-order motion, but overall they exhibit both higher thresholds and a much narrower window of visibility to second-order images. However amblyopia can differentially impair the perception of some types of second-order motion much more than others and crucially the precise pattern of deficits varies markedly between individuals (even for those with the same conventional visual acuity measures). For the most severely impaired amblyopes certain second-order (texture) cues to movement in the environment are effectively invisible. These results place important constraints on the possible architecture of models of second-order motion perception in human vision

The Delivery of Water During Terrestrial Planet Formation

The planetary building blocks that formed in the terrestrial planet region were likely very dry, yet water is comparatively abundant on Earth. We review the various mechanisms proposed for the origin of water on the terrestrial planets. Various in-situ mechanisms have been suggested, which allow for the incorporation of water into the local planetesimals in the terrestrial planet region or into the planets themselves from local sources, although all of those mechanisms have difficulties. Comets have also been proposed as a source, although there may be problems fitting isotopic constraints, and the delivery efficiency is very low, such that it may be difficult to deliver even a single Earth ocean of water this way. The most promising route for water delivery is the accretion of material from beyond the snow line, similar to carbonaceous chondrites, that is scattered into the terrestrial planet region as the planets are growing. Two main scenarios are discussed in detail. First is the classical scenario in which the giant planets begin roughly in their final locations and the disk of planetesimals and embryos in the terrestrial planet region extends all the way into the outer asteroid belt region. Second is the Grand Tack scenario, where early inward and outward migration of the giant planets implants material from beyond the snow line into the asteroid belt and terrestrial planet region, where it can be accreted by the growing planets. Sufficient water is delivered to the terrestrial planets in both scenarios. While the Grand Tack scenario provides a better fit to most constraints, namely the small mass of Mars, planets may form too fast in the nominal case discussed here. This discrepancy may be reduced as a wider range of initial conditions is explored. Finally, we discuss several more recent models that may have important implications for water delivery to the terrestrial planets

Scotland's coast: Understanding past and present processes for sustainable management

The coastline of Scotland is extremely long and varied. It comprises most of the major types of coastal environment and includes machair, a sand dune system that is unique to the western seaboard of the British Isles. Such variety has its roots in the geology and sea level inheritance of Scotland and demonstrates that long‐term processes still exert a profound influence on coastal form and functioning. Understanding how these processes affect the coast and influence such diversity is essential to efficient coastal management, although it is also imperative that the vision, strategy and political will to deliver such management are also in place

Dispensing Rates of Four Common Hearing Aid Product Features: Associations With Variations in Practice Among Audiologists

The purpose of the study was to develop and examine a list of potential variables that may account for variability in the dispensing rates of four common hearing aid features. A total of 29 potential variables were identified and placed into the following categories: (1) characteristics of the audiologist, (2) characteristics of the hearing aids dispensed by the audiologist, (3) characteristics of the audiologist?s patient population, and (4) evidence-based practice grades of recommendation for each feature. The potentially associative variables then were examined using regression analyses from the responses of 257 audiologists to a dispensing practice survey. There was a direct relation between price and level of hearing aid technology with the frequency of dispensing product features. There was also a direct relation between the belief by the audiologist that a feature might benefit patients and the frequency of dispensing that feature. In general, the results suggested that personal differences among audiologists and the hearing aids audiologists choose to dispense are related more strongly to dispensing rates of product features than to differences in characteristics of the patient population served by audiologists. An additional finding indicated that evidence-based practice recommendations were inversely related to dispensing rates of product features. This finding, however, may not be the result of dispensing trends as much as hearing aid manufacturing trends