Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

A Pedagogy for Critical Teacher Education: Facilitating Dialogue for Transformative Learning

The context for this documentary account is the preparation of teacher educators for critical multicultural teacher education (Kincheloe, 2008) or what Keating (2007) has called “transformational multiculturalism.” Specifically, we report on the experiences of teacher education doctoral students in a Critical Pedagogy seminar. In particular, our analysis is based on eight doctoral students’ experiences with a course assignment, called “Give it a Try.” Challenged to enact one or more of the concepts studied in the seminar and to reflect on what they learned from “giving it a try,” the students attempted to facilitate the transformation of unquestioned belief systems in a wide range of contexts. We report on what the students learned about their role in facilitating dialogue for transformative learning

Getting Beneath the Surface: Experiences and Challenges of First-Year Teachers Working to Become Warm Demanders

This qualitative study examined the contrasting experiences of two first-year teachers as they worked to become warm demanders in a low-income, predominantly African American school setting. Drawing on interviews, videos, and use of an observation tool, we examine teachers’ definitions of a warm demander, how their teaching practices reflected their beliefs, and the challenges they experienced as they worked to become warm demanders. The authors draw conclusions intended to enhance teacher preparation for high poverty, predominately minority settings

The CSTools (v4.0) toolbox : from climate forecasts to climate forecast information

Despite the wealth of existing climate forecast data, only a small part is effectively exploited for sectoral applications. A major cause of this is the lack of integrated tools that allow the translation of data into useful and skilful climate information. This barrier is addressed through the development of an R package. CSTools is an easy-to-use toolbox designed and built to assess and improve the quality of climate forecasts for seasonal to multi–annual scales. The package contains process-based state-of-the-art methods for forecast calibration, bias correction, statistical and stochastic downscaling, optimal forecast combination and multivariate verification, as well as basic and advanced tools to obtain tailored products. Due to the design of the toolbox in individual functions, the users can develop their own post-processing chain of functions as shown in the use cases presented in this manuscript: the analysis of an extreme wind speed event, the generation of seasonal forecasts of snow depth based on the SNOWPACK model and the post-processing of data to be used as input for the SCHEME hydrological model

Climate Services Toolbox (CSTools) v4.0: from climate forecasts to climate forecast information

International audienceAbstract. Despite the wealth of existing climate forecast data, only a small part is effectively exploited for sectoral applications. A major cause of this is the lack of integrated tools that allow the translation of data into useful and skillful climate information. This barrier is addressed through the development of an R package. Climate Services Toolbox (CSTools) is an easy-to-use toolbox designed and built to assess and improve the quality of climate forecasts for seasonal to multi-annual scales. The package contains process-based, state-of-the-art methods for forecast calibration, bias correction, statistical and stochastic downscaling, optimal forecast combination, and multivariate verification, as well as basic and advanced tools to obtain tailored products. Due to the modular design of the toolbox in individual functions, the users can develop their own post-processing chain of functions, as shown in the use cases presented in this paper, including the analysis of an extreme wind speed event, the generation of seasonal forecasts of snow depth based on the SNOWPACK model, and the post-processing of temperature and precipitation data to be used as input in impact models

Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study

Background: Existing clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence. Methods: In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero. Findings: 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (pT variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7–56% of carriers having a colorectal cancer penetrance of less than 20%, 9–44% having a penetrance of more than 80%, and only 10–19% having a penetrance of 40–60%. Interpretation: Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessments for precision prevention and early detection of colorectal cancer for people with Lynch syndrome. Funding: National Health and Medical Research Council, Australia

Search for Scalar Diphoton Resonances in the Mass Range 65−60065-600 GeV with the ATLAS Detector in pppp Collision Data at s\sqrt{s} = 8 TeVTeV

A search for scalar particles decaying via narrow resonances into two photons in the mass range 65–600 GeV is performed using $20.3\text{}\text{}{\mathrm{fb}}^{-1}$ of $\sqrt{s}=8\text{}\text{}\mathrm{TeV}$ $pp$ collision data collected with the ATLAS detector at the Large Hadron Collider. The recently discovered Higgs boson is treated as a background. No significant evidence for an additional signal is observed. The results are presented as limits at the 95% confidence level on the production cross section of a scalar boson times branching ratio into two photons, in a fiducial volume where the reconstruction efficiency is approximately independent of the event topology. The upper limits set extend over a considerably wider mass range than previous searches