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

Hormonal enhancement of technetium-99m pertechnetate uptake in experimental Meckel's diverticulum

A canine model simulating Meckel's diverticulum was used to evaluate the effects of pentagastrin, glucagon, and a combination of the two hormones on the gastrointestinal localization of 99mTc. Pentagastrin produced accelerated uptake of the radionuclide in both the stomach and the ectopic gastric mucosa but resulted in early visualization of the duodenum and a “washout” effect on the radioisotope within the Meckel's diverticulum. Glucagon provided prolonged retention of the radionuclide in the stomach and ectopic mucosa and prevented duodenal visualization. A combination of both hormones produced increased activity in the stomach and experimental Meckel's and decreased duodenal filling. This enhanced target to background contrast and provided improved visualization fo the ectopic gastric mucosa

Improvement in male pelvis magnetic resonance image contouring following radiologist‐delivered training

Abstract Introduction The magnetic resonance linear accelerator (MRL) combines both magnetic resonance imaging and a linear accelerator, allowing for daily treatment adaptation. This study aimed to assess the impact of radiologist‐delivered training in magnetic resonance (MR) contouring of relevant structures within the male pelvis. Methods Two radiation oncologists, two radiation oncology registrars and seven radiation therapists completed contouring on 10 male pelvis MR datasets both pre‐ and post‐training. A 2‐hour MR anatomy training session was delivered by a radiologist, who also provided the ‘gold standard’ contours. The pre‐ and post‐training contours were compared against the gold standard with Dice similarity coefficient (DSC) and Hausdorff distances calculated; and the pre‐ and post‐confidence scores and timing were compared. Results The improvement in DSC were significant in prostate, rectum and seminal vesicles, with a post‐training median DSC of 0.87 ± 0.06, 0.92 ± 0.04 and 0.80 ± 0.14, respectively. The median Hausdorff improved with a median of 1.46 ± 0.78 mm, 0.52 ± 0.32 mm and 1.11 ± 0.86 mm for prostate, rectum and seminal vesicles, respectively. Bladder concordance was high both pre‐ and post‐training. Urethra contours improved post‐training, however, remained difficult to contour with a median post‐DSC of 0.51 ± 0.24. Overall, confidence scoring improved (P < 0.001) and timing decreased by an average of 4.4 ± 16.4 min post‐training. Conclusion Radiologist‐delivered training improved concordance of male pelvis contouring on MR datasets. Further work is required in the identification of urethra on MRs. These findings are of importance in the MRL adaptive workflow

Improvement in male pelvis magnetic resonance image contouring following radiologist-delivered training

Introduction: The magnetic resonance linear accelerator (MRL) combines both magnetic resonance imaging and a linear accelerator, allowing for daily treatment adaptation. This study aimed to assess the impact of radiologist-delivered training in magnetic resonance (MR) contouring of relevant structures within the male pelvis. Methods: Two radiation oncologists, two radiation oncology registrars and seven radiation therapists completed contouring on 10 male pelvis MR datasets both pre- and post-training. A 2-hour MR anatomy training session was delivered by a radiologist, who also provided the ‘gold standard’ contours. The pre- and post-training contours were compared against the gold standard with Dice similarity coefficient (DSC) and Hausdorff distances calculated; and the pre- and post-confidence scores and timing were compared. Results: The improvement in DSC were significant in prostate, rectum and seminal vesicles, with a post-training median DSC of 0.87 ± 0.06, 0.92 ± 0.04 and 0.80 ± 0.14, respectively. The median Hausdorff improved with a median of 1.46 ± 0.78 mm, 0.52 ± 0.32 mm and 1.11 ± 0.86 mm for prostate, rectum and seminal vesicles, respectively. Bladder concordance was high both pre- and post-training. Urethra contours improved post-training, however, remained difficult to contour with a median post-DSC of 0.51 ± 0.24. Overall, confidence scoring improved (P < 0.001) and timing decreased by an average of 4.4 ± 16.4 min post-training. Conclusion: Radiologist-delivered training improved concordance of male pelvis contouring on MR datasets. Further work is required in the identification of urethra on MRs. These findings are of importance in the MRL adaptive workflow.</p

Ultra-fast polymer optical fibre Bragg grating inscription for medical devices

201812 bcrcVersion of RecordPublishe

Sputtered titanium nitride films on titanium foam substrates as electrodes for high-power electrochemical capacitors

Electrochemical capacitors (ECs) with high-power capabilities and stable cycling can effectively improve the state of the art in power delivery and energy storage. In this study, we investigate reactively sputtered titanium nitride (TiN) electrodes on three-dimensional (3D) substrates with various electrolytes and high-rate cycling conditions. The electrode exhibits cycling stability with negligible capacitance fading after 5 000 cycles and a great rate capability, allowing the (dis)charge rate to extend from 0.1 to 10 V s−1 and retaining nearly 50 % of the capacitance in a three-electrode system. A symmetric device made with such electrodes is capable of working at a scan rate up to 100 V s−1, yielding a remarkable power density of 4.81×105 W kg−1 at 1.60 Wh kg−1. The energy density can be pushed to 168.03 Wh kg−1 at 4.03×104 W kg−1 by replacing the aqueous electrolyte with an organic one, and this can likely be further increased by electrolyte optimization. The material synthesis and device processing suggest that 3D TiN structures can enable a new class of high-power ECs with enhanced stability compared to their carbon- and pseudo- counterparts

Stress-induced phase transformation in shape memory ceramic nanoparticles

202103 bcrcVersion of RecordPublishe

The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue

Age-related macular degeneration (AMD) is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE) cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC)-derived RPE cells (RPESC-RPE) preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue. Whereas cells at all stages of differentiation tested rescued photoreceptor layer morphology, an intermediate stage of RPESC-RPE differentiation obtained after 4 weeks of culture was more consistent at vision rescue than progeny that were differentiated for 2 weeks or 8 weeks of culture. Our results indicate that the developmental stage of RPESC-RPE significantly influences the efficacy of RPE cell replacement, which affects the therapeutic application of these cells for AMD

Assessing for genetic and environmental effects on ruminant feed quality in barley (Hordeum vulgare)

Grain samples from a combined intermediate and advanced stage barley breeding trial series, grown at two sites in two consecutive years were assessed for detailed grain quality and ruminant feed quality. The results indicated that there were significant genetic and environmental effects for "feed" traits as measured using grain hardness, acid detergent fibre (ADF), starch and in-sacco dry matter digestibility (ISDMD) assays. In addition, there was strong genotypic discrimination for the regressed feed performance traits, namely Net Energy (NE) and Average Daily Gain (ADG). There was considerable variation in genetic correlations for all traits based on variance from the cultivars used, sites or laboratory processing effects. There was a high level of heritability ranging from 89% to 88% for retention, 60% to 80% for protein and 56% to 68% for ADF. However, there were only low to moderate levels of heritability for the feed traits, with starch 30-39%, ISDMD 55-63%, ADF 56-68%, particle size 47-73%, 31-48% NE and ADG 44-51%. These results suggest that there were real differences in the feed performance of barleys and that selection for cattle feed quality is potentially a viable option for breeding programs