The strain dependent critical current of high field superconductors for fusion energy applications

All superconductors in high field magnets operating above 12 T are brittle and subjected to large strains because of the differential thermal contraction between component parts on cool-down and the large Lorentz forces produced in operation. The continuous scientific requirement for higher magnetic fields in superconducting energy-efficient magnets, in applications such as fusion, means we must understand and control the high sensitivity of critical current density $J_\mathrm{c}$ to strain $\varepsilon$. This thesis presents detailed $J_\mathrm{c} \left( B,T,\varepsilon,\theta \right)$ transport measurements as a function of field $B$, temperature $T$, strain $\varepsilon$ and angle $\theta$ with respect to the applied magnetic field, on high field superconductors that include the very widely observed inverted parabolic dependence for $J_\mathrm{c} \left( \varepsilon \right)$. It is usually assumed that a coincidence occurs between the Fermi energy and a peak in the density of states in the unstrained state which leads to a peak in the superconducting properties in the unstrained state. The long-standing interpretation of $J_\mathrm{c} \left( \varepsilon \right)$ data attributes the inverted parabolic strain behaviour to the averaged response of the underlying material. Features of the data in this work are identified in both HTS REBCO tape and LTS A15 wires which show that both of these assumptions are incorrect. A new analysis is presented which shows the inverted parabolic nature of $J_\mathrm{c} \left( \varepsilon \right)$ is the result of competition between domains with opposing strain dependencies and successfully accounts for the features of the data incompatible with standard assumptions. It is concluded that the origin of the competing domains in REBCO tape lies in twinned domains and in A15 wires is caused by percolative current flow across grain boundaries orientated in different directions which respond to an applied strain in different manners due to the Poisson effect. This work provides fresh insight into how improvements might be made to high field superconductors under strain

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

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

The transfer and implementation of an Aboriginal Australian wellbeing program: a grounded theory study

Background: The concepts and standard practices of implementation, largely originating in developed countries, cannot necessarily be simply transferred into diverse cultural contexts. There has been relative inattention in the implementation science literature paid to the implementation of interventions targeting minority Indigenous populations within developed countries. This suggests that the implementation literature may be bypassing population groups within developed countries who suffer some of the greatest disadvantage. Within the context of Aboriginal Australian health improvement, this study considers the impact of political and cultural issues by examining the transfer and implementation of the Family Wellbeing program across 56 places over a 20-year period.\ud \ud Methods: A theoretical model of program transfer was developed using constructivist-grounded theory methods. Data were generated by conducting in-depth interviews with 18 Aboriginal and non-Aboriginal research respondents who had been active in transferring the program. Data were categorised into higher order abstract concepts and the core impetus for and process of program transfer were identified.\ud \ud Results: Organizations transferred the program by using it as a vehicle for supporting inside-out empowerment. The impetus to support inside-out empowerment referred to support for Aboriginal people's participation, responsibility for and control of their own affairs, and the associated ripple effects to family members, organizations, communities, and ultimately reconciliation with Australian society at large. Program transfer occurred through a multi-levelled process of embracing relatedness which included relatedness with self, others, and structural conditions; all three were necessary at both individual and organizational levels.\ud \ud Conclusions: Similar to international implementation models, the model of supporting inside-out empowerment by embracing relatedness involved individuals, organizations, and interpersonal and inter-organizational networks. However, the model suggests that for minority Indigenous populations within developed countries, implementation approaches may require greater attention to the empowering nature of the intervention and its implementation, and multiple levels of relatedness by individuals and organizations with self, others, and the structural conditions. Key elements of the theoretical model provide a useful blueprint to inform the transfer of other empowerment programs to minority Indigenous and other disadvantaged populations on a case-by-case basis