Search

Abstract Chronic HIV disease is associated with a fivefold increase in albuminuria outside of sub-Saharan Africa. However, very little is known about albuminuria risk among people living with HIV (PLWH) in sub-Saharan Africa. Therefore, we conducted a cross-sectional observational HIV clinic-based study of albuminuria among 1533 adults aged 21 years or older between January 2020 and January 2021 in Gaborone, Botswana. Clinical albuminuria was defined using a sex-based albumin‒creatinine ratio (ACR) of 25–355 mg/g for females and 17–250 mg/g for males. The study population mean age was 48.5 (SD 10.3) years, and 764/1533 (49.7%) were female. The overall prevalence of albuminuria was 20.7% (95% CI 18.7%, 22.8%). A higher proportion of males were more likely to be categorized as having albuminuria than females, 25% (95% CI 22.0, 28.2) versus 16.4% (95% CI 13.8,19.2), P value

Abstract Background Staff shortages limit access to health services. The bidirectional benefits of allied health clinical placements are understood in the domains of student learning, health service delivery, and future workforce development. Still, the benefits to current workforce outcomes remain unknown. This review provides insights into the effects of allied health student placements in acute and primary care settings, particularly on healthcare staff's knowledge and procedural skills. Methods This search was based on the integrative review process established by Whittemore and Knafl in 2005. In October 2023, the first author (MH) searched five major electronic databases: Medline-EBSCO, PubMed, CINAHL, Embase, and Scopus. The CLUSTER model was used to track additional references. The first three authors (MH, SM, and SC) were involved in screening, quality appraisal, and synthesis of the studies. Data were thematically synthesised and analysed. Results MeSH headings and keywords were used in key search areas: health education, health professional training, clinical placements, and allied health professions. The systematic search yielded 12 papers on allied health student placements across various healthcare settings in rural and metropolitan areas, with no high-quality methodologies measuring student placements' impact on staff knowledge and skills. Four main themes were identified from the analysis: meaningful student integration in service delivery, targeted educational support to healthcare staff, development of staff procedural skills and confidence, and the mechanisms of why student placements work in this aspect. Conclusions This review suggests that offering allied health student placement could be a promising approach to supporting rural healthcare staff in performing patient assessments and treatments proficiently and collaboratively. However, this requires further investigation to confirm.

Self-regulation has been shown to play a protective role against youth substance abuse, but less is known about its influence on bullying behavior. In the present study, we examined several forms of bullying (physical, social, cyber, and all forms combined) and roles (bullies, victims, and bully-victims). Students (N = 1977, ages 11 to 13) from 27 middle schools throughout the United States (US) completed an online self-reported assessment of bullying and its hypothesized etiologic determinants. Across the outcomes, analyses revealed that social bullying was most prevalent, followed by physical bullying and cyberbullying. For bullying roles, almost two-thirds of students reported bullying victimization, nearly one-quarter reported bullying perpetration, and one in five students reported both. Of those reporting perpetration, 9 of 10 reported being victimized. Multivariate logistic regression models were used to examine the associations between self-regulation, bystander intervention skills, and bullying. For all forms of bullying combined, self-regulation was protective against bullying perpetration (OR 0.51, 95% CI: 0.42, 0.63) and perpetration/victimization (OR 0.55, 95% CI: 0.44, 0.68), while bystander intervention skills were not protective. Similar patterns emerged for physical, social, and cyberbullying. Collectively, these findings indicate that building self-regulation skills may be a critical component of interventions aimed at preventing bullying among school-aged youth.

Abstract Background CBT is an effective treatment for depression, but access varies across the United Kingdom. Online CBT increases access. The INTERACT platform was designed to support patient engagement in CBT, enabling therapists to deliver high‐intensity CBT via typed instant messaging and allowing patients and therapists access to an integrated online library of resources during and between sessions. Methods The INTERACT trial aimed to evaluate this integrated approach to delivering CBT for primary care patients with depression. A nested qualitative study was conducted within the trial. Interviews were conducted with 20 patients who received the intervention, 9 therapists who delivered it and 3 therapist supervisors. Data were analysed using thematic analysis. Results The combination of receiving support from a therapist and having access to integrated online CBT resources enabled patients to better manage their depression. Platform benefits included the opportunity to review transcripts to clarify how to complete homework tasks and track progress in managing their depression. The typing process allowed reflection and a focused discussion. However, less could be covered than during an in‐person session, which reduced therapists’ expectations around goal setting. Patients who did not complete therapy struggled with the typing and found the CBT approach too demanding. Conclusion Findings highlight the importance of establishing patient and therapist goals and expectations about what can be achieved in CBT mediated by typing. Some patients are comfortable communicating via typing and are motivated to utilise online resources in between sessions. Exploring the benefits and challenges of typed CBT with patients will enable them to make an informed choice about referral for this novel approach to therapy. Patient or Public Contribution Patients, service users and members of the public were involved in the study design and management. Substantial pilot work gathered stakeholder feedback and informed the design of the intervention, before undertaking the RCT. Coauthor P.L. is a service user representative co‐applicant and member of the management group responsible for developing the intervention and the trial. Two PPI members sit on the Independent Steering Committee. PPI members provided valuable feedback on the study resources and documents.

The radio frequency spectrum serves as a fundamental resource for wireless communication, encompassing various frequency bands allocated for diverse services and applications. Dynamic spectrum management (DSM) is essential to optimise the utilisation of this limited and valuable natural resource, with the aim of improving performance and adapting to changing wireless communication demands. Traditional static spectrum allocation methods have shown inefficiencies, leading to spectrum scarcity and under-utilisation. To address these challenges, the integration of blockchain and Cognitive Radio (CR) technologies has emerged as a promising approach. Blockchain, with its decentralised and secure attributes, can improve transparency and trust in spectrum allocation processes, while CR enables intelligent spectrum sensing and allocation to maximise utilisation. However, this promising approach comes with its own critical challenges, especially when dealing with the 6th Generation (6G) mobile communication. These challenges are related to the fact that the blockchain ecosystem needs to be interoperable and scalable enough to be compatible with the 6G high-demand and substantial resources. Specifically, integrating blockchain with CR requires efficient interoperability techniques where blockchain can easily and effectively interact with the CR platforms as well as radio spectrum environments. Furthermore, the spectrum management system over 6G networks needs to be designed in a way where massive 6G resources can be accommodated and managed without having any service performance degradation. This paper introduces a novel radio spectrum management model in 6G networks, named as BSM-6G, which integrates blockchain technology with CR where interoperability is preserved and scalability is maximised. Specifically, the proposed BSM-6G model merges blockchain’s transparent record keeping with CR’s intelligent spectrum management capabilities. To overcome the interoperability issue, BSM-6G provides an interoperable blockchain Oracle approach which facilitates the real-time interaction among the blockchain platform, the CR, and any data sources off-chain. This paper details all the technical and procedural challenges when implementing the proposed interoperability Oracle approach. To address the scalability challenge, BSM-6G utilizes the Proof-of-History (PoH) consensus protocol to align with the requirements of DSM in advanced networks like Beyond 5th Generation (B5G) and 6G. Evaluation results indicate that BSM-6G offers viable and less complex blockchain Oracle integration architecture measured by the technical implementation of BSM-6G, as well as low interoperability cost measured by transaction response time and transaction fee cost. Compared to state-of-the-art spectrum-based blockchain systems, BSM-6G shows a high scalable DSM-based blockchain in 6G networks measured by transactions per second (TPS).

Introduction: Monovalent COVID-19 boosters lower the risk of COVID-19 disease, infection, hospitalization, and death. This study examined associations between exposure to a booster public education campaign (the booster campaign) and the increases in booster uptake and reduced length of time until booster uptake among U.S. adults. Methods: Data included a national survey panel of U.S. adults and booster campaign paid media (i.e., digital impressions and TV gross rating points) from September 2021 to May 2022. Multilevel logistic regression models examined the association between exposure to the booster campaign and the likelihood of booster uptake. A Cox proportional hazard model evaluated the association between the booster campaign and booster uptake timing. Interaction terms between the booster campaign media variables and first-dose COVID-19 vaccine date examined differential effects of the booster campaign based on when individuals received their first dose. Results: Interactions between first-dose vaccination date and the booster campaign were statistically significant for cumulative digital impressions (ß=4.75e-08; 95% CIs=5.93e-09, 8.90e-08) and TV gross rating points (ß = 4.62e-05; 95% CIs=5.09e-06, 8.73e-05), suggesting that booster uptake was strongest among those who received their first-dose COVID-19 vaccine later. Booster campaign cumulative digital impressions and TV gross rating points were associated with accelerated booster uptake among those with later first-dose vaccination dates (digital: ß=9.98e-08; 95% CIs=2.70e-08, 1.73e-07; TV: ß=0.0001; 95% CIs=2.80e-05, 0.0002), relative to those with earlier first-dose vaccination dates. Conclusions: The booster campaign may have increased monovalent booster uptake and reduced how long individuals waited until getting their booster. Public education campaigns show promise in stemming the tide of pandemic fatigue and increasing booster confidence.

Abstract Background Self-harm is an important predictor of a suicide death. Culturally appropriate strategies for the prevention of self-harm and suicide are needed but the evidence is very limited from low- and middle-income countries (LMICs). This study aims to investigate the effectiveness of a culturally adapted manual-assisted problem-solving intervention (CMAP) for patients presenting after self-harm. Methods This was a rater-blind, multicenter randomised controlled trial. The study sites were all participating emergency departments, medical wards of general hospitals and primary care centres in Karachi, Lahore, Rawalpindi, Peshawar, and Quetta, Pakistan. Patients presenting after a self-harm episode (n = 901) to participating recruitment sites were assessed and randomised (1:1) to one of the two arms; CMAP with enhanced treatment as usual (E-TAU) or E-TAU. The intervention (CMAP) is a manual-assisted, cognitive behaviour therapy (CBT)-informed problem-focused therapy, comprising six one-to-one sessions delivered over three months. Repetition of self-harm at 12-month post-randomisation was the primary outcome and secondary outcomes included suicidal ideation, hopelessness, depression, health-related quality of life (QoL), coping resources, and level of satisfaction with service received, assessed at baseline, 3-, 6-, 9-, and 12-month post-randomisation. The trial is registered on ClinicalTrials.gov. NCT02742922 (April 2016). Results We screened 3786 patients for eligibility and 901 eligible, consented patients were randomly assigned to the CMAP plus E-TAU arm (n = 440) and E-TAU arm (N = 461). The number of self-harm repetitions for CMAP plus E-TAU was lower (n = 17) compared to the E-TAU arm (n = 23) at 12-month post-randomisation, but the difference was not statistically significant (p = 0.407). There was a statistically and clinically significant reduction in other outcomes including suicidal ideation (− 3.6 (− 4.9, − 2.4)), depression (− 7.1 (− 8.7, − 5.4)), hopelessness (− 2.6 (− 3.4, − 1.8), and improvement in health-related QoL and coping resources after completion of the intervention in the CMAP plus E-TAU arm compared to the E-TAU arm. The effect was sustained at 12-month follow-up for all the outcomes except for suicidal ideation and hopelessness. On suicidal ideation and hopelessness, participants in the intervention arm scored lower compared to the E-TAU arm but the difference was not statistically significant, though the participants in both arms were in low-risk category at 12-month follow-up. The improvement in both arms is explained by the established role of enhanced care in suicide prevention. Conclusions Suicidal ideation is considered an important target for the prevention of suicide, therefore, CMAP intervention should be considered for inclusion in the self-harm and suicide prevention guidelines. Given the improvement in the E-TAU arm, the potential use of brief interventions such as regular contact requires further exploration.

Recent studies suggest an increased risk of reinfection with the SARS-CoV-2 Omicron variant compared with previous variants, potentially due to an increased ability to escape immunity specific to older variants, high antigenic divergence of Omicron from earlier virus variants as well as its altered cell entry pathway. The present study sought to investigate epidemiological evidence for differential SARS-CoV-2 reinfection intervals and incidence rates for the Delta versus Omicron variants within Wales. Reinfections in Wales up to February 2022 were defined using genotyping and whole genome sequencing. The median inter-infection intervals for Delta and Omicron were 226 and 192 days, respectively. An incidence rate ratio of 2.17 for reinfection with Omicron compared to Delta was estimated using a conditional Poisson model, which accounted for several factors including sample collection date, age group, area of residence, vaccination and travel status. These findings are consistent with an increased risk of reinfection with the Omicron variant, and highlight the value of monitoring emerging variants that have the potential for causing further waves of cases.

ObjectivesCOVID-19 has been at the forefront of global concern since its emergence in December of 2019. Determining the social factors that drive case incidence is paramount to mitigating disease spread. We gathered data from the Social Vulnerability Index (SVI) along with Democratic voting percentage to attempt to understand which county-level sociodemographic metrics had a significant correlation with case rate for COVID-19.MethodsWe used elastic net regression due to issues with variable collinearity and model overfitting. Our modelling framework included using the ten Health and Human Services regions as submodels for the two time periods 22 March 2020 to 15 June 2021 (prior to the Delta time period) and 15 June 2021 to 1 November 2021 (the Delta time period).ResultsStatistically, elastic net improved prediction when compared to multiple regression, as almost every HHS model consistently had a lower root mean square error (RMSE) and satisfactory R2 coefficients. These analyses show that the percentage of minorities, disabled individuals, individuals living in group quarters, and individuals who voted Democratic correlated significantly with COVID-19 attack rate as determined by Variable Importance Plots (VIPs).ConclusionsThe percentage of minorities per county correlated positively with cases in the earlier time period and negatively in the later time period, which complements previous research. In contrast, higher percentages of disabled individuals per county correlated negatively in the earlier time period. Counties with an above average percentage of group quarters experienced a high attack rate early which then diminished in significance after the primary vaccine rollout. Higher Democratic voting consistently correlated negatively with cases, coinciding with previous findings regarding a partisan divide in COVID-19 cases at the county level. Our findings can assist regional policymakers in distributing resources to more vulnerable counties in future pandemics based on SVI.

Abstract Background During the COVID-19 pandemic, face-to-face delivery of education in schools across Wales was disrupted with repeated school closures to limit risk of infection. Evidence describing the incidence of infection amongst school staff during times when schools were open is limited. A previous research study found infection rates were higher in English primary school settings when compared with secondary. An Italian study suggested teachers weren’t at greater risk of infection in comparison to the general population. The aim of this study was to identify whether educational staff had higher incidence rates than their counterparts in the general population in Wales, and secondly whether incidence rates amongst staff differed between primary and secondary school settings and by teacher age. Methods We performed a retrospective observational cohort study using the national case detection and contact tracing system implemented during the COVID pandemic. Age stratified person-day COVID-19 incidence rates amongst teaching staff linked to primary or secondary schools in Wales were calculated for the autumn and summer terms during 2020–2021. Results The observed pooled COVID-19 incidence rates for staff across both terms was 23.30 per 100,000 person days (95% CI: 22.31–24.33). By comparison, the rate in the general population aged 19–65, was 21.68 per 100,000 person days (95%: CI 21.53–21.84). Incidence among teaching staff was highest in the two youngest age groups (

Abstract Epidemiologic surveillance of circulating SARS-CoV-2 variants is essential to assess impact on clinical outcomes and vaccine efficacy. Whole genome sequencing (WGS), the gold-standard to identify variants, requires significant infrastructure and expertise. We developed a digital droplet polymerase chain reaction (ddPCR) assay that can rapidly identify circulating variants of concern/interest (VOC/VOI) using variant-specific mutation combinations in the Spike gene. To validate the assay, 800 saliva samples known to be SARS-CoV-2 positive by RT-PCR were used. During the study (July 2020-March 2022) the assay was easily adaptable to identify not only existing circulating VAC/VOI, but all new variants as they evolved. The assay can discriminate nine variants (Alpha, Beta, Gamma, Delta, Eta, Epsilon, Lambda, Mu, and Omicron) and sub-lineages (Delta 417N, Omicron BA.1, BA.2). Sequence analyses confirmed variant type for 124/124 samples tested. This ddPCR assay is an inexpensive, sensitive, high-throughput assay that can easily be adapted as new variants are identified.

IntroductionThe Agile Nudge University is a National Institute on Aging-funded initiative to engineer a diverse, interdisciplinary network of scientists trained in Agile processes.MethodsMembers of the network are trained and mentored in rapid, iterative, and adaptive problem-solving techniques to develop, implement, and disseminate evidence-based nudges capable of addressing health disparities and improving the care of people living with Alzheimer's disease and other related dementias (ADRD).ResultsEach Agile Nudge University cohort completes a year-long online program, biweekly coaching and mentoring sessions, monthly group-based problem-solving sessions, and receives access to a five-day Bootcamp and the Agile Nudge Resource Library.DiscussionThe Agile Nudge University is evaluated through participant feedback, competency surveys, and tracking of the funding, research awards, and promotions of participating scholars. The Agile Nudge University is compounding national innovation efforts in overcoming the gaps in the ADRD discovery-to-delivery translational cycle.

Bullying is a widespread public health problem with significant behavioral and mental health consequences. The current study tested the effectiveness of combining interactive digital material for students, educators, and parents with class sessions to prevent bullying among middle school students. Fourteen middle schools were randomly assigned to intervention and comparison conditions. Both conditions received a classroom-based drug and violence prevention program that taught social skills, self-management skills, and social resistance skills. The intervention condition included class material on bullying and an educational video game for students that reinforced the classroom program; it also included digital material on bullying for parents and school staff. All students completed online pre- and post-test surveys to assess bullying-related behavior, knowledge, and life skills. Results indicated that students in the intervention schools reported significantly less bullying and cyberbullying perpetration and increased life skills knowledge relative to comparison schools. This study provides evidence that a school-based drug abuse and violence prevention program, when enhanced with a set of digital tools for students, parents, and school staff, holds considerable potential for addressing bullying among middle school adolescents.

Abstract Background Having a research-engaged health and medical workforce is associated with improvements in clinical outcomes for patients. As such, there has been significant government investment internationally to support health care organisations and services to increase staff engagement with research. Objectives This scoping review sought to provide an overview of the literature describing strategies employed to increase research engagement by health care providers and organisations, and to undertake a qualitative analysis to generate a list of research engagement strategies. Methods A scoping review using systematic search strategies was undertaken to locate peer-review publications and grey literature related to research engagement by health care providers and organisations. Research engagement was defined as a ‘deliberate set of intellectual and practical activities undertaken by health care staff and organisations to conduct research’. A database search of electronic records was performed with no limit on publication date. Publications were included regardless of study type (excluding systematic reviews) and categorised as either databased (presenting data or new analysis of existing data) and non-databased (no new data or analyses). Databased publications were further classified according to study type, study design and setting. A qualitative synthesis using a Framework Approach was undertaken with all studies that described a strategy to improve research engagement. Results A total of 152 publications were included in this study with 54% categorised as non-databased. Of the databased articles, the majority (72%) were descriptive studies describing prevalence of correlates of research engagement, 17 (25%) described intervention studies where only two were controlled studies. The following research engagement strategies were identified: i) dual skilled team/staff, ii) resources or physical infrastructure, iii) incentives, iv) leadership support of research, v) education/training, vi) networks, vii) forming partnerships or collaborations and viii) overall leadership structure of entity. Conclusions The literature on research engagement is primarily opinion-based and descriptive in nature. To provide the evidence needed to inform strategies, this needs to progress beyond descriptive to more rigorous well-designed intervention research.

Breast carcinoma (BCa) remains the second most common cause of cancer-related death among American women. Whereas estrogen receptor (ER) expression is typically regarded as a favorable prognostic indicator, a significant proportion of ER(+) patients still experience either de novo or acquired endocrine resistance. Previously, we have shown that the loss of orphan nuclear receptor NURR1 expression is associated with neoplastic transformation of the breast epithelium and shorter relapse-free survival (RFS) among systemically treated breast cancer (BCa) patients. Here, we further ascertain the prognostic value of NURR1 in BCa, and its differential expression among Black and White female BCa patients. We assessed the expression of NURR1 mRNA in BCa patients using the Cancer Genome Atlas (TGCA) and compared the occurrence of basal-like cancer and luminal A breast cancer subtypes. Expression levels were further stratified according to racial identity of the patient. We next assessed the correlation of NURR1 expression with Oncotype DX prognostic markers, and the association of NURR1 expression with relapse free survival in patients treated with endocrine therapy. Our study shows that NURR1 mRNA expression is differentially correlated with luminal A vs. basal-like cancer BCa and is predictive of poor relapse-free survival, confirming a similar trend observed in our previous studies using microarray data. NURR1 expression was positively correlated with expression of Oncotype DX biomarkers associated with estrogen responsiveness, while being inversely correlated with biomarkers associated with cell proliferation. Furthermore, we observed that NURR1 expression was positively associated with greater relapse-free survival at 5 years among patients treated with endocrine therapy. Interestingly, we found that among Black women with luminal A BCa, NURR1 expression was repressed in comparison to White women with the same subtype.

Abstract Background Escherichia coli (E. coli) is a promising host for production of recombinant proteins (including antibodies and antibody fragments) that don’t require complex post-translational modifications such as glycosylation. During manufacturing-scale production of a one-armed antibody in E. coli (periplasmic production), variability in the degree of reduction of the antibody’s disulfide bonds was observed. This resulted in variability in the free thiol content, a potential critical product quality attribute. This work was initiated to understand and prevent the variability in the total free thiol content during manufacturing. Results In this study, we found that the reduction in antibody’s disulfide bonds was observed to occur during homogenization and the ensuing homogenate hold step where in the antibody is exposed to redox enzymes and small molecule reductants present in homogenate. Variability in the downstream processing time between the start of homogenization and end of the homogenate hold step resulted in variability in the degree of antibody disulfide bond reduction and free thiol content. The disulfide bond reduction in the homogenate is catalyzed by the enzyme disulfide bond isomerase C (DsbC) and is highly site-specific and occurred predominantly in the intra-chain disulfide bonds present in the Fc CH2 region. Our results also imply that lack of glycans in E. coli produced antibodies may facilitate DsbC accessibility to the disulfide bond in the Fc CH2 region, resulting in its reduction. Conclusions During E. coli antibody manufacturing processes, downstream processing steps such as homogenization and subsequent processing of the homogenate can impact degree of disulfide bond reduction in the antibody and consequently product quality attributes such as total free thiol content. Duration of the homogenate hold step should be minimized as much as possible to prevent disulfide bond reduction and free thiol formation. Other approaches such as reducing homogenate temperature, adding flocculants prior to homogenization, using enzyme inhibitors, or modulating redox environments in the homogenate should be considered to prevent antibody disulfide bond reduction during homogenization and homogenate processing steps in E. coli antibody manufacturing processes.

BackgroundFarmers have higher rates of depression than nonfarmers and higher rates of suicide than the general population. Several barriers to help seeking have been identified in farmers, which may be overcome by offering web-based mental health support. Computerized cognitive behavioral therapy (cCBT) is an effective intervention used to prevent and treat mild to moderate depression but has not been evaluated in the farming community. ObjectiveThis study explored the feasibility of delivering a cCBT course tailored to farmers using a mixed methods approach. MethodsFarmers (aged ≥18 years) with no, minimal, or moderately severe depressive symptoms (Patient Health Questionnaire–9 [PHQ-9] score

BackgroundLateral flow tests (LFTs) have been used to screen for SARS-CoV2 in Wales since January 2021. Between May and August 2021, adult care home staff policy was for biweekly Innova LFT and weekly Polymerase Chain Reaction (PCR) testing while asymptomatic. We estimated test performance of LFTs conducted in adult care home staff using PCR tests as a reference standard.MethodsTest results from surveillance data were matched by individual where both LFT and PCR were taken on the same day. We calculated sensitivity, specificity, positive and negative predictive values, and agreement using Matthew's correlation coefficient. Ct values of positive PCR results were compared by matched LFT result. Analysis was conducted using R v4.1.3.ResultsWe analysed 115,593 test pairs, 499 (0.43%) of which were PCR positive. Median age was 48 (IQR: 22) and 85.00% of the study population were female. Test result agreement was 99.59% (95%CI 99.55-99.63; MCC: 0.38, pConclusionsSpecificity and negative predictive value were high in an asymptomatic population of care home staff indicating this test is an effective tool for identifying cases of SARS-CoV-2 infection during periods of high prevalence where transmission is likely, due to the presence of high viral loads. Positive predictive value results are lower than existing literature yet should be considered in light of the asymptomatic study population and low prevalence (under 1%) at the time most of these tests were conducted. Performance improved at times of higher prevalence during the study. These results suggest that whilst lateral flow tests are effective for identifying SARS-COV-2 infections with high viral loads, they are not effective at identifying cases with a low viral load. When an LFT provides a negative result, false negatives should be considered and additional diagnostic tests performed.

This paper presents the realization of a robotic workcell capable of autonomous, flexible, fabrication of complete, full-scale, functional mechatronic systems. Using a 6-DOF robotic arm with a hybrid Additive Manufacturing (AM)/Pick and Place (PnP) end effector, the workcell can rapidly print enclosures, insert and wire functional electronics, and embed them into the printed structure. The workcell's scalable control system, digital workflow for creating assembly instructions, hybrid AM/PnP toolhead design, and autonomous part tending mechanism are detailed. In addition, a modular electronics infrastructure is presented to enable facile, error-free robotic wiring of large-gauge copper wire. The workcell's ability to manufacture is verified in a case study wherein it is used to autonomously fabricate a variety of Unmanned Aerial Systems (UASs). In the study, the workcell produces a functional quadrotor drone, releases the drone from the workcell, and allows the drone to record the workcell constructing a second, different drone - all without human involvement. The resulting workcell, which combines digitally-integrated manufacturing, robotics and automation, and hybrid process manufacturing, enables autonomous manufacture of complete, functional mechatronic systems that are tailored to custom design needs in a just-in-time manner.

To inform the public and policy makers, we investigated and compared the risk of cerebral venous sinus thrombosis (CVST) after SARS-Cov-2 vaccination or infection using a national cohort of 2,643,699 individuals aged 17 y and above, alive, and resident in Wales on 1 January 2020 followed up through multiple linked data sources until 28 March 2021. Exposures were first dose of Oxford-ChAdOx1 or Pfizer-BioNTech vaccine or polymerase chain reaction (PCR)-confirmed SARS-Cov-2 infection. The outcome was an incident record of CVST. Hazard ratios (HR) were calculated using multivariable Cox regression, adjusted for confounders. HR from SARS-Cov-2 infection was compared with that for SARS-Cov-2 vaccination. We identified 910,556 (34.4%) records of first SARS-Cov-2 vaccination and 165,862 (6.3%) of SARS-Cov-2 infection. A total of 1,372 CVST events were recorded during the study period, of which 52 (3.8%) and 48 (3.5%) occurred within 28 d after vaccination and infection, respectively. We observed slight non-significant risk of CVST within 28 d of vaccination [aHR: 1.34, 95% CI: 0.95-1.90], which remained after stratifying by vaccine [BNT162b2, aHR: 1.18 (95% CI: 0.63-2.21); ChAdOx1, aHR: 1.40 (95% CI: 0.95-2.05)]. Three times the number of CVST events is observed within 28 d of a positive SARS-Cov-2 test [aHR: 3.02 (95% CI: 2.17-4.21)]. The risk of CVST following SARS-Cov-2 infection is 2.3 times that following SARS-Cov-2 vaccine. This is important information both for those designing COVID-19 vaccination programs and for individuals making their own informed decisions on the risk-benefit of vaccination. This record-linkage approach will be useful in monitoring the safety of future vaccine programs.

Traditional, limited purpose grey infrastructure has failed to address the world's interrelated water challenges. Improving water security will increasingly require more integrated responses. This paper examines large-scale green infrastructure (LSGI), planned natural or hybrid systems that materially affect water security at the watershed scale, as one such response. This paper examines key challenges for governing and financing LSGI, which hinder its broader use. We report on four case studies located in the United States where LSGI is being employed to improve water security. Through analysis of these case studies and related literature, we identify three themes important for LSGI governance: cost sharing, performance monitoring, and legitimization. First, we hypothesize that formal cost sharing based on the multiple benefits LSGI provides could enable wider adoption, but find that in these examples cost sharing is limited and informal. Second, our research suggests that expanding performance monitoring to encompass key secondary benefits could help clarify how the benefits and burdens of a project are distributed across stakeholders, facilitate cost sharing, and enhance project legitimacy. Finally, LSGI will require further legitimization – developing a broader perception that LSGI is an appropriate alternative or complement to grey infrastructure – to develop as a viable contributor to water security. HIGHLIGHTS Large-scale green infrastructure (LSGI) has promise to address complex water security challenges.; LSGI represents a paradigm shift from traditional grey infrastructure.; Case studies suggest that governance of LSGI lacks maturity, gating wider adoption and diffusion.; Novel funding models, improved performance monitoring, and legitimization at multiple scales must be addressed to increase the adoption and diffusion of LSGI.;

Purpose: Stereotactic magnetic resonance (MR)–guided adaptive radiation therapy (SMART) for prostate cancer allows for MR-based contouring, real-time MR motion management, and daily plan adaptation. The clinical and dosimetric benefits associated with prostate SMART remain largely unknown. Methods and Materials: A phase 1 trial of prostate SMART was conducted with primary endpoints of safety and feasibility. An additional cohort of patients similarly treated with prostate SMART were included in the analysis. SMART was delivered to 36.25 Gy in 5 fractions to the prostate ± seminal vesicles using the MRIdian linear accelerator system (ViewRay, Inc). Rates of urinary and gastrointestinal toxic effects and patient-reported outcome measures were assessed. Dosimetric analyses were conducted to evaluate the specific benefits of daily plan adaptation. Results: The cohort included 22 patients (n = 10 phase 1, n = 12 supplemental) treated in 110 fractions. Median follow-up was 7.9 months. Acute grade 2 urinary and gastrointestinal toxic effects were observed in 22.7% and 4.5%, respectively, and 4.5% and 0%, respectively, at last follow-up. No grade 3+ events were observed. Expanded Prostate Cancer Index-26 urinary obstructive scores decreased during SMART (mean, 9.3 points; P = .03) and returned to baseline by 3 months. No other significant changes in patient-reported outcome measures were observed. One-hundred percent of fractions required plan adaptation owing to exceeding organ-at-risk metrics (68%) or suboptimal target coverage (33%) resulting from anatomic changes. Minimum acceptable planning target volume, rectal, bladder, and urethra/bladder neck metrics were violated in 24%, 20%, 24%, and 33% of predicted plans, respectively; 0% of reoptimized plans violated metrics. Underlying causes for deficient dosimetry before reoptimization included changes in bladder filling, seminal vesicle position, prostate volume (median 4.7% increase by fraction 3; range, 0%-56%), and hotspots shifting into urethra/bladder neck. Conclusions: Prostate SMART results in low risk of acute toxic effects with improvements in target and organ-at-risk dosimetry. The clinical benefits resulting from daily plan adaptation, including urethra/bladder neck protection, warrant further investigation.

BackgroundEffective school-based programs for preventing substance abuse offer considerable public health potential. Yet limited class time and uneven implementation fidelity can be barriers to widespread adoption and high-quality implementation. A hybrid digital approach may be effective and help address these barriers.ObjectiveTo evaluate the effectiveness of a hybrid substance abuse prevention program for middle school students consisting of e-learning modules and in-person class sessions.DesignTwenty-three United States (U.S.) middle schools were randomly assigned either to an intervention condition (13 schools) or a treatment-as-usual control condition (10 schools) where standard health education material was delivered. There were 1,447 participants who completed the pre-test and post-test assessments, of which 48.3% were male and 51.7% female.InterventionThe hybrid digital intervention consisted of 14 brief e-learning modules and six classroom sessions adapted from an evidence-based program designed for classroom implementation to increase knowledge of adverse consequences of substance use and improve social skills, personal coping skills, and skills for resisting social influences to smoke, drink, or use drugs.MeasuresParticipating students completed online pre-test and post-test surveys to assess substance use, knowledge, and life skills.ResultsThere were significant reductions in substance use for the hybrid digital condition compared to the control condition as well as significant increases in health knowledge, skills knowledge, and life skills.ConclusionsA hybrid digital approach to substance abuse prevention is effective and offers potential for overcoming common barriers to widespread adoption and high-quality implementation.

There is limited evidence on the efficacy of Cognitive Behavioral Therapy (CBT) based guided self-help programs to improve low mood and anxiety in Pakistani adolescents. The aims of the current study were to assess the effectiveness of an eight week low intensity CBT-based guided self-help program, Living Life to the Full (LLTTF) on depression, anxiety and social functioning among secondary school adolescents in Pakistan. Fifty-six participants were randomly allocated to immediate (n = 28) and delayed access (n = 28) groups. Measures of depression, anxiety and social functioning were collected at baseline, post intervention and three months follow-up. There were significant improvements in measures of depression (t = -3.47, p < 0.01; d = 1.0), anxiety (t = -6.55, p < 0.001; d = 1.91) and social functioning (t = -4.28, p < 0.001) between immediate access and delayed access groups. These differences remained significant at three months follow-up. The study suggests that the Urdu LLTTF book course delivered in classes is effective for reducing depression and anxiety as well as improving social function among adolescents in Pakistan.

Anaplasma phagocytophilum is an emerging, Gram-negative, and obligate intracellular pathogen that is infrequently implicated as a causative agent of community-acquired pneumonia. In this paper, we report about an immunocompetent patient from the community who presented with fever, cough, and shortness of breath. Chest X-ray and CT showed bilateral lung infiltrates. Extensive workup for other common and uncommon causes of pneumonia was positive for anaplasmosis. The patient recovered completely with doxycycline therapy. In our literature review, we find that in 80% of reported cases of anaplasmosis pneumonia, empiric treatment did not contain doxycycline, which in some cases led to acute respiratory distress syndrome. Clinicians in tick-borne disease endemic regions should be aware of this unusual presentation of anaplasmosis in order to be able to select appropriate antimicrobial regimens and initiate timely management.

Background Standardized letters of recommendation (SLOR) have become common features of the medical school to residency transition. Research has shown many advantages over the narrative letter of recommendation including improved letter-writing efficiency, ease of interpretation, and improved reliability as performance predictors. Currently, at least four specialties require fellowship SLORs. Internal medicine adopted its SLOR in 2017. Previous research showed fellowship program directors’ satisfaction with the 2017 guidelines. Little is known about residency program directors’ acceptance and adherence to the guidelines. Objectives The study sought to assess the adoption rate of each component, barriers to adoption, time commitment, and alignment with intended goals of the guidelines. Methods Anonymous survey links were posted to an internal medicine discussion forum prior to the guidelines in spring 2017 and twice following the guidelines in fall 2018 and winter 2019. Two-sample tests of proportions were used to compare respondent characteristics with known survey population data. Pre- and post-survey comparisons were assessed for statistical significance with Pearson chi-squared statistic. Results The response rate varied from 30% to 35% for each survey period. Medical knowledge, patient care, interpersonal and communication skills, professionalism, and scholarly activity were reported frequently (>96%) at baseline. Inclusion of residency program characteristics, systems-based practice, practice-based learning and improvement, and skills sought to master increased over the study period. Conclusions The new guidelines improved uniform reporting of all core competency data. Overall, the gains were modest, as many pre-survey respondents reported high rates of including components within the guidelines.

So far most of the de novo designed proteins are for single states only. Here, the authors present the de novo design and crystal structure determination of a coiled-coil peptide that assembles into multiple, distinct conformational states under the same conditions and further characterise its properties with biophysical experiments, NMR and MD simulations.

Abstract Background Universal school-based prevention programs for alcohol, tobacco, and other drug use are typically designed for all students within a particular school setting. However, it is unclear whether such broad-based programs are effective for youth at risk for substance use and violence in juvenile justice settings. Method The present study tested the feasibility, appropriateness, and efficacy of a preventive intervention to reduce risk factors for substance use and delinquency among youth in juvenile justice diversionary settings by promoting positive youth development and building personal strengths and prosocial relationships. Participants in the study (N = 288) were predominantly male (69%) and in the 9th grade (14 years old) or higher (91%), received the preventive intervention, and completed confidential questionnaires at the pre-test and post-test. Results The majority of youth who participated in the intervention rated the program topics (77.9%) and activities (72%) as appropriate for their age, would recommend it to their peers (73.6%), and would use the skills learned in the future (85.4%). Comparison of post-test adjusted means revealed that the prevention program had a significant positive impact on key knowledge, attitudes, and skills including goal-setting, stress-management, and communication skills. Conclusions The findings indicate that an evidence-based prevention approach adapted for youth diversionary settings can be effectively implemented and well-received by participating youth, and can produce positive changes in psychosocial skills and protective factors known to prevent multiple risk behaviors among youth. Future efforts to implement substance use prevention in community juvenile justice settings may benefit from highlighting a positive youth development, skills-based approach.

Introduction Suicide is a global health concern. Sociocultural factors have an impact on self-harm and suicide rates. In Pakistan, both self-harm and suicide are considered as criminal offence’s and are condemned on both religious and social grounds. The proposed intervention ‘Youth Culturally Adapted Manual Assisted Problem Solving Training (YCMAP)’ is based on principles of problem-solving and cognitive–behavioural therapy. YCMAP is a brief, culturally relevant, scalable intervention that can be implemented in routine clinical practice if found to be effective.Method and analysis A multicentre rater blind randomised controlled trial to evaluate the clinical and cost-effectiveness of YCMAP including a sample of 652 participants, aged 12–18 years, presenting to general physicians/clinicians, emergency room after self harm or self referrals. We will test the effectiveness of 8–10 individual sessions of YCMAP delivered over 3 months compared with treatment as usual. Primary outcome measure is repetition of self-harm at 12 months. The seconday outcomes include reduction in suicidal ideation, hopelessness and distress and improvement in health related quality of life. Assessments will be completed at baseline, 3, 6, 9 and 12 months postrandomisation. The nested qualitative component will explore perceptions about management of self-harm and suicide prevention among adolescents and investigate participants’ experiences with YCMAP. The study will be guided by the theory of change approach to ensure that the whole trial is centred around needs of the end beneficiaries as key stakeholders in the process.Ethics and dissemination Ethics approval has been obtained from the Ethics Committee of University of Manchester, the National Bioethics Committee in Pakistan. The findings of this study will be disseminated through community workshops, social media, conference presentations and peer-reviewed journals.Trial registration number NCT04131179.

Purpose: MR-linacs (MRLs) have enabled the use of stereotactic magnetic resonance (MR) guided online adaptive radiotherapy (SMART) across many cancers. As data emerges to support SMART, uncertainty remains regarding optimal technical parameters, such as optimal patient positioning, immobilization, image quality, and contouring protocols. Prior to clinical implementation of SMART, we conducted a prospective study in healthy volunteers (HVs) to determine optimal technical parameters and to develop and practice a multidisciplinary SMART workflow. Methods: HVs 18 years or older were eligible to participate in this IRB-approved study. Using a 0.35 T MRL, simulated adaptive treatments were performed by a multi-disciplinary treatment team in HVs. For each scan, image quality parameters were assessed on a 5-point scale (5 = extremely high, 1 = extremely poor). Adaptive recontouring times were compared between HVs and subsequent clinical cases with a t-test. Results: 18 simulated treatments were performed in HVs on MRL. Mean parameters for visibility of target, visibility of nearby organs, and overall image quality were 4.58, 4.62, and 4.62, respectively (range of 4–5 for all measures). In HVs, mean ART was 15.7 min (range 4–35), comparable to mean of 16.1 (range 7–33) in the clinical cases (p = 0.8963). Using HV cases, optimal simulation and contouring guidelines were developed across a range of disease sites and have since been implemented clinically. Conclusions: Prior to clinical implementation of SMART, scans of HVs on an MRL resulted in acceptable image quality and target visibility across a range of organs with similar ARTs to clinical SMART. We continue to utilize HV scans prior to clinical implementation of SMART in new disease sites and to further optimize target tracking and immobilization. Further study is needed to determine the optimal duration of HV scanning prior to clinical implementation.

Infection of rat pulmonary microvascular endothelial cells with the bacterium Pseudomonas aeruginosa induces the production and release of cytotoxic oligomeric tau and beta amyloid (Aβ). Here, we characterized these cytotoxic amyloids. Cytotoxic behavior and oligomeric tau were partially resistant to digestion with proteinase K, but cytotoxicity was abolished by various denaturants including phenol, diethylpyrocarbonate (DEPC), and 1,1,1,3,3,3‐hexafluoro‐2‐isopropanol (HFIP). Ultracentrifugation for 8 h at 150 000 g was required to remove cytotoxic activity from the supernatant. Ultracentrifugation, DEPC treatment, and immunodepletion using antibodies against Aβ also demonstrated that cytoprotective protein(s) are released from endothelial cells during P. aeruginosa infection. Mass spectrometry of endothelial cell culture media following P. aeruginosa infection allowed identification of multiple potential secreted modulators of Aβ, including cystatin C, gelsolin, and ApoJ/clusterin. Immunodepletion, co‐immunoprecipitation, and ultracentrifugation determined that the cytoprotective factor released during infection of endothelial cells by P. aeruginosa is cystatin C, which appears to be in a complex with Aβ. Cytoprotective cystatin C may provide a novel therapeutic avenue for protection against the long‐term consequences of infection with P. aeruginosa.

Background The scoring rubric on the USMLE Step 1 examination will be changing to pass/fail in January 2022. This study elicits internal medicine resident perspectives on USMLE pass/fail scoring at the national level. Objective To assess internal medicine resident opinions regarding USMLE pass/fail scoring and examine how variables such as gender, scores on USMLE 1 and 2, PGY status and type of medical school are associated with these results. Methods In the fall of 2019, the authors surveyed current internal medicine residents via an on-line tool distributed through their program directors. Respondents indicated their Step 1 and Step 2 Clinical Knowledge scores from five categorical ranges. Questions on medical school type, year of training year, and gender were included. The results were analyzed utilizing Pearson Chi-square testing and multivariable logistic regression. Results 4012 residents responded, reflecting 13% of internal medicine residents currently training in the USA. Fifty-five percent of respondents disagreed/strongly disagreed with pass/fail scoring and 34% agreed/strongly agreed. Group-based differences were significant for gender, PGY level, Step 1 score, and medical school type; a higher percentage of males, those training at the PGY1 level, and graduates of international medical schools (IMGs) disagreed with pass/fail reporting. In addition, high scorers on Step 1 were more likely to disagree with pass/fail reporting than low scoring residents Conclusion Our results suggest that a majority of internal medicine residents, currently training in the USA prefer that USMLE numerical scoring is retained and not changed to pass/fail.

The internationalisation of higher education leads to benefits for students and universities. Part of the internationalisation process is student mobility through study abroad programmes such as Erasmus. This paper reflects on the study abroad process and experience for three Czech social pedagogy students from the faculty of education at Masaryk University in Brno, Czech Republic. The results of this small-scale study, collected through a questionnaire and a follow-up interview, showed that the study participants had similar motivations and experiences despite the different host institutions and study programmes. Furthermore, care needs to be taken when selecting a host university programme and ensuring that there are straightforward activities instructors can make use of to better prepare outgoing students. These findings lead to suggestions for classroom teachers as to how they can, to some degree, 'internationalise' their lessons, and how universities can encourage more students to take part in study abroad programmes, and to questions for future research.

BackgroundDepression is a common mental health problem with significant personal and social consequences. Studies have suggested that cognitive behavioral therapy (CBT) is an effective treatment for depression and anxiety when delivered one-to-one by an expert practitioner, but access to this talking therapy is often limited, and waiting lists can be long. However, a range of low-intensity interventions that can increase access to services are available including guided CBT self-help materials delivered via books, classes, and online packages. ObjectiveThis project aimed to pilot a randomized controlled trial (RCT) of an online CBT-based life skills course with community-based individuals experiencing depression. MethodsIndividuals with symptoms of depression were recruited directly from the community via newspaper advertisements. Participants were remotely randomized to receive either immediate access (IA) or delayed access (DA) to a research version of the Living Life to the Full online CBT-based life skills package (3rd edition) with telephone support provided by nonspecialist, charity-based workers while they used the online intervention. The primary end point was at 3 months postrandomization, at which point, the DA group were offered the intervention. Levels of depression, anxiety, social functioning, and satisfaction were assessed. ResultsThere were effective recruitment, randomization, and uptake, with 19 IA and 17 DA control participants entering the pilot study via newspaper advertisements and 13 of the 19 participants taking up the intervention. Overall, 72% (26/36) were not currently under the care of their general practitioner. The online package was acceptable to participants; the mean satisfaction score on the Client Satisfaction Questionnaire was 21 out of 32 (SD 8.89). At 3 months, data collection was achieved from 78% (28/36) of the participants. The efficacy and retention data were used for a power calculation indicating that 72 participants in total will be required for a future substantive RCT. ConclusionsThe research design successfully tested the recruitment, data collection, and intervention delivery. The pilot study has provided data for the required sample size for the full RCT. Trial RegistrationISRCTN registry ISRCTN12890709; https://doi.org/10.1186/ISRCTN12890709 International Registered Report Identifier (IRRID)RR2-10.1186/s13063-016-1336-y

Vaccination programs against COVID-19 vary globally with estimates of vaccine effectiveness (VE) affected by vaccine type, schedule, strain, outcome, and recipient characteristics. This study assessed VE of BNT162b2 and ChAdOx1 vaccines against PCR positive SARS-CoV-2 infection, hospital admission, and death among adults aged 50 years and older in Wales, UK during the period 7 December 2020 to 18 July 2021, when Alpha, followed by Delta, were the predominant variants. We used individual-level linked routinely collected data within the Secure Anonymized Information Linkage (SAIL) Databank. Data were available for 1,262,689 adults aged 50 years and over; coverage of one dose of any COVID-19 vaccine in this population was 92.6%, with coverage of two doses 90.4%. VE against PCR positive infection at 28-days or more post first dose of any COVID-19 vaccine was 16.0% (95%CI 9.6–22.0), and 42.0% (95%CI 36.5–47.1) seven or more days after a second dose. VE against hospital admission was higher at 72.9% (95%CI 63.6–79.8) 28 days or more post vaccination with one dose of any vaccine type, and 84.9% (95%CI 78.2–89.5) at 7 or more days post two doses. VE for one dose against death was estimated to be 80.9% (95%CI 72.1–86.9). VE against PCR positive infection and hospital admission was higher for BNT162b2 compared to ChAdOx1. In conclusion, vaccine uptake has been high among adults in Wales and VE estimates are encouraging, with two doses providing considerable protection against severe outcomes. Continued roll-out of the vaccination programme within Wales, and globally, is crucial in our fight against COVID-19.

Background: Organising health-care services for residents living in care homes is an important area of development in the UK and elsewhere. Medical care is provided by general practitioners in the UK, and the unique arrangement of the NHS means that general practitioners are also gatekeepers to other health services. Despite recent focus on improving health care for residents, there is a lack of knowledge about the role of general practitioners. Objectives: First, to review reports of research and quality improvement (or similar change management) in care homes to explore how general practitioners have been involved. Second, to develop programme theories explaining the role of general practitioners in improvement initiatives and outcomes. Design: A realist review was selected to address the complexity of integration of general practice and care homes. Setting: Care homes for older people in the UK, including residential and nursing homes. Participants: The focus of the literature review was the general practitioner, along with care home staff and other members of multidisciplinary teams. Alongside the literature, we interviewed general practitioners and held consultations with a Context Expert Group, including a care home representative. Interventions: The primary search did not specify interventions, but captured the range of interventions reported. Secondary searches focused on medication review and end-of-life care because these interventions have described general practitioner involvement. Outcomes: We sought to capture processes or indicators of good-quality care. Data sources: Sources were academic databases [including MEDLINE, EMBASE™ (Elsevier, Amsterdam, the Netherlands), Cumulative Index to Nursing and Allied Health Literature, PsycInfo® (American Psychological Association, Washington, DC, USA), Web of Science™ (Clarivate Analytics, Philadelphia, PA, USA) and Cochrane Collaboration] and grey literature using Google Scholar (Google Inc., Mountain View, CA, USA). Methods: Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) guidelines were followed, comprising literature scoping, interviews with general practitioners, iterative searches of academic databases and grey literature, and synthesis and development of overarching programme theories. Results: Scoping indicated the distinctiveness of the health and care system in UK and, because quality improvement is context dependent, we decided to focus on UK studies because of potential problems in synthesising across diverse systems. Searches identified 73 articles, of which 43 were excluded. To summarise analysis, programme theory 1 was ‘negotiated working with general practitioners’ where other members of the multidisciplinary team led initiatives and general practitioners provided support with the parts of improvement where their skills as primary care doctors were specifically required. Negotiation enabled matching of the diverse ways of working of general practitioners with diverse care home organisations. We found evidence that this could result in improvements in prescribing and end-of-life care for residents. Programme theory 2 included national or regional programmes that included clearly specified roles for general practitioners. This provided clarity of expectation, but the role that general practitioners actually played in delivery was not clear. Limitations: One reviewer screened all search results, but two reviewers conducted selection and data extraction steps. Conclusions: If local quality improvement initiatives were flexible, then they could be used to negotiate to build a trusting relationship with general practitioners, with evidence from specific examples, and this could improve prescribing and end-of-life care for residents. Larger improvement programmes aimed to define working patterns and build suitable capacity in care homes, but there was little evidence about the extent of local general practitioner involvement. Future work: Future work should describe the specific role, capacity and expertise of general practitioners, as well as the diversity of relationships between general practitioners and care homes. Study registration: This study is registered as PROSPERO CRD42019137090. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 9, No. 20. See the NIHR Journals Library website for further project information.

Introduction: YouTube is a popular website where public can access and gain information from videos related to COVID-19. This paper seeks to assess the quality and validity of information available on YouTube, based on the current Center for Disease Control (CDC) and World Health Organization (WHO) guidelines. Methods: We identified the 250 most-viewed videos from 1 January 2020 to 12 May 2020 on YouTube using keyword ‘COVID 19’. Two independent reviewers analyzed the English-language videos as useful, misleading, or news updates. Result: After excluding non-English and irrelevant videos, 100 videos were analyzed. Forty-four videos were classified as useful, 33 videos were classified as news updates, and 23 videos were classified as misleading. Independent users had five times increased odds of posting misleading videos (40% vs. 12%, OR = 5.05, 95% CI = 1.84–13.9, P = 0.001), whereas news agencies have 2.8 greater odds of posting useful or update videos (87% vs 44%, OR = 2.85, 95% CI = 0.959–8.45, P = 0.087). Conclusion: YouTube is an increasingly important source of medical information during the COVID-19 pandemic. Most of the videos were useful, however due to the public nature of the platform, misleading information may also be easily disseminated. Independent users are more likely to post-misleading videos.

Socially and economically disadvantaged racial and ethnic minorities have experienced comparatively severe clinical outcomes from the coronavirus disease (COVID-19) pandemic in the United States. Disparities in health outcomes arise from a myriad of synergistic biomedical and societal factors. Syndemic theory provides a useful framework for examining COVID-19 and other diseases that disproportionately affect vulnerable populations. Syndemic models ground research inquiries beyond individual clinical data to include non-biological community-based drivers of SARS-CoV-2 infection risk and severity of disease. Given the importance of such economic, environmental, and sociopolitical drivers in COVID-19, our aim in this Perspective is to examine entrenched racial and ethnic health inequalities and the magnitude of associated disease burdens, economic disenfranchisement, healthcare barriers, and hostile sociopolitical contexts—all salient syndemic factors brought into focus by the pandemic. Systemic racism persists within long-term care, health financing, and clinical care environments. We present proximal and distal public policy strategies that may mitigate the impact of this and future pandemics.

Objective To identify ethnic differences in proportion positive for SARS-CoV-2, and proportion hospitalised, proportion admitted to intensive care and proportion died in hospital with COVID-19 during the first epidemic wave in Wales.Design Descriptive analysis of 76 503 SARS-CoV-2 tests carried out in Wales to 31 May 2020. Cohort study of 4046 individuals hospitalised with confirmed COVID-19 between 1 March and 31 May. In both analyses, ethnicity was assigned using a name-based classifier.Setting Wales (UK).Primary and secondary outcomes Admission to an intensive care unit following hospitalisation with a positive SARS-CoV-2 PCR test. Death within 28 days of a positive SARS-CoV-2 PCR test.Results Using a name-based ethnicity classifier, we found a higher proportion of black, Asian and ethnic minority people tested for SARS-CoV-2 by PCR tested positive, compared with those classified as white. Hospitalised black, Asian and minority ethnic cases were younger (median age 53 compared with 76 years; p

This study examined whether scores on indices related to subclinical delusion formation and thinking style varied as a function of level of self-professed paranormal ability. To assess this, the researchers compared three groups differing in personal ascription of paranormal powers: no ability, self-professed ability, and paranormal practitioners (i.e., Mediums, Psychics, Spiritualists, and Fortune-Tellers). Paranormal practitioners (compared with no and self-professed ability conditions) were expected to score higher on paranormal belief, proneness to reality testing deficits, emotion-based reasoning, and lower on belief in science. Comparable differences were predicted between the self-professed and no ability conditions. A sample of 917 respondents (329 males, 588 females) completed self-report measures online. Multivariate analysis of variance (MANOVA) revealed an overall main effect. Further investigation, using discriminant descriptive analysis, indicated that paranormal practitioners scored higher on proneness to reality testing deficits, paranormal belief, and emotion-based reasoning. Belief in science did not meaningfully contribute to the discriminant function. Overall, results were consistent with previous academic work in the domains of paranormal belief and experience, which has reported that paranormal-related cognitions and perceptions are associated with factors related to subclinical delusion formation (i.e., emotion-based/intuitive thinking).

This study examined the degree to which within-individual variations in paranormal experience were related to belief in the paranormal, preferential thinking style, and delusion formation. A sample of 956 non-clinical adults completed measures assessing experience-based paranormal indices (i.e., paranormal experience, paranormal practitioner visiting, and paranormal ability), paranormal belief, belief in science, proneness to reality testing deficits, and emotion-based reasoning. Latent profile analysis (LPA) combined the experience-based indices to produce six underlying groups. Inter-class comparison via multivariate analysis of variance (MANOVA) indicated that both breadth and intensity of experiential factors were associated with higher belief in in the paranormal, increased proneness to reality testing deficits, and greater emotion-based reasoning. Belief in science, however, was less susceptible to experiential variations. Further analysis of reality testing subscales revealed that experiential profiles influenced levels of intrapsychic activity in subtle and intricate ways, especially those indexing Auditory and Visual Hallucinations and Delusional Thinking. Collectively, identification of profiles and inter-class comparisons provided a sophisticated understanding of the relative contribution of experiential factors to differences in paranormal belief, belief in science, proneness to reality testing deficits, and emotion-based reasoning.

Key message Complete lung collapse associated with sarcoidosis is exceedingly rare. Although lymphoma should be ruled out when patients with mediastinal lymphadenopathy develop lung collapse, sarcoidosis should be considered in the differential, especially when associated with fibrosing mediastinitis.

Background: Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). The surveillance describes the epidemiology and clinical characteristics of PIMS-TS in the United Kingdom and Ireland. Methods: Public Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit. Paediatricians were contacted monthly to report PIMS-TS, KD and TSS cases electronically and complete a detailed clinical questionnaire. Cases with symptom onset between 01 March and 15 June 2020 were included. Findings: There were 216 cases with features of PIMS-TS alone, 13 with features of both PIMS-TS and KD, 28 with features of PIMS-TS and TSS and 11 with features of PIMS-TS, KD and TSS, with differences in age, ethnicity, clinical presentation and disease severity between the phenotypic groups. There was a strong geographical and temporal association between SARS-CoV-2 infection rates and PIMS-TS cases. Of those tested, 14.8% (39/264) children had a positive SARS-CoV-2 RT-PCR, and 63.6% (75/118) were positive for SARS-CoV-2 antibodies. In total 44·0% (118/268) required intensive care, which was more common in cases with a TSS phenotype. Three of five children with cardiac arrest had TSS phenotype. Three children (1·1%) died. Interpretation: The strong association between SARS-CoV-2 infection and PIMS-TS emphasises the importance of maintaining low community infection rates to reduce the risk of this rare but severe complication in children and adolescents. Close follow-up will be important to monitor long-term complications in children with PIMS-TS. Funding: PHE.

Abnormal excitability in cortical networks has been reported in patients and animal models of Alzheimer's disease (AD), and other neurodegenerative conditions. Whether hyperexcitability is a core feature of alpha(α)-synucleinopathies, including dementia with Lewy bodies (DLB) is unclear. To assess this, we used two murine models of DLB that express either human mutant α-synuclein (α-syn) the hA30P, or human wild-type α-syn (hWT-α-syn) mice. We observed network hyperexcitability in vitro in young (2–5 months), pre-symptomatic transgenic α-syn mice. Interictal discharges (IIDs) were seen in the extracellular local field potential (LFP) in the hippocampus in hA30P and hWT-α-syn mice following kainate application, while only gamma frequency oscillations occurred in control mice. In addition, the concentration of the GABAA receptor antagonist (gabazine) needed to evoke IIDs was lower in slices from hA30P mice compared to control mice. hA30P mice also showed increased locomotor activity in the open field test compared to control mice. Intracellular recordings from CA3 pyramidal cells showed a more depolarised resting membrane potential in hA30P mice. Quadruple immunohistochemistry for human α-syn, and the mitochondrial markers, porin and the complex IV enzyme cytochrome c oxidase subunit 1 (COX1) in parvalbumin (PV+)-expressing interneurons showed that 25% of PV+ cells contained human α-syn in hA30P mice. While there was no change in PV expression, COX1 expression was significantly increased in PV+ cells in hA30P mice, perhaps reflecting a compensatory change to support PV+ interneuron activity. Our findings suggest that hippocampal network hyperexcitability may be an important early consequence of α-syn-mediated impairment of neuronal/synaptic function, which occurs without any overt loss of PV interneurons. The therapeutic benefit of targeting network excitability early in the disease stage should be explored with respect to α-synucleinopathies such as DLB.

African sleeping sickness is caused by Trypanosoma brucei, a parasite transmitted by the bite of a tsetse fly. Trypanosome infection induces a severe transcriptional downregulation of tsetse genes encoding for salivary proteins, which reduces its anti-hemostatic and anti-clotting properties. To better understand trypanosome transmission and the possible role of glycans in insect bloodfeeding, we characterized the N-glycome of tsetse saliva glycoproteins. Tsetse salivary N-glycans were enzymatically released, tagged with either 2-aminobenzamide (2-AB) or procainamide, and analyzed by HILIC-UHPLC-FLR coupled online with positive-ion ESI-LC-MS/MS. We found that the N-glycan profiles of T. brucei-infected and naïve tsetse salivary glycoproteins are almost identical, consisting mainly (>50%) of highly processed Man3GlcNAc2 in addition to several other paucimannose, high mannose, and few hybrid-type N-glycans. In overlay assays, these sugars were differentially recognized by the mannose receptor and DC-SIGN C-type lectins. We also show that salivary glycoproteins bind strongly to the surface of transmissible metacyclic trypanosomes. We suggest that although the repertoire of tsetse salivary N-glycans does not change during a trypanosome infection, the interactions with mannosylated glycoproteins may influence parasite transmission into the vertebrate host.

To mitigate the trade-off between gain and bandwidth of CMOS multistage amplifiers, a receiver front-end (FE) that employs a high-gain narrowband transimpedance amplifier (TIA) followed by an equalizing main amplifier (EMA) is proposed. The EMA provides a high-frequency peaking to extend the FE’s bandwidth from 25% to 60% of the targeted data rate fbit. The peaking is realized by adding a pole in the feedback paths of an active feedback-based wideband amplifier. By embedding the peaking in the main amplifier (MA), the front-end meets the sensitivity and gain of conventional equalizer-based receivers with better energy efficiency by eliminating the equalizer stages. Simulated in TSMC 65 nm CMOS technology, the proposed front-end achieves 7.4 dB and 6 dB higher gain at 10 Gb/s and 20 Gb/s, respectively, compared to a conventional front-end that is designed for equal bandwidth and dissipates the same power. The higher gain demonstrates the capability of the proposed technique in breaking the gain-bandwidth trade-off. The higher gain also reduces the power penalty incurred by the decision circuit and improves the sensitivity by 1.5 dB and 2.24 dB at 10 Gb/s and 20 Gb/s, respectively. Simulations also confirm that the proposed FE exhibits a robust performance against process and temperature variations and can support large input currents.

The Jizhong depression contains several geothermal reservoirs that are characterized by localized low-velocity anomalies. In this article, full-waveform inversion (FWI) is used to characterize these anomalies and determine their extent. This is a challenging problem because the reservoirs are quite small and the available data have usable frequencies only down to 5 Hz. An accurate-enough starting model is carefully built by using an iterative travel time tomography method combined with a cycle-skipping assessment method to begin the inversion at 5 Hz. A multiscale Laplace–Fourier-domain FWI with a layer-stripping approach is implemented on the starting model by gradually increasing the maximum offset. The result of overlapping the recovered velocity model on the migrated seismic profile shows a good correlation between the two results. The recovered model is assessed by ray tracing, synthetic seismogram modeling, checkerboard testing and comparisons with nearby borehole data. These tests indicate that low-velocity anomalies down to a size of 0.3 km × 0.3 km at a maximum depth of 2 km can be recovered. Combined with the well log data, the resulting velocity model allows us to delineate two potential geothermal resources, one of which was previously unknown.