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Abstract Background This study examined the association between menopausal symptoms and job satisfaction, and ascertained whether three psychosomatic factors (e.g., anxiety, depression, and sleep quality) interact with menopausal symptoms on job satisfaction. Methods A cross-sectional design with sensitivity analysis was adopted. The participants of the study were clinical health workers in England. Data from 154 health workers were analyzed with the hierarchical linear regression (HLR) analysis. Results There was a negative association between menopausal symptoms and job satisfaction (β = −0.38; t = −4.81, p 0.05) but was strengthened by anxiety (β = −0.22; t = −2.28; p

BackgroundThe APPROACH pilot study explored the feasibility and acceptability of an app (NHS Active 10) with brief, habit-based, behavioral support calls and print materials intended to increase brisk walking in people diagnosed with cancer. ObjectiveFollowing UK Medical Research Council guidelines, this study assessed the implementation of the intervention, examined the mechanisms of impact, and identified contextual factors influencing engagement. MethodsAdults (aged ≥18 y) with breast, prostate, or colorectal cancer who reported not meeting the UK guidelines for moderate-to-vigorous physical activity (≥150 min/wk) were recruited from a single hospital site in Yorkshire, United Kingdom. They were randomly assigned to the intervention or control (usual care) arm and assessed via quantitative surveys at baseline (time point 0 [T0]) and 3-month follow-up (time point 1 [T1]) and qualitative exit interviews (36/44, 82%) at T1. The process evaluation included intervention participants only (n=44). Implementation was assessed using data from the T1 questionnaire exploring the use of the intervention components. The perceived usefulness of the app, leaflet, and behavioral support call was rated from 0 to 5. Behavioral support calls were recorded, and the fidelity of delivery of 25 planned behavior change techniques was rated from 0 to 5 using an adapted Dreyfus scale. Mechanisms of impact were identified by examining T0 and T1 scores on the Self-Reported Behavioural Automaticity Index and feedback on the leaflet, app, call, and planner in the T1 questionnaire and qualitative interviews. Contextual factors influencing engagement were identified through qualitative interviews. ResultsThe implementation of the intervention was successful: 98% (43/44) of the participants received a behavioral support call, 78% (32/41) reported reading the leaflet, 95% (39/41) reported downloading the app, and 83% (34/41) reported using the planners. The mean perceived usefulness of the app was 4.3 (SD 0.8) in participants still using the app at T1 (n=33). Participants rated the leaflet (mean 3.9, SD 0.6) and the behavioral support call (mean 4.1, SD 1) as useful. The intended behavior change techniques in the behavioral support calls were proficiently delivered (overall mean 4.2, SD 1.2). Mechanisms of impact included habit formation, behavioral monitoring, and support and reassurance from the intervention facilitator. Contextual factors impacting engagement included barriers, such as the impact of cancer and its treatment, and facilitators, such as social support. ConclusionsThe APPROACH intervention was successfully implemented and shows promise for increasing brisk walking, potentially through promoting habit formation and enabling self-monitoring. Contextual factors will be important to consider when interpreting outcomes in the larger APPROACH randomized controlled trial. International Registered Report Identifier (IRRID)RR2-10.1186/s40814-022-01028-w

Purpose Lesbian, gay, bisexual, transgender, queer, and other sexual and gender diverse (LGBTQ+) individuals have health needs specific to their identities. However, they face discrimination and cis-heteronormativity in most patient-provider interactions, which often translate into poor healthcare. Evidence suggests doctors are inadequately trained to care for LGBTQ+ patients. Medical students are well-placed as the future workforce to establish affirming behaviours. This study garners LGBTQ+ patients’ healthcare experiences, where limited qualitative evidence exists, and explores whether students have insight into these experiences.Method Thirty LGBTQ+ patients and twenty students, evenly divided between Singapore and the United Kingdom (UK), two legally and culturally different countries, consented to semi-structured interviews in 2022 to evaluate their LGBTQ+ healthcare perceptions. Thematic analysis was conducted using a collaborative, iterative process involving five investigators, with frequent auditing of data interpretation.Results Most patients described implicit biases with a lack of support and professionalism from doctors, hindering health outcomes. Patients experienced misgendering and a lack of recognition of sexual and gender diversity; students appreciated the need to acknowledge patient identity. Although perceptions surrounding certain themes were similar between patients and students in both countries, patients’ voices on the complexity and dissatisfaction of gender-diverse care contrasted with students’ lack of insight on these themes. Singapore patients were more concerned with sociolegal acceptance affecting health needs, whilst UK patients noted more nuanced barriers to healthcare. Although many students were unsure about specific health needs and perceived a lack of training, they expressed willingness to create an equitable healthcare environment.Conclusions LGBTQ+ patients provided powerful narratives on discrimination surrounding their healthcare needs. To address these, medical students must be encouraged by healthcare educators to develop identity-affirming behaviours as future change-makers and challenge cis-heteronormative views. Alongside vital institutional changes tailored to each country, patients’ and students’ collective action would create meaningful educational opportunities to reach culture change.

Background: Sore throat is a common presentation in primary care. Approximately 15 % of sore throat in adults are caused by Group A Streptococcus (GAS). Clinical guidelines for sore throat recommend prescribing antibiotics only when there is a high probability that the condition has been caused by GAS. Most guidelines incorporate clinical prediction rules (CPRs) such as the Centor Score. Objectives: To present the prevalence and management of sore throat in young adults, with a particular focus on sore throat caused by GAS, including antibiotic prescribing and the retrospective application of the Centor Score. Methods: This prospective observational cohort study included 348 young adults with sore throat presenting in student health centres between 2017 and 2019. A descriptive overview of symptoms in participants with and without GAS is presented, and potential associations between participant characteristics and symptoms and antibiotic prescription were explored using regression analysis. The Centor Score was retrospectively calculated and explored. Results: 23 % (80) of participants had a positive throat swab for GAS. 65 % (225/345) of all participants were prescribed immediate and 12 % (43/345) delayed antibiotics. The symptoms and clinical signs most associated with antibiotic prescribing were exudate on tonsils, absence of cough and enlarged or tender anterior cervical lymph nodes. A retrospective analysis of the Centor score was possible for 337 participants of whom 49 % had a low (score ≤ 2) and 48 % a high Centor score (>2). For 50 % of participants, prescribing was in line with National Institute for Clinical Excellence (NICE) clinical guidelines, i.e. a Centor score of 3 or 4. Conclusions: Overall, the prevalence of GAS (23 %) was higher than the predicted 15 % for this population. Antibiotic prescribing was high. As the recommended maximum level of antibiotic prescribing is 20 % for sore throat, this presents an opportunity for improvement. A potential strategy could combine high Centor scores with point of care testing.

Abstract Background A cancer diagnosis and its treatment may be an especially isolating experience. Despite evidence that positive health behaviours can improve outcomes for people living with and beyond cancer (LWBC), no studies have examined associations between loneliness and different health behaviours in this population. This study aimed to describe the prevalence of loneliness in a large sample of UK adults LWBC and to explore whether loneliness was associated with multiple health behaviours. Methods Participants were adults (aged ≥ 18 years) diagnosed with breast, prostate or colorectal cancer who completed the Health and Lifestyle After Cancer Survey. Loneliness was reported using the UCLA loneliness score, dichotomised into higher (≥ 6) versus lower (

Abstract Background Despite shifting global attitudes, mental illness remains highly stigmatised amongst practicing doctors. This has wider implications on doctors’ training to care for patients with mental illness. There is need for exploration of the presence and mitigation of stigma in early medical education to prevent such attitudes propagating into clinical practice. Thus, this study explores whether stigmatising attitudes are detectable amongst medical students in London and Singapore and examines whether they are ameliorated by specific curricular and welfare features of formal medical education, utilising the Mental Illness Stigma Framework (MISF). Methods A mixed-methods approach was adopted. Medical students at Imperial College London (UK; n = 211) and Nanyang Technological University (Singapore; n = 141) completed a validated scale (the OMS-HC-15) to assess attitudes towards mental illness. Semi-structured interviews were conducted (Imperial: n = 12, NTU: n = 8) until theoretical saturation was reached. Quantitative data were analysed descriptively and comparatively using SPSS and interview data subjected to inductive thematic analysis. Results Total OMS-HC-15 scores ranged from 19–51 for Imperial (n = 211) and 16–53 for NTU (n = 141). No significant differences in overall stigma scores were found between the two schools (p = 0.24), nor when comparing year groups within each school. Four themes were identified across interview data: student perceptions, impacts of medical school culture, university support, and curricular impacts on mental illness perceptions. Themes allowed identification of aspects of medical school that were well-received and warranted further emphasis by students, alongside areas for improvement. Conclusion Mental health stigma was identified in two medical schools, with differing cultures. Mean stigma scores obtained were comparable between both UK and Singaporean medical students. Nuanced differences were identified via subgroup analysis, and the MISF identified both shared and country-specific drivers for this stigma across the qualitative data. Actionable recommendations to mitigate this were hypothesised. Curricular improvements such as earlier psychiatric teaching and sharing of personal stories may improve future stigma scores as students’ progress through the course. Specific welfare-based changes to formal support systems were also deemed to be beneficial by students. The impacts of welfare and curricular redesign in relation to societal influence on students’ attitudes warrants further investigation, as does medical students’ self-stigma.

Abstract Tankyrase 1 and 2 are ADP-ribosyltransferases that catalyze formation of polyADP-Ribose (PAR) onto themselves and their binding partners. Tankyrase protein levels are regulated by the PAR-binding E3 ligase RNF146, which promotes K48-linked polyubiquitylation and proteasomal degradation of tankyrase and its partners. We identified a novel interaction between tankyrase and a distinct class of E3 ligases: the RING-UIM (Ubiquitin-Interacting Motif) family. We show that RNF114 and RNF166 bind and stabilize monoubiquitylated tankyrase and promote K11-linked diubiquitylation. This action competes with RNF146-mediated degradation, leading to stabilization of tankyrase and its binding partner, Angiomotin, a cancer cell signaling protein. Moreover, we identify multiple PAR-binding E3 ligases that promote ubiquitylation of tankyrase and induce stabilization or degradation. Discovery of K11 ubiquitylation that opposes degradation, along with identification of multiple PAR-binding E3 ligases that ubiquitylate tankyrase, provide insights into mechanisms of tankyrase regulation and may offer additional uses for tankyrase inhibitors in cancer therapy.

Introduction Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM) is a research programme that seeks to develop and evaluate a comprehensive exercise-based rehabilitation intervention designed for people with multimorbidity, the presence of multiple long-term conditions (MLTCs). This paper describes the protocol for a randomised trial to assess the feasibility and acceptability of the PERFORM intervention, study design and processes.Methods and analysis A multicentre, parallel two-group randomised trial with individual 2:1 allocation to the PERFORM exercise-based intervention plus usual care (intervention) or usual care alone (control). The primary outcome of this feasibility trial will be to assess whether prespecified progression criteria (recruitment, retention, intervention adherence) are met to progress to the full randomised trial. The trial will be conducted across three UK sites and 60 people with MLTCs, defined as two or more LTCs, with at least one having evidence of the beneficial effect of exercise. The PERFORM intervention comprises an 8-week (twice a week for 6 weeks and once a week for 2 weeks) supervised rehabilitation programme of personalised exercise training and self-management education delivered by trained healthcare professionals followed by two maintenance sessions. Trial participants will be recruited over a 4.5-month period, and outcomes assessed at baseline (prerandomisation) and 3 months postrandomisation and include health-related quality of life, psychological well-being, symptom burden, frailty, exercise capacity, physical activity, sleep, cognition and serious adverse events. A mixed-methods process evaluation will assess acceptability, feasibility and fidelity of intervention delivery and feasibility of trial processes. An economic evaluation will assess the feasibility of data collection and estimate the costs of the PERFORM intervention.Ethics and dissemination The trial has been given favourable opinion by the West Midlands, Edgbaston Research Ethics Service (Ref: 23/WM/0057). Participants will be asked to give full, written consent to take part by trained researchers. Findings will be disseminated via journals, presentations and targeted communications to clinicians, commissioners, service users and patients and the public.Trial registration number ISRCTN68786622.Protocol version 2.0 (16 May 2023).

Abstract Introduction Increased moderate to vigorous physical activity (MVPA) can improve clinical and psychosocial outcomes for people living with and beyond cancer (LWBC). This study aimed to assess the feasibility and acceptability of trial procedures in a pilot randomised controlled trial (RCT) of a theory‐driven app‐based intervention with behavioural support focused on promoting brisk walking (a form of MVPA) in people LWBC (APPROACH). Methods Participants diagnosed with breast, prostate or colorectal cancer were recruited from a single UK hospital site. Assessments at baseline and 3 months included online questionnaires, device‐measured brisk walking (activPAL accelerometer) and self‐reported weight and height. Participants were randomised to intervention or control (care as usual). The intervention comprised a non‐cancer‐specific app to promote brisk walking (National Health Service ‘Active 10’) augmented with print information about habit formation, a walking planner and two behavioural support telephone calls. Feasibility and acceptability of trial procedures were explored. Initial estimates for physical activity informed a power calculation for a phase III RCT. A preliminary health economics analysis was conducted. Results Of those medically eligible, 369/577 (64%) were willing to answer further eligibility questions and 90/148 (61%) of those eligible were enrolled. Feasibility outcomes, including retention (97%), assessment completion rates (>86%) and app download rates in the intervention group (96%), suggest that the trial procedures are acceptable and that the intervention is feasible. The phase III RCT will require 472 participants to be randomised. As expected, the preliminary health economic analyses indicate a high level of uncertainty around the cost‐effectiveness of the intervention. Conclusions This pilot study demonstrates that a large trial of the brisk walking intervention with behavioural support is both feasible and acceptable to people LWBC. The results support progression onto a confirmatory phase III trial to determine the efficacy and cost‐effectiveness of the intervention.

Abstract Background Primary care and other health services have been disrupted during the COVID-19 pandemic, yet the consequences of these service disruptions on patients’ care experiences remain largely unstudied. People with mental-physical multimorbidity are vulnerable to the effects of the pandemic, and to sudden service disruptions. It is thus essential to better understand how their care experiences have been impacted by the current pandemic. This study aims to improve understanding of the care experiences of people with mental-physical multimorbidity during the pandemic and identify strategies to enhance these experiences. Methods We will conduct a mixed-methods study with multi-phase approach involving four distinct phases. Phase 1 will be a qualitative descriptive study in which we interview individuals with mental-physical multimorbidity and health professionals in order to explore the impacts of the pandemic on care experiences, as well as their perspectives on how care can be improved. The results of this phase will inform the design of study phases 2 and 3. Phase 2 will involve journey mapping exercises with a sub-group of participants with mental-physical multimorbidity to visually map out their care interactions and experiences over time and the critical moments that shaped their experiences. Phase 3 will involve an online, cross-sectional survey of care experiences administered to a larger group of people with mental disorders and/or chronic physical conditions. In phase 4, deliberative dialogues will be held with key partners to discuss and plan strategies for improving the delivery of care to people with mental-physical multimorbidity. Pre-dialogue workshops will enable us to synthesize an prepare the results from the previous three study phases. Discussion Our study results will generate much needed evidence of the positive and negative impacts of the COVID-19 pandemic on the care experiences of people with mental-physical multimorbidity and shed light on strategies that could improve care quality and experiences.

Abstract Background Many people living with and beyond cancer (LWBC) do not meet dietary recommendations. To implement a healthier diet, people LWBC must perceive a need to improve their diet. Methods Participants included people diagnosed with breast, prostate or colorectal cancer in the UK. Two binary logistic regression models were conducted with perceived need for dietary change as the outcome (need to improve vs. no need). Predictor variables included demographic and clinical characteristics, receipt of dietary advice, and either body mass index (BMI) or adherence to seven relevant World Cancer Research Fund (WCRF) dietary recommendations. Results The sample included 5835 responses. Only 31% perceived a need to improve their diet. Being younger (odds ratio [OR] 0.95, 95% confidence interval [CI] = 94–0.95), female (OR = 1.33, 95% CI = 1.15–1.53), not of white ethnicity (OR = 1.8, 95% CI = 1.48–2.27), not married/cohabiting (OR = 1.32, 95% CI = 1.16–1.52) and having received dietary advice (OR = 1.36, 95% CI = 1.43–1.86) was associated with an increased odds of perceiving a need to improve diet. This association was also seen for participants with two or more comorbidities (OR = 1.31, 95% CI = 1.09–1.57), those not meeting the recommendations for fruit and vegetables (OR = 0.47, 95% CI = 0.41–0.55), fat (OR = 0.67, 95% CI = 0.58–0.77), and sugar (OR = 0.86, 95% CI = 0.75–0.98) in the dietary components model and those who had a higher BMI (OR = 1.53, 95% CI = 1.32–1.77) in the BMI model. Conclusions Most of this sample of people LWBC did not perceive a need to improve their diet. More research is needed to understand the reasons for this and to target these reasons in dietary interventions.

Abstract Introduction Imperial College Teddy Bear Hospital (ICSM-TBH) is a student-led volunteering group, which uses interactive, play-based teaching to educate school pupils aged 5–7 years about healthy lifestyles and healthcare. During the COVID-19 pandemic, volunteering sessions shifted online. The aim of this study was to compare the value of online and in-person ICSM-TBH volunteering for volunteers and school pupils. Methods Undergraduate university students at Imperial College London (medicine can be taken as a first degree in the UK) who volunteered with ICSM-TBH between 2019 and 22 were invited to complete an anonymous online questionnaire evaluating their experiences of volunteering online and in-person through Likert-scale questions. Those who completed the questionnaire were also invited to an interview. Teachers who hosted online ICSM-TBH sessions were also invited to an in-person interview, exploring their view of their pupils’ experiences with these sessions. Questionnaire results were analysed through descriptive statistics. Interviews were analysed through inductive thematic analysis. Results Thirty-two university students completed the questionnaire. Of these, 9 experienced both in-person and online volunteering, all of whom preferred in-person volunteering. For those who only volunteered in-person, 92% reported that ICSM-TBH sessions were a positive experience, compared to 100% who volunteered online; 92% in person volunteers agreed or strongly agreed that ICSM-TBH volunteering in person improved their mood, compared to 89% online; and 100% agreed or strongly agreed that ICSM-TBH volunteering in person helped them feel part of a community, compared to 84% online. A total of 12 volunteers and 4 teachers were interviewed, from whom five themes emerged: interaction and engagement (interaction and engagement between pupils and volunteers was more readily achieved in-person); personal and professional development (both online and in-person sessions enabled volunteers to gain valuable skills); community and social (greater sense of community was established in-person); emotional wellbeing and enjoyment (both modalities were enjoyed by volunteers and pupils); and workload (online sessions were more convenient for volunteers but with risk of screen fatigue). Conclusion Overall, both in-person and online volunteering were of substantial benefit to volunteers and school pupils. However, most teachers and volunteers preferred in-person volunteering.

ObjectivesThis study aims to provide a comprehensive analysis of clinical and epidemiological data related to Chronic Chagas Cardiomyopathy (CCC) in the Amazon region of Brazil.MethodsA review of observational, retrospective, and cross-sectional studies related to Chagas Disease in the Amazon region of Brazil was conducted, and a case series addressing CCC in patients treated at the FMT-HVD outpatient clinic, a reference center for Chagas disease in Brazil, was carried out.ResultsClinical characteristics of 55 patients from the Amazon region with CCC were described. The most common electrocardiographic alteration observed was abnormal ventricular repolarization (AVR), present in 40% of cases. The most common echocardiographic finding was left ventricular systolic dysfunction (49%), followed by akinesia or hypokinesia of the inferior and/or inferolateral walls (38.1%) and the presence of an apical aneurysm (32.7%).ConclusionsOverall, this study demonstrates that CCC in the Amazon region presents clinical characteristics and severity that are similar to those observed in other regions. However, certain peculiarities, such as the frequency of right bundle branch block (RBBB) and anterior and septal involvement during the acute phase, require additional investigation to better comprehend the disease in the region. Overall, the study provides crucial clinical insights for the diagnosis and treatment of CCC in the Amazon region.

Summary: Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18–64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63–3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68–14.32) also satisfied the non-inferiority criterion (95% CI lower limit > −5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Summary: Resolution of cohesion between sister telomeres in human cells depends on TRF1-mediated recruitment of the polyADP-ribosyltransferase tankyrase to telomeres. In human aged cells, due to insufficient recruitment of TRF1/tankyrase to shortened telomeres, sisters remain cohered in mitosis. This persistent cohesion plays a protective role, but the mechanism by which sisters remain cohered is not well understood. Here we show that telomere repeat-containing RNA (TERRA) holds sister telomeres together through RNA-DNA hybrid (R-loop) structures. We show that a tankyrase-interacting partner, the RNA-binding protein C19orf43, is required for repression of TERRA R-loops. Persistent telomere cohesion in C19orf43-depleted cells is counteracted by RNaseH1, confirming that RNA-DNA hybrids hold sisters together. Consistent with a protective role for persistent telomere cohesion, depletion of C19orf43 in aged cells reduces DNA damage and delays replicative senescence. We propose that the inherent inability of shortened telomeres to recruit R-loop-repressing machinery permits a controlled onset of senescence.

IntroductionLesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) individuals have an increased scope of healthcare needs and face many barriers to accessing healthcare. However, LGBTQ+ healthcare education remains scarce, and students’ understanding of LGBTQ+ healthcare remains largely uncharacterised. This study investigated the knowledge of and attitudes toward LGBTQ+ healthcare among medical students in Singapore and the United Kingdom (UK), two culturally different countries.MethodsMedical students in two medical schools, one in Singapore and the other in the UK, completed self-administered cross-sectional surveys using multiple-choice, Likert scale, and free-text questions to explore their ideas, concerns, and expectations about LGBTQ+ healthcare education within their medical curricula.ResultsFrom 330 responses, students’ knowledge levels were moderate overall, with pronounced gaps in certain areas, including terminology, sexual health, and conversion therapy. Deficiencies in knowledge were significantly greater among students in Singapore compared to the UK (p

Introduction: The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence to decision (EtD) framework provides a structured and transparent approach for clinical guideline developers to use when formulating recommendations. Understanding how stakeholders use the EtD framework will inform how best to provide future training and support. This scoping review objective is to identify the key characteristics of how the GRADE EtD framework is used and identify studies on perception of use by those involved in developing clinical guidelines. Methods: JBI methodology for scoping reviews will be followed. This scoping review will consider both peer review published literature and grey literature. This will include empirical studies on the use of EtDs (including both quantitative, qualitative, and mixed methods primary research articles) and discussion papers/ commentaries on the experience of using the EtD. It will also include a random sample of publicly available populated EtDs identified from databases and repositories of GRADE guidelines. The search strategy will aim to locate both published and unpublished documents. First, we will conduct an exploratory search of MEDLINE and Embase (Elsevier), supplemented with citation analysis of included articles. Populated EtDs will be identified through searches of databases and repositories of GRADE guidelines. Two researchers will independently screen, select, and extract identified documents. Data will be presented in tables and summarized descriptively. Conclusion: This scoping review will identify the key characteristics of how the GRADE EtD framework is currently being used in clinical guidelines. Review findings can be used to inform future guidance and requirements for using GRADE EtD, as well as training on how to consider the criteria in developing recommendations. Results will be disseminated through publications in peer – reviewed journals and conference presentations. We will present our findings to relevant stakeholders via the networks of the co-author team at a one-day workshop.

Objective The prevalence of comorbid chronic kidney disease (CKD) and osteoarthritis (OA) is increasing globally. While sharing common risk factors, the mechanism and consequences of concurrent CKD-OA are unclear. The aims of the study were to develop a preclinical comorbid model, and to investigate the disease-modifying interactions.Methods Seventy (70) male 8–10 week-old C57BL/6 mice were subjected to 5/6 nephrectomy (5/6Nx)±destabilisation of medial meniscus (DMM) or sham surgery. OA pathology and CKD were assessed 12 weeks postinduction by blinded histology scoring, micro-CT, immunohistochemistry for osteoclast and matrix metalloproteinase (MMP)-13 activity, and serum analysis of bone metabolic markers.Results The 5/6Nx model recapitulated characteristic features of CKD, with renal fibrosis and deranged serum alkaline phosphatase, calcium and phosphate. There was no histological evidence of cartilage pathology induced by 5/6Nx alone, however, synovial MMP-13 expression and subchondral bone osteoclastic activity were increased (p

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic cause of adult T-cell leukemia/lymphoma (ATL) and encodes a viral oncoprotein (Hbz) that is consistently expressed in asymptomatic carriers and ATL patients, suggesting its importance in the development and maintenance of HTLV-1 leukemic cells. Our previous work found Hbz protein is dispensable for virus-mediated T-cell immortalization but enhances viral persistence. We and others have also shown that hbz mRNA promotes T-cell proliferation. In our current studies, we evaluated the role of hbz mRNA on HTLV-1-mediated immortalization in vitro as well as in vivo persistence and disease development. We generated mutant proviral clones to examine the individual contributions of hbz mRNA, hbz mRNA secondary structure (stem-loop), and Hbz protein. Wild-type (WT) and all mutant viruses produced virions and immortalized T-cells in vitro. Viral persistence and disease development were also evaluated in vivo by infection of a rabbit model and humanized immune system (HIS) mice, respectively. Proviral load and sense and antisense viral gene expression were significantly lower in rabbits infected with mutant viruses lacking Hbz protein compared to WT or virus with an altered hbz mRNA stem-loop (M3 mutant). HIS mice infected with Hbz protein-deficient viruses showed significantly increased survival times compared to animals infected with WT or M3 mutant virus. Altered hbz mRNA secondary structure, or loss of hbz mRNA or protein, has no significant effect on T-cell immortalization induced by HTLV-1 in vitro; however, the Hbz protein plays a critical role in establishing viral persistence and leukemogenesis in vivo.

Abstract Background Imperial College London launched a new, spiral undergraduate medical curriculum in September 2019. Clinical & Scientific Integrative cases (CSI) is an innovative, flagship module, which uses pioneering methodology to provide early-years learning that [1] is patient-centred, [2] integrates clinical and scientific curriculum content, [3] develops advanced team-work skills and [4] provides engaging, student-driven learning. These aims are designed to produce medical graduates equipped to excel in a modern healthcare environment. Methods CSI has adopted a novel educational approach which utilises contemporary digital resources to deliver a collaborative case-based learning (CBL) component, paired with a team-based learning (TBL) component that incorporates both learning and programmatic assessment. This paper serves to explore how first-year students experienced CSI in relation to its key aims, drawing upon quantitative and qualitative data from feedback surveys from CSI’s inaugural year. It provides a description and analysis of the module’s design, delivery, successes and challenges. Results Our findings indicate that CSI has been extremely well-received and that the majority of students agree that it met its aims. Survey outputs indicate success in integrating multiple elements of the curriculum, developing an early holistic approach towards patients, expediting the development of important team-working skills, and delivering authentic and challenging clinical problems, which our students found highly relevant. Challenges have included supporting students to adapt to a student-driven, deep learning approach. Conclusions First-year students appear to have adopted a patient-centred outlook, the ability to integrate knowledge from across the curriculum, an appreciation for other team members and the self-efficacy to collaboratively tackle challenging, authentic clinical problems. Ultimately, CSI’s innovative design is attractive and pertinent to the needs of modern medical students and ultimately, future doctors.

Objectives Infectious mononucleosis (IM) is a clinical syndrome that is characterised by lymphadenopathy, fever and sore throat. Although generally not considered a serious illness, IM can lead to significant loss of time from school or work due to profound fatigue, or the development of chronic illness. This study aimed to derive and externally validate clinical prediction rules (CPRs) for IM caused by Epstein-Barr virus (EBV).Design Prospective cohort study.Setting and participants 328 participants were recruited prospectively for the derivation cohort, from seven university-affiliated student health centres in Ireland. Participants were young adults (17–39 years old, mean age 20.6 years) with sore throat and one other additional symptom suggestive of IM. The validation cohort was a retrospective cohort of 1498 participants from a student health centre at the University of Georgia, USA.Main outcome measures Regression analyses were used to develop four CPR models, internally validated in the derivation cohort. External validation was carried out in the geographically separate validation cohort.Results In the derivation cohort, there were 328 participants, of whom 42 (12.8%) had a positive EBV serology test result. Of 1498 participants in the validation cohort, 243 (16.2%) had positive heterophile antibody tests for IM. Four alternative CPR models were developed and compared. There was moderate discrimination and good calibration for all models. The sparsest CPR included presence of enlarged/tender posterior cervical lymph nodes and presence of exudate on the pharynx. This model had moderate discrimination (area under the receiver operating characteristic curve (AUC): 0.70; 95% CI: 0.62–0.79) and good calibration. On external validation, this model demonstrated reasonable discrimination (AUC: 0.69; 95% CI: 0.67–0.72) and good calibration.Conclusions The alternative CPRs proposed can provide quantitative probability estimates of IM. Used in conjunction with serological testing for atypical lymphocytosis and immunoglobulin testing for viral capsid antigen, CPRs can enhance diagnostic decision-making for IM in community settings.

Understanding the emotions experienced by higher education instructors related to assessment feedback, how instructors understand student emotions, and how instructors might manage these emotions positively, can help to secure the educational benefits of feedback. In this research, we aimed to explore the emotional responses that instructors experienced through the giving and receiving of assessment feedback. We undertook qualitative data collection, carrying out individual semi-structured interviews with instructors from three universities who had administered a dialogic feed-forward intervention on one of their teaching units. The full interview transcripts were analysed inductively using thematic analysis. Five main themes emerged from the interview data: 1. Summative written feedback aroused largely negative emotions in instructors because they felt distanced from their students; 2. Instructors experienced a broad range of emotions related to dialogic feed-forward encounters, emerging from their proximity to students; 3. Dialogic feed-forward, as an affective encounter, was emotionally challenging for instructors; 4. Dialogic feed-forward built strong learning relationships between students and instructors, strengthening students’ sense of belonging; 5. Dialogic feed-forward was transformational for instructors as educators. We consider the implications of our findings for instructors and wider assessment and feedback practices, including emotional labour, promotional reward, and instructor professional development.

Employability is not just about focusing on building the students' workplace experience but about developing their social and cultural capital through learning. In higher education, the selected pedagogies are central to that development (Pegg, 2012). Thoughtful curricular design which maximises student engagement and adopts pedagogies for career and employability learning can help to prepare students for the reality of the workplace. These pedagogies with social connection at their heart can enhance student wellbeing and their perceived sense of belonging to their course and the wider world. This can thus build more confident, reflective, and collaborative graduates who should ultimately be more employable (Rowe, Jackson and Fleming, 2023). This paper uses a qualitative approach to outline four course-based case study examples of pedagogies that strengthen the behaviours and skills that enhance students' employability. The curricular and pedagogic practices of each are examined, and significant themes from each are then synthesised. Together they demonstrate how thoughtful course design and inclusive, integrated, contextualised pedagogic approaches support the development of students' employability learning and graduate skills (Healy, 2023). The common themes from the case studies focused on self-directed, student-centred, authentic learning which encouraged students to (i) work with industry and communities to build early professional networks, (ii) engage in connected learning where the curriculum and its supporting activities and pedagogy facilitate collaborative learning, and (iii) develop confidence, a sense of belonging and professional identities through using these inclusive, collaborative learning approaches. In addition, six practical pedagogic principles are identified for course teams to utilise. These include (i) focus on inclusive practice, (ii) building students' professional identity, (iii) developing students' belonging, (iv) deep critical thinking, (v) the demystification of the workplace through the activities selected, and (vi) students leading their own learning. This paper integrates a series of reflective questions (mapped to each principle) for educational developers to consider as they design future learning activities which foster graduate skills during career and employability learning.

The FRIENDS Resilience programs provide cognitive-behavioral skills across the developmental spectrum and can be applied as a universal or selective prevention program. In the current study, we assessed whether, relative to the schools' existing counseling curriculum ("guidance"), FRIENDS improved social skills, problem behaviors, and academic competence in a sample of 650 students in kindergarten, 2nd, 5th, and 7th grade in a rural community in the northeastern United States. Student, parent, and teacher reports were obtained pre-intervention, post-intervention, and 4 months later. Analyses examined FRIENDS as a universal prevention program in the general school population and as a selective intervention for at-risk students (those with elevated existing symptoms). Teachers reported improvements in social skills, problem behaviors, and academic competence, and parents reported improved problem behaviors immediately post-intervention for all students receiving FRIENDS and guidance. However, at-risk students who received FRIENDS experienced significantly greater improvements in teacher-reported problem behaviors compared to those who received guidance. When assessing changes over time once all students had received FRIENDS, teacher-rated social skills and academic competence improved, and student- and parent-rated problem behaviors decreased from pre- to post-FRIENDS and 4-month follow-up. Effects were consistent for the overall sample and at-risk students, with stronger effects for those at-risk. These small yet significant effects of FRIENDS as universal prevention may be more limited relative to usual guidance curriculum, but preventative effects may be enhanced for those students in more immediate need of support. Directions for future evaluation of FRIENDS are discussed.

Abstract Background In the Brazilian Amazon, a new epidemiological profile of Chagas disease transmission, the oral route, has been detected and cited as being responsible for the increase in acute cases in Brazil. The clinical evaluation of acute Chagas disease (ACD) has been a challenge since it can progress to a chronic phase with cardiac alterations, and the follow-up by modern diagnostic methods is very difficult due to the socio-geographical characteristics of the Brazilian Amazon. Thus, alternatives should be sought to alleviate this problem. We conducted a study to evaluate subjects with ACD using the 12-lead ECG QRS score (Selvester score) as an estimative of myocardial injury progression before and after ACD treatment. Methods The study included indigenous subjects from the Amazon region with ACD in clinical follow-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) Chagas Disease outpatient clinic in the state of Amazonas, Brazil. The control group consisted of 31 healthy volunteers with no history of heart disease and no reactive serology for Chagas disease. Baseline ECG was performed in all subjects. The Selvester scoring method was performed according to the standardized guide ( 3: points × 3% = % of the predicted LV infarction). Results A total of 62 subjects were included, 31 as cases and 31 as controls. The mean follow-up of the case group was 17 months. The control group presented normal ECG. The case group presented 13 alterations before treatment and 11 after. Nineteen individuals presented scores > 3 points, 6 before and 13 after. In 19.36% of subjects, myocardial injury was found before treatment and in 41.94% after treatment. Conclusion This is the first study that uses the Selvester score (SS) to predict myocardial injury in subjects with ACD. The results of this study suggest the significant presence of myocardial injury from the beginning of treatment to the period post treatment of ACD, which demonstrates that the SS can be applied for stratification and follow-up of Chagas disease in the Amazon region.

Human T-cell leukemia virus type 1 (HTLV-1) is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL) and chronic neurological disease. The disparity between silenced sense transcription versus constitutively active antisense (Hbz) transcription from the integrated provirus is not fully understood. The presence of an internal viral enhancer has recently been discovered in the Tax gene near the 3’ long terminal repeat (LTR) of HTLV-1. In vitro, this enhancer has been shown to bind SRF and ELK-1 host transcription factors, maintain chromatin openness and viral gene transcription, and induce aberrant host gene transcription near viral integration sites. However, the function of the viral enhancer in the context of early HTLV-1 infection events remains unknown. In this study, we generated a mutant Enhancer virus (mEnhancer) and evaluated its effects on HTLV-1-mediated in vitro immortalization, establishment of persistent infection with an in vivo rabbit model, and disease development in a humanized immune system (HIS) mouse model. The mEnhancer virus was able to establish persistent infection in rabbits, and there were no significant differences in proviral load or HTLV-1-specific antibody responses over a 25-week study. However, rabbits infected with the mEnhancer virus had significantly decreased sense and antisense viral gene expression at 12-weeks post-infection. HIS mice infected with wt or mEnhancer virus showed similar disease progression, proviral load, and viral gene expression. While mEnhancer virus was able to sufficiently immortalize primary T-lymphocytes in cell culture, the immortalized cells had an altered phenotype (CD8+ T-cells), decreased proviral load, decreased sense and anti-sense gene expression, and altered cell cycle progression compared to HTLV-1.wt immortalized cells (CD4+ T-cells). These results suggest that the HTLV-1 enhancer element alone does not determine persistence or disease development but plays a pivotal role in regulating viral gene expression.

Background Chagas disease is a neglected tropical disease that is still considered a global health emergency. In the Amazon region, most of the reports are of acute cases that are associated with oral transmission. This study aimed to evaluate myocardial injury in patients with acute Chagas disease before and after treatment. Methods and Results We evaluated 23 patients with acute Chagas disease in 3 different stages of progression. Group 1 had 12 patients evaluated during the acute phase, at the time of diagnosis, and 1 year after treatment, and Group 2 had 11 patients in the late postacute phase who were evaluated 5.2 years on average after diagnosis and treatment. ECGs with the Selvester score, 24‐hour Holter exam, and cardiovascular magnetic resonance imaging were performed. The mean age of the 23 patients was 44.3±18.9 years, and they were mostly men (15/65.24%) from Amazonas state (22/95.6%). In 69.6% (n=16) of the patients, some ECG alterations were found, the most frequent being left anterior fascicular block and ventricular repolarization. In Group 1, the 24‐hour Holter exam showed atrial tachycardia in 3 (25%) patients and ventricular extrasystoles in 2 (16.7%) patients. In Group 2, 1 patient had ventricular extrasystoles. Myocardial injury was observed in 7 patients (58.3%) at the acute phase and in 5 (50%) patients at the 1‐year follow‐up in Group 1 and in 2 (18.2%) patients in Group 2. Conclusions This article describes, for the first time, myocardial injury shown by cardiovascular magnetic resonance imaging in a group of patients with acute Chagas disease and reveals the importance of early detection and follow‐up of the cardiac impairment in these patients.

Objectives: To compare topical granulocyte and macrophage colony-stimulating factor (GM-CSF) and miltefosine (G + M) versus placebo and miltefosine (P + M) or parenteral meglumine antimoniate (MA) in the treatment of 150 patients with cutaneous leishmaniasis (CL) caused by Leishmania guyanensis in the Amazon. Design: A randomized and double-blinded clinical trial. Results: At 90 days after the initiation of therapy, the cure rates were 66%, 58%, and 52% for the groups P + M, G + M, and MA, respectively (p > 0.05). Cure rates at 180 days did not differ. Healing time was similar in the 3 groups, but faster in the MA group as compared to the G + M group (p = 0.04). Mild and transitory systemic adverse events were frequent in all groups (above 85%). Nausea (85%) and vomiting (39%) predominated in the miltefosine groups and arthralgia (51%) and myalgia (48%) in the MA group. One patient (group MA) stopped treatment after presenting with fever, exanthema, and severe arthralgia. Conclusions: Miltefosine did not present a higher cure rate than MA, and the association of GM-CSF did not improve the therapeutic response. Nevertheless, because of its less toxicity, easier administration, and a similar cure rate when compared with MA, miltefosine should remain as one of the main drugs for treating CL due to L. guyanensis.(Clinicaltrials.gov Identifier NCT03023111).

Telomere function is regulated by the telomere repeat binding proteins TRF1 and TRF2. Here the authors show that decreased levels of TRF1 proteins at shortened telomeres in aged human cells results in persistent telomere cohesion, protecting from premature senescence.

To engage students with academic research is recognised as a high-impact activity that supports the development of valuable critical thinking skills. Various approaches have been developed to promote student research both in and outside the curriculum. By incorporating the perspectives of both students and academics, this qualitative study evaluates the extent to which a research partnership is formed through an institutional research scheme called the Junior Research Associate. Our findings indicate that it is critical to move beyond the entrenched academic hierarchies of supervisor/supervisee to develop a negotiated research relationship. Challenges identified include the short timeframe to establish the conditions for successful partnership and differential expectations of partners at the outset of the scheme. It is also important to safeguard against such initiatives being instrumentalised by academics seeking to further their personal research agenda. The findings help to inform strategies to scale up such initiatives.

Background: Evidence is required to guide the redesign of health care for older people who require hospital admission. Objectives: We assessed the clinical effectiveness and cost-effectiveness of geriatrician-led admission avoidance hospital at home with comprehensive geriatric assessment, the experiences of older people and their caregivers, and how the services differed. Design: A multisite, randomised, open trial of comprehensive geriatric assessment hospital at home, compared with admission to hospital, using a 2 : 1 (hospital at home to hospital) ratio, and a parallel economic and process evaluation. Participants were randomised using a secure online system. Setting: Participants were recruited from primary care or acute hospital assessment units from nine sites across the UK. Participants: Older people who required hospital admission because of an acute change in health. Intervention: Geriatrician-led admission avoidance hospital at home with comprehensive geriatric assessment. Main outcome measures: The main outcome, ‘living at home’ (the inverse of death or living in a residential care setting), was measured at 6-month follow-up. Secondary outcomes at 6 months were the incidence of delirium, mortality, new long-term residential care, cognitive impairment, ability to perform activities of daily living, quality-adjusted survival, length of stay and transfer to hospital. Secondary outcomes at 12 months were living at home, new long-term residential care and mortality. Results: Participants were allocated to hospital at home (n = 700) or to hospital (n = 355). All reported relative risks (RRs) were adjusted and are reported for hospital at home compared with hospital. There were no significant differences between the groups in the proportions of patients ‘living at home’ at 6 months [528/672 (78.6%) vs. 247/328 (75.3%), RR 1.05, 95% confidence interval (CI) 0.95 to 1.15; p = 0.36] or at 12 months [443/670 (66.1%) vs. 219/325 (67.4%), RR 0.99, 95% CI 0.89 to 1.10; p = 0.80]; mortality at 6 months [114/673 (16.9%) vs. 58/328 (17.7%), RR 0.98, 95% CI 0.65 to 1.47; p = 0.92] or at 12 months [188/670 (28.1%) vs. 82/325 (25.2%), RR 1.14, 95% CI 0.80 to 1.62]; the proportion of patients with cognitive impairment [273/407 (67.1%) vs. 115/183 (62.8%), RR 1.06, 95% CI 0.93 to 1.21; p = 0.36]; or in ability to perform the activities of daily living as measured by the Barthel Index (mean difference 0.24, 95% CI –0.33 to 0.80; p = 0.411; hospital at home, n = 521 patients contributed data; hospital, n = 256 patients contributed data) or Comorbidity Index (adjusted mean difference 0.0002, 95% CI –0.15 to 0.15; p = 0.10; hospital at home, n = 474 patients contributed data; hospital, n = 227 patients contributed data) at 6 months. The varying denominator reflects the number of participants who contributed data to the different outcomes. There was a significant reduction in the RR of living in residential care at 6 months [37/646 (5.7%) vs. 27/311 (8.7%), RR 0.58, 95% CI 0.45 to 0.76; p

Assessment feedback should be an integral part of learning in higher education, but students can find this process emotionally and cognitively challenging. Instructors need to consider how to manage students’ responses to feedback so that students feel capable of improving their work and maintaining their wellbeing. In this paper, we examine the role of instructor-student relational feed-forward, enacted as a dialogue relating to ongoing assessment, in dissipating student anxiety, enabling productive learning attitudes and behaviours, and supporting wellbeing. We undertook qualitative data collection within two undergraduate teaching units that were adopting a relational feed-forward intervention over the 2019–2020 academic year. Student responses were elicited via small group, semi-structured interviews and personal reflective diaries, and were analysed inductively using thematic analysis. The results demonstrate that relational feed-forward promotes many elements of student feedback literacy, such as appreciating the purpose and value of feedback, judging work against a rubric, exercising volition and agency to act, and managing affect. Students were keen for instructors to help them manage their emotions related to assessment, believing this would promote their wellbeing. We conclude by exploring academic strategies and pedagogies that position relational instructor feed-forward as an act of care, and we summarize the key characteristics of emotionally resonant relational feed-forward meetings.

Collegiality and the contribution to the sustenance of the academy through academic citizenship are central to commonly held conceptions of what it is to be a university. This study investigates the articulation and recognition of academic citizenship through institutional promotion criteria, including both traditional research and teaching-focussed career pathways. The study adopts a qualitative research approach and examines promotion criteria from a sample of 55 mid-sized universities in the UK. Findings point to a progressive shift in formal recognition of service activities associated with citizenship as part of the core academic workload. Institutional service is pervasive across all academic roles and levels, student service is largely invisible, and activities associated with public service are most notably acknowledged in traditional academic roles at the professorial level. The evolving nature of expectations of citizenship necessitates a more nuanced consideration of the core dimensions of an academic role and citizenship activities to ensure equity and inclusivity in career progression.

Abstract Background A key challenge for most systems is how to provide effective access to urgent and emergency care across rural and urban populations. Tensions about the placement and scope of hospital emergency services are longstanding in Irish political life and there has been recent reform to centralise hospital services in some regions. The focus of this paper is a system approach to examine the geographic variation in resourcing and utilisation of such care across GP practices, out-of-hours care, ambulance services, Emergency Departments and Local Injury Units in Ireland. Methods We used a cross-sectional study design to evaluate variation in resource allocation by aggregating geographic funding to various elements of the urgent and emergency care system and assessing patterns in hospital resource utilisation across the population. Expenditure, staffing, access and activity data were gathered from government sources, individual facilities and service providers, health professional bodies, private firms and central statistics. Data on costs and activity in 2014 are collated and presented at both county and regional levels. Analyses focus on resources spent on urgent and emergency care across geographic areas, the role of population concentration in allocation, the relationship between pre-hospital spending and in-hospital spending, and the utilisation of hospital-based emergency care resources by residents of each county. Results An array of funding mechanisms exists, resulting in a fragmented approach to the resourcing of urgent and emergency care. There are large differences in spending per capita at the county-level, ranging from between €50 and €200 per capita; however, these are less pronounced regionally. Distribution of hospital emergency care resources is highly skewed to the North East of the country, and away from the recently reconfigured South and Mid-West regions. Conclusions This analysis advances the traditional approach of evaluating individual services or hospital resourcing. There are notable differences in utilisation of hospital-based emergency care resources at the regional level, indicating that populations within those regions which have been reconfigured have lower utilisation of hospital resources. There is a clear case for more integration in decision-making around funding and consideration of key principles, such as equity, to guide that process.

Abstract Background Group A Streptococcal (GAS) infections cause the autoimmune disease acute rheumatic fever (ARF), which can progress to chronic rheumatic heart disease (RHD). Treating pharyngitis caused by GAS with antibiotics is important in preventing ARF. However, it is difficult to distinguish these infections from GAS carriers. There is growing evidence for GAS skin infections as a cause of ARF. This study will identify the incidence of true GAS pharyngitis and serological responses to GAS skin infections. The effectiveness of antibiotics for these conditions will be explored, and modifiable risk factors. Serum antibody titres indicating the upper limits of normal (ULN for ASO/ADB antibodies) will be established alongside carriage rates in asymptomatic children. Methods This is a prospective disease incidence study, with an associated case-control study. The study population includes 1000 children (5–14 years) from Auckland, New Zealand, 800 of whom have visited their healthcare professional, resulting in a throat or skin swab for GAS, and 200 who are asymptomatic. The conditions of interest are GAS throat swab positive pharyngitis (n = 200); GAS carriage (n = 200); GAS negative throat swab (n = 200); GAS skin infections (n = 200); and asymptomatic controls (n = 200). All participants, except asymptomatic controls, will have acute and convalescent serological testing for ASO/ADB titres (collected

Background: While many public pharmacy schools have an adjoining health-system to accommodate their students, some pharmacy programs form partnerships with non-affiliated health-systems to precept students. These health-systems often afford students the opportunity to complete multiple rotations within a single organization, offering decreased onboarding time and more longitudinal experiences. Innovation: Two autonomous partnerships were developed with independent healthcare systems for concentrated learning experiences during the advanced pharmacy practice experiences year. Each program differs in student requirements and is overseen by the practice site, with participation by area faculty. Key Findings: A survey assessed professional skill set development, achievement of program goals during the experiential year, and student satisfaction of a concentrated learning experience. A comparison between programs was completed to assess for consistency in student experiences. Nineteen students (83%) responded to the survey. Students from both health-systems reported similarities in professional skill growth. Likewise, all students reported achievement of program goals and overall satisfaction with their experiential training. Conclusions: Independently managed concentrated learning experiences provided evidence of consistent growth in student professional development and achievement of programmatic goals. Partnerships with non-affiliated healthcare systems can provide a rich training ground for student learners.

Summative assessments tend to be viewed as high-stakes episodes by students, directly exposing their capabilities as learners. As such, receiving feedback is likely to evoke a variety of emotions that may interact with cognitive engagement and hence the ability to learn. Our research investigated the emotions experienced by undergraduate students in relation to assessment feedback, exploring if these emotions informed their learning attitudes and behaviours. Respondents were drawn from different years of study and subject/major. A qualitative approach was adopted, using small group, semi-structured interviews and reflective diaries. Data were analysed thematically and they revealed that receiving feedback was inherently emotional for students, permeating their wider learning experience positively and negatively. Many students struggled to receive and act upon negative feedback, especially in early years, when it was often taken personally and linked to a sense of failure. Negative emotional responses tended to reduce students’ motivation, self-confidence, and self-esteem. Some students, especially in later years of study, demonstrated resilience and engagement in response to negative feedback. By contrast, positive feedback evoked intense but fleeting emotions. Positive feedback made students feel cared about, validating their self-worth and increasing their confidence, but it was not always motivational. The paper concludes with recommendations for instructors, highlighting a need to communicate feedback carefully and to develop student and staff feedback literacies.

The “Laser-hybrid Accelerator for Radiobiological Applications,” LhARA, is conceived as a novel, flexible facility dedicated to the study of radiobiology. The technologies demonstrated in LhARA, which have wide application, will be developed to allow particle-beam therapy to be delivered in a new regimen, combining a variety of ion species in a single treatment fraction and exploiting ultra-high dose rates. LhARA will be a hybrid accelerator system in which laser interactions drive the creation of a large flux of protons or light ions that are captured using a plasma (Gabor) lens and formed into a beam. The laser-driven source allows protons and ions to be captured at energies significantly above those that pertain in conventional facilities, thus evading the current space-charge limit on the instantaneous dose rate that can be delivered. The laser-hybrid approach, therefore, will allow the radiobiology that determines the response of tissue to ionizing radiation to be studied with protons and light ions using a wide variety of time structures, spectral distributions, and spatial configurations at instantaneous dose rates up to and significantly beyond the ultra-high dose-rate “FLASH” regime. It is proposed that LhARA be developed in two stages. In the first stage, a programme of in vitro radiobiology will be served with proton beams with energies between 10 and 15 MeV. In stage two, the beam will be accelerated using a fixed-field alternating-gradient accelerator (FFA). This will allow experiments to be carried out in vitro and in vivo with proton beam energies of up to 127 MeV. In addition, ion beams with energies up to 33.4 MeV per nucleon will be available for in vitro and in vivo experiments. This paper presents the conceptual design for LhARA and the R&D programme by which the LhARA consortium seeks to establish the facility.

The International Multimorbidity Symposium was held in November 2019 at Western University to achieve three main objectives: to discuss progress and findings from various jurisdictions; to facilitate collaboration through group discussion to identify strategies to move multimorbidity research forward; and to create concrete plans to ensure advances in multimorbidity research and knowledge can be achieved through cross-national partnership. This event included keynote presentations, elevator pitch presentations and breakout sessions and there was a total of 35 attendees from eight countries, representing diverse disciplines and training levels. The overall themes arising from the event were: the importance of integrating the study and management of multimorbidity from both the primary care and public health perspectives; meaningful engagement and collaboration with patients and caregivers to understand key dimensions of multimorbidity; the considerable benefit of collaborative international partnerships; and the need to spread and scale innovations for health care systems that can better respond to the complex needs of patients and caregivers who are living with multimorbidity. Finally, it was well-acknowledged among the attendees that expanding the collaboration and discussion among international colleagues via in-person and virtual events will be important to move multimorbidity research forward.

Abstract Background Patient self-management support is recognised as a key component of chronic care. Education and training for health professionals has been shown in the literature to be associated with better uptake, implementation and effectiveness of self-management programs, however, there is no clear evidence regarding whether this training results in improved health outcomes for patients with chronic conditions. Methods A systematic review was undertaken using the PRISMA guidelines using the Cochrane Library, PubMEd, ERIC, EMBASE, CINAHL, PsycINFO, Web searches, Hand searches and Bibliographies. Articles published from inception to September 1st, 2013 were included. Systematic reviews, Meta-analysis, Randomized controlled trials (RCTs), Controlled clinical trials, Interrupted time series and Controlled before and after studies, which reported on primary care health professionals’ continuing education or evidence-based medicine/education on patient self-management for any chronic condition, were included. A minimum of two reviewers participated independently at each stage of review. Results From 7533 abstracts found, only two papers provided evidence on the effectiveness of self-management education for primary healthcare professionals in terms of measured outcomes in patients. These two articles show improvement in patient outcomes for chronic back pain and diabetes based on RCTs. The educational interventions with health professionals spanned a range of techniques and modalities but both RCTs included a motivational interviewing component. Conclusions Before and up to 2 years after the incorporation of patient empowerment for self-management into the WONCA Europe definition of general practice, there was a scarcity of high quality evidence showing improved outcomes for patients as a result of educating health professionals in patient self-management of chronic conditions.

Tankyrase 1 and 2 are poly(ADP-ribose) polymerases that mark proteins for degradation, but there is a current lack of knowledge about their distinct functions and substrates. Here, the authors elucidate the cellular roles and substrates of these polymerases using comparative functional and proteomics analyses of tankyrase knockout cell lines.

The ability to transfer learning to new situations lies at the heart of lifelong learning and the employability of university graduates. Because students are often unaware of the importance of learning transfer and staff do not always explicitly articulate this expectation, this article explores the idea that metacognition (intentional awareness and the use of that awareness) might enhance the development of learning transfer. Our exploratory study includes results from a survey of 74 staff and 118 students from five institutions in Australia, Belgium, UK, and USA. Our data indicate that many staff and a majority of students do not have a clear understanding of what learning transfer entails, and that there are many mismatches between staff and student perceptions, attitudes, and behaviors regarding learning transfer. This helps explain why learning transfer does not occur as often as it could. We found significant positive correlations between thinking about transfer and thinking about learning processes and the likelihood to use awareness of metacognition to guide practice. Our findings suggest a positive relationship between metacognition and learning transfer. Implications for the scholarship of teaching and learning are discussed.

As staff-student partnership activity becomes embedded into the infrastructure of higher education, there is an increased institutional focus on systematising the staff-student partnership support processes. Drawing on data from a case study of a partnership conceived under the auspices of an institutional staff-student partnership programme, this article offers insight into how the institutional context shapes partnership aims, objectives, and composition. It finds that in the pre-partnership phase a gatekeeping role is performed by the institutional programme, which ultimately determines which partnerships proceed and how they are evaluated. The study contributes to the broader critique of staff-student partnership practices, proposing a framework that integrates the various institutional influences and the pre- and post-partnership phases.

Network Text Analysis (NTA) is a term used to describe a variety of software - supported methods for modeling texts as networks of concepts. In this study we apply NTA to the screenplay of American Sniper, an Academy Award nominee for Best Adapted Screenplay in 2014. Specifically, we est ablish prior expectations as to the key themes associated with war films. We then empirically test whether words associated with the most influentially - positioned nodes in the network signify themes common to the war - film genre. As predicted, we find tha t words and concepts associated with the least constrained nodes in the text network were significantly more likely to be associated with the war genre and significantly less likely to be associated with genres to which the film did not belong.

Abstract Background: In the past two decades, a new epidemiological profile of Chagas’ disease (CD) has been registered in the Brazilian Amazon where oral transmission has been indicated as responsible for the increase of acute cases. In the Amazonas state, five outbreaks of acute CD have been registered since 2004. The cardiac manifestations in these cases may be characterized by diffuse myocarditis, with alteration in the electrocardiogram (ECG) and transthoracic echocardiogram (TTE). Objective: To perform a cardiac evaluation in autochthonous patients in the acute phase and at least one year after submitted to treatment for acute CD and evaluate the demographic variables associated with the presence of cardiac alterations. Methods: We evaluated patients diagnosed with acute CD through direct parasitological or serological (IgM) methods from 2007 to 2015. These patients were treated with benznidazole and underwent ECG and TTE before and after treatment. We assumed a confidence interval of 95% (CI 95%, p < 0.05) for all variables analyzed. Results: We observed 63 cases of an acute CD in which oral transmission corresponded to 75%. Cardiac alterations were found in 33% of the cases, with a greater frequency of ventricular repolarization alteration (13%), followed by pericardial effusion (10%) and right bundle branch block and left anterior fascicular block (2%). The follow-up occurred in 48 patients with ECG and 25 with TTE for a mean period of 15.5 ± 4.1 months after treatment. Of these, 8% presented normalization of the cardiac alterations in ECG, 62.5% remained with the normal exams. All of the patients presented normal results in TTE in the post-treatment period. As for the demographic variables, isolated cases presented more cardiac alterations than outbreaks (p = 0.044) as well as cases from Central Amazonas mesoregion (p = 0.020). Conclusions: Although cardiac alterations have not been frequent in most of the studied population, a continuous evaluation of the clinical-epidemiological dynamics of the disease in the region is necessary in order to establish preventive measures.